Methods and devices for repairing cartilage defects - Patents.com

Abstract

The present disclosure describes devices and methods for repairing cartilage defects using arthroscopic surgical methods. The disclosed devices include a cannula assembly including a cannula body, a dam seal subassembly disposed proximally from the cannula body, and an obturator coaxially inserted through both the cannula body and the dam seal subassembly, an articulated arthroscopic cutting tool, a ring curette, a square curette, a rake curette, a matrix shuttle delivery device (540) with at least two deployment wings (548) for delivering a cell-seeded support matrix including chondrocytes, and an applicator tool.

Description

[Background technology]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to U.S. Provisional Application No. 63 / 316,920, entitled "Methods and Devices for Repairing Cartilage Defects," filed March 4, 2022, the contents of which are incorporated by reference in their entirety into this specification.

[0002] Cartilage and osteochondral lesions, such as focal lesions in weight-bearing areas of the articular cartilage of the knee, greatly increase the risk of osteoarthritis. This type of lesion frequently arises, for example, from trauma, participation in sports, osteochondritis dissecans, etc. The natural healing capacity of cartilage lesions is minimal, due in part to the limited blood supply to the cartilage tissue. To treat damaged cartilage, it is necessary to replace the defective cartilage with healthy cartilage. And to achieve such a replacement, an autologous chondrocyte transplantation strategy has been described (Brittberg et al. Clin. Orthopaed.Red.Res. (1999) 367S: S147-S155). In such a procedure, chondrocytes are harvested from the patient, expanded in cell culture to increase the number of chondrocytes, and then transplanted back into the patient's damaged area.

[0003] More recent studies have improved autografting by seeding autologous cells grown on a matrix in a process known as matrix-induced autologous chondrocyte implantation (MACI) (Basad et al. In: Hendrich et al., Cartilage Surgery and Future Perspectives, Thieme Verlag, 49-56 (2003)). The MACI process has been further improved to allow for the implantation of allogeneic cells, reducing the total number of procedures a patient needs to undergo. However, MACI procedures have typically been performed through an open surgical technique called a mini-arthrotomy, which generally exposes patients to a higher risk of infection, longer recovery times, and greater pain compared to less invasive surgical techniques. Additionally, many patients present with defects that are amenable to treatment through minimally invasive procedures. [Prior art documents] [Non-patent literature]

[0004] [Non-Patent Document 1] Brittberg et al. Clin. Orthopaed. Red. Res. (1999) 367S: S147-S155 [Non-Patent Document 2] Basad et al. In: Hendrich et al., Cartilage Surgery and Future Perspectives, Thieme Verlag, 49-56 (2003) Summary of the Invention [Means for solving the problem]

[0005] The present disclosure provides improved matrix-induced chondrocyte transplantation techniques. For example, among other things, the present disclosure provides techniques for arthroscopic delivery of MACI implants. In some embodiments, the provided techniques are characterized by achieving delivery characterized by levels of cell viability comparable to those observed with non-arthroscopic delivery. Advantages of the provided methods include, for example, arthroscopic delivery, which is much less invasive than the open surgical strategies typically used to administer MACI implants. Thus, the provided techniques represent and embody further improvements regarding arthroscopic MACI techniques (tools, methods, and kits) for the treatment of tissue defects (e.g., cartilage defects, among other types of defects).

[0006] In some embodiments, the present disclosure provides techniques for arthroscopically delivering a composition comprising cells seeded on the surface of a matrix to the site of an articulating joint.

[0007] In some embodiments, the present disclosure provides techniques for treating cartilage and / or osteochondral defects. The methods may include implanting a composition comprising cells seeded on a matrix.

[0008] In some embodiments, the present disclosure provides arthroscopic delivery techniques and methods. In general, the present disclosure provides a set of tools and methods that allow for arthroscopic delivery of cell-seeded implants at treated cartilage surgical sites to effectively repair cartilage and tissue defects in a less invasive manner than traditional open surgical procedures while maintaining cell viability.

[0009] In some embodiments, the present disclosure provides techniques for arthroscopically treating cartilage defects or lesions, which may include one or more surgically sharp cutting tools for defining a surgical field in the cartilage, scraping, cutting, debridement, and / or removing the cartilage.

[0010] In some embodiments, a composition comprising cells seeded on a matrix (or cell-seeded support matrix) is loaded into the distal end of the surgical shuttle delivery device prior to insertion of the surgical shuttle delivery device into a cannula placed at the surgical site. The composition can then be deposited from the surgical shuttle delivery device into the surgical area that has been previously prepared by a surgically sharp cutting tool.

[0011] In some embodiments, the cells are in a monolayer on the membrane.

[0012] In some embodiments, the cell-seeded support matrix is ​​cut into a shape and size that closely matches the shape and size of the treated surgical area by a surgically sharp cutting tool. The present disclosure provides a method of cutting the cell-seeded support matrix using a matrix cutting tool. In some embodiments, the matrix cutting tool can have a defined shape (e.g., oval, circle, square, rectangle, etc.) along the bottom periphery and a surgically sharp blade. The matrix cutting tool can be placed blade-side down on a portion of the cell-seeded support matrix and pressed down with force exerted by hand or a tool (e.g., hammer, mallet, etc.) to cut into the cell-seeded support matrix. In some embodiments, the cut portion of the cell-seeded support matrix can be manipulated (e.g., picked up, positioned, placed, etc.) using a tool (e.g., tweezers, grasper, probe, etc.) or by hand.

[0013] In some embodiments, the present disclosure provides a method of arthroscopically delivering a composition comprising cells seeded on a surface of a matrix (or cell-seeded support matrix) to a defect, the defect comprising a knee defect, such as a femoral defect, a trochlear defect, a patella defect, and / or a tibial defect, in a subject. In some embodiments, the defect may comprise an ankle defect and / or a shoulder defect. The defect may be up to about 4 cm 2In some embodiments, the method includes steps performed within a period from surgical opening to surgical closure, the period not exceeding about 60 minutes. In some embodiments, the defect comprises a cartilage defect. In some embodiments, the cells comprise chondrocytes. In some embodiments, the cells are autologous to the subject. In some embodiments, the cells comprise allogeneic cells.

[0014] In some embodiments, the surgical instrument system includes a cannula assembly, a composition including cells seeded on the surface of the matrix (or cell-seeded support matrix), and one or more cutting tools for cutting and shaping the composition. The kit may also include one or more of the following tools constructed to pass through the cannula to perform arthroscopic procedures: an arthroscopic measurement tool, a multi-joint cutting tool, a ring curette, a square curette, a rake curette, an applicator tool, and a matrix shuttle delivery device for transporting and depositing the composition at the surgical site. In some embodiments, the user or operator or surgeon may use other surgical tools and materials during the arthroscopic surgical procedure, which may include hemostatic barriers, cover patches, organic adhesives, scissors, razor blades, scalpels, surgical mallets, tweezers, needles, etc.

[0015] In some embodiments, the cannula assembly may include an obturator, a dam seal subassembly, and a cannula body. The dam seal subassembly may be released from the cannula body via a clip or tab. A flexible dam seal in the dam seal subassembly may allow surgical tools to be inserted into the cannula while retaining fluids within the surgical site or joint area of ​​the patient. The cannula body may be threaded along its exterior surface to improve its stability when placed at the surgical site.

[0016] In some embodiments, the arthroscopic measurement tool may include a handle, a shaft, a flexible ruler, and / or an adjustment knob. The flexible ruler is etched or marked with millimeter-scale marks and is connected to the adjustment knob such that sliding the knob longitudinally along the handle extends or retracts the ruler and rotating the knob rotates the ruler to different orientations or angles. The ruler can be used to measure the dimensions of the cartilage defect.

[0017] In some embodiments, the articulated arthroscopic cutting tool may include a handle, a thumb slider, a shaft, and / or a curved oval blade with a surgically sharp cutting edge. When the thumb slider is slid, the blade is inclined at various angles relative to the longitudinal axis of the handle and shaft. The blade may be pressed or jammed into the cartilage surrounding the cartilage defect with a surgical mallet to score the cartilage. The cartilage score forms a well-defined outline to define the area where the cartilage should be removed in preparation for implantation of a cell-seeded support matrix. In some embodiments, the curved oval blades created may include various sizes to surround different sized cartilage defects. The articulated arthroscopic cutting tool may also be referred to as an arthroscopic cutter.

[0018] In some embodiments, the ring curette may include a handle, a shaft, and / or a circular ring having a surgically sharp cutting edge.

[0019] In some embodiments, a square curette may include a handle, a shaft, and / or a square ring having at least two surgically sharp cutting edges.

[0020] In some embodiments, a rake curette may include a handle, a shaft, and / or a wedge-shaped blade having a surgically sharp cutting edge.

[0021] In some embodiments, the matrix cutter may include an elliptical cylindrical body and / or a surgically sharp edge on its bottom periphery. In some embodiments, the matrix cutter may include a variety of sizes to match the size of the curved elliptical blade in the articulated arthroscopic cutting tool. The matrix cutter is used to cut a portion of the cell-seeded support matrix into a shape that fits the cartilage defect site treated by the cutting tool while minimizing contact and damage to the cells.

[0022] In some embodiments, the matrix shuttle delivery device may include a cylindrical body with finger grips and a tapered delivery tip, a plunger, and deployment wings. A portion of the cell-seeded support matrix may be placed on the matrix shuttle delivery device, which may then be inserted into a cannula at the surgical site or joint. When the plunger is pressed, the deployment wings protrude at the delivery tip, pushing the cell-seeded support matrix out of the matrix shuttle delivery device and onto the defect site.

[0023] In some embodiments, the applicator tool may include a cylindrical rod, an applicator swab at one end of the rod, and / or an applicator tip at the other end of the rod. The applicator swab may include one or more flexible absorbent materials including polyurethane foam and cotton and may be used to clean and dry the defect site. The applicator tip may include silicone or other similar elastic polymeric material. The applicator tip may be used to reposition the cell-seeded support matrix and apply fibrin glue.

[0024] In one aspect, the present embodiment is directed to a cannula assembly comprising a cannula body, a dam seal subassembly disposed proximally from the cannula body, where the dam seal subassembly and the cannula body are coaxially aligned (or longitudinally aligned or axially aligned), and an obturator coaxially inserted through both the cannula body and the dam seal subassembly.

[0025] In some embodiments, the cannula body includes a hollow cylindrical portion including a helical thread wrapping around the entire length of an outer surface of the hollow cylindrical portion, a lip portion at a proximal end of the hollow cylindrical portion, the lip portion including a diameter larger than a diameter of the hollow cylindrical portion, two tabs positioned diametrically opposite each other on an outer edge of the lip portion, and a curved opening at a distal end of the hollow cylindrical portion.

[0026] In some embodiments, the curved opening is marked by a visible outline around the periphery of the curved opening and by two small visible marks diametrically opposed to each other around the curved opening.

[0027] In some embodiments, the cannula body comprises a translucent polycarbonate material.

[0028] In some embodiments, the dam seal subassembly comprises a dam top piece, a first dam seal including at least one hole, a second dam seal including at least one slit, a third dam seal including at least one slit, and a dam bottom piece, In some embodiments, the dam top piece, the first dam seal, the second dam seal, and the third dam seal are all coaxially aligned (or longitudinally aligned or axially aligned) and stacked parallel to one another.

[0029] In some embodiments, the dam top piece includes a circular portion including a circular hole concentrically disposed therein, a plurality of legs extending perpendicularly from a bottom surface of the circular portion and distributed circumferentially around the circular portion, and two notches disposed diametrically opposite each other around the circular hole.

[0030] In some embodiments, the dam top piece and the dam bottom piece comprise acrylonitrile butadiene styrene (ABS).

[0031] In some embodiments, the first dam seal comprises a circular disk, a circular hole concentrically disposed at the center of the circular disk, and a plurality of smaller circular holes circumferentially disposed around the edge of the disk.

[0032] In some embodiments, the second dam seal and the third dam seal each comprise a circular disk, three slits separated from each other by 120 degrees along a radial direction from a center of the circular disk, and a plurality of smaller circular holes arranged circumferentially around an edge of the circular disk, hi some embodiments, the second dam seal and the third dam seal are stacked coaxially on top of each other and rotated such that the slits of each seal do not overlap.

[0033] In some embodiments, the first dam seal, the second dam seal, and the third dam seal all comprise one of a silicone rubber or an EPDM rubber.

[0034] In some embodiments, the dam bottom piece comprises a hollow cylindrical portion, a flat circular top, a circular hole concentrically disposed in the flat circular top, two recesses diametrically disposed around the circular hole, and two dam release clips diametrically disposed on a distal edge of the hollow cylindrical portion.

[0035] In some embodiments, the dam top piece and the dam bottom piece comprise acrylonitrile butadiene styrene (ABS) or the like.

[0036] In some embodiments, the obturator comprises a handle portion at a proximal end of the obturator, a shaft portion, and a tip at a distal end of the obturator, in some embodiments, the handle portion comprises a rounded dome structure including slats of constant thickness arranged axially parallel and perpendicular, the shaft portion comprises a cylindrical rod connecting the handle portion and the tip, the tip portion comprises a conical tip and a number of support fins at a distal end, and the handle portion, shaft portion, and tip are all coaxially aligned (or longitudinally aligned, or axially aligned).

[0037] In some embodiments, the obturator includes two or more rotation tabs protruding from the bottom distal side of the handle portion diametrically opposed to one another, and one or more concave portions in the dome-shaped structure of the handle portion.

[0038] In some embodiments, the obturator comprises acrylonitrile butadiene styrene (ABS) or the like.

[0039] In another aspect, the present embodiments are directed to an arthroscopic surgical method including making an incision in a joint of a patient's body, inserting a cannula assembly into the incision, measuring a cartilage defect in the joint using an arthroscopic measurement tool inserted through the cannula, preparing a cartilage area surrounding the cartilage defect, and preparing and cutting a portion of the cell-seeded matrix composition using a matrix cutter tool.

[0040] In some embodiments, treating the cartilage region further includes scoring an area of ​​cartilage around the defect using a cutter tool, debriding the scored area using one or more cutting and scraping tools to expose a bone surface in a defined area or shape, and drying the exposed bone area using an applicator tool.

[0041] In some embodiments, the joint site may include one of the medial femoral condyle, the lateral femoral condyle, the patella, or the trochlea.

[0042] In some embodiments, debriding the incision area further comprises using at least one of a ring curette, a square curette, or a rake curette.

[0043] In another aspect, the present embodiments are directed to a method for determining a size of a lesion during arthroscopic surgery, the method including inserting a measurement tool into a cannula through a dam seal subassembly, extending a ruler from the measurement tool, measuring at least one dimension of at least one lesion using at least one or more marks on the ruler, retracting the ruler into the measurement tool, and removing the measurement tool from the cannula and the dam seal subassembly.

[0044] In another aspect, the present embodiments are directed to an arthroscopic measurement probe, the arthroscopic measurement probe including a handle including a top shell piece and a bottom shell piece, an adjustment knob, a rotating plug, a dowel pin, a stroke arm, a sizer tube, and a flexible ruler. In some embodiments, the rotating plug, the adjustment knob, the stroke arm, the sizer tube, and the flexible ruler are coaxially connected, and the flexible ruler is disposed through an interior of the sizer tube.

[0045] In some embodiments, the flexible ruler comprises a cylindrical rod comprising polyetheretherketone (PEEK), an inner flexible wire comprising nickel titanium (or nitinol), and a plurality of marks distributed along the length of the outer surface of the cylindrical rod near the distal end of the cylindrical rod. In some embodiments, the marks comprise thin lines perpendicular to the longitudinal axis of the cylindrical rod and spaced at intervals of 2.5 mm and 5.0 mm.

[0046] In some embodiments, the sizer tube comprises a hollow cylindrical tube comprising at least one of stainless steel T304, stainless steel T316, and fractional hypodermic tubing, two slits disposed diametrically opposite each other at a proximal end of the hollow cylindrical tube, and a curved portion of the hollow cylindrical tube at a distal end, In some embodiments, the curved portion comprises a right angle bend in the tube and an opening at the distal end of the hollow cylindrical tube.

[0047] In some embodiments, the top and bottom shell pieces comprise acrylonitrile butadiene styrene (ABS) or other similar plastic.

[0048] In another aspect, the present embodiments are directed to a method for scoring cartilage using an articulated arthroscopic cutting tool, the method including selecting an articulated arthroscopic cutting tool based on measured dimensions of a defect or lesion, removing a dam seal subassembly from a cannula, inserting the articulated arthroscopic cutting tool into the cannula, adjusting the bevel angle of the blade using a thumb slider, locking the bevel angle, forcing the blade into the cartilage area surrounding the defect, and removing the articulated arthroscopic cutting tool from the cannula.

[0049] In another aspect, the present embodiments are directed to an articulated arthroscopic cutting tool that includes a handle, a thumb slider, a linear stator shaft, a curved elliptical blade connected to the linear stator shaft by a hinge joint, a linear transmission shaft connected to the thumb slider, and a link piece connected to both the linear transmission shaft and the curved elliptical blade. In some embodiments, movement of the thumb slider causes the curved elliptical blade to tilt relative to the linear stator shaft.

[0050] In some embodiments, the handle includes an upper shell including a barbed semi-cylinder and a rectangular opening cut longitudinally along the barbed semi-cylinder near a distal end of the barbed semi-cylinder, and a lower shell including the barbed semi-cylinder, In some embodiments, the upper and lower shells are closed together to form a complete cylinder with a circular opening at the distal end, and a plurality of notches are disposed on the underside of the upper shell around the rectangular opening.

[0051] In some embodiments, the upper and lower shells comprise acrylonitrile butadiene styrene (ABS) or an equivalent plastic.

[0052] In some embodiments, the thumb slider comprises a slide button including a raised top surface at a distal end of the button and a protruding top surface at a proximal end of the button, a slider clamp piece, and a spring attached at one end of the spring to the slide button and at another end of the spring to the slider clamp piece, the spring being disposed vertically between the slide button and the slider clamp piece. In some embodiments, a cylindrical pin actuated by the slide button may interface with a number of notches in the underside of the top shell.

[0053] In some embodiments, the linear stator shaft comprises a cylindrical rod, a rectangular groove cut longitudinally along the cylindrical rod, a reduced diameter portion along the cylindrical rod near its proximal end, and a circular ring protruding perpendicularly from the distal end of the cylindrical rod.

[0054] In some embodiments, the linear stator shaft comprises stainless steel type 17-4PH(630), UNS S17400, conforming to ASTM A564.

[0055] In some embodiments, the curved elliptical blade comprises an elliptical ring, at least three crossbar pieces extending across a top surface of the elliptical ring, a circular ring extending perpendicularly from a first crossbar piece, two circular rings extending perpendicularly from a second crossbar piece, and a curved cutting surface along a bottom periphery of the elliptical ring, wherein the elliptical ring is thicker at a narrow end of the elliptical ring, and the curved cutting surface includes a surgically sharp edge.

[0056] In some embodiments, the curved oval blade comprises stainless steel type 17-4PH(630), UNS S17400, conforming to ASTM A564.

[0057] In another aspect, the present embodiments are directed to a method of removing cartilage and preparing a surgical site comprising inserting a surgical cutting tool selected from at least one of a ring curette, a square curette, or a rake into a cannula and dam seal subassembly; scraping, cutting, debriding and removing cartilage within the area of ​​cartilage defined by the arthroscopic cutting tool using the surgical cutting tool; removing the cutting tool from the cannula and dam seal subassembly; and repeating the procedure with one or more surgical cutting tools until all of the cartilage within the area of ​​cartilage is removed.

[0058] In another aspect, the present embodiments are directed to a ring curette assembly comprising a handle, a shaft coupled to a distal end of the handle, and a ring curette blade coupled to the distal end of the shaft, wherein the shaft comprises a cylindrical rod having at least two bends such that the distal end of the shaft has an axis parallel to and eccentric from a main longitudinal axis of the shaft, and the ring curette blade has at least one surgically sharp edge.

[0059] In some embodiments, the shaft includes a cylindrical rod, a flat portion at a proximal end of the cylindrical rod for mounting within the handle, a first bend in the cylindrical rod near the distal end of the rod such that the rod axis is angled away from a main longitudinal axis of the cylindrical rod, a second bend in the cylindrical rod near the further distal end of the rod such that the rod axis is angled parallel to and eccentrically disposed from the main longitudinal axis of the cylindrical rod, a cylindrical portion of reduced diameter near the distal end of the rod, and a concave opening at the distal end of the shaft having a flat inner surface.

[0060] In some embodiments, the ring curette blade includes a hollow frustoconical ring, a rounded edge around a larger periphery of the ring, a surgically sharp edge around the larger periphery of the ring, a cylindrical connecting shaft disposed radially outwardly at an outer wall of the ring, and a cylindrical welding shaft disposed coaxially with the connecting shaft. In some embodiments, the cylindrical welding shaft is smaller in diameter than the cylindrical connecting shaft.

[0061] In some embodiments, the shaft and ring curette blade comprise stainless steel type 17-4PH (630) or equivalent, conforming to ASTM A564, and / or UNS S17400.

[0062] In some embodiments, the handle comprises a cylindrical body, a number of protrusions on an outer surface and a bottom surface of the cylindrical body arranged perpendicular to a longitudinal axis of the cylindrical body, a flat surface along a top surface of the cylindrical body, and a circular opening at a distal end of the cylindrical body.

[0063] In some embodiments, the handle comprises acrylonitrile butadiene styrene (ABS) or the like.

[0064] In another aspect, the present embodiments are directed to a square curette assembly comprising a handle, a shaft coupled to a distal end of the handle, and a square curette blade coupled to the distal end of the shaft. In some embodiments, the shaft comprises a cylindrical rod having at least two bends such that the distal end of the shaft has an axis parallel to and eccentric from a major longitudinal axis of the shaft, and the square curette blade comprises at least two surgically sharp edges at the distal end of the square curette blade.

[0065] In some embodiments, the square curette blade includes a ring in the shape of a hollow rounded right-angle prism, at least two surgically sharp edges at the top and bottom edges of the ring distal to the right-angle prism, a cylindrical connecting shaft facing outwardly at the outer wall of the ring and positioned opposite the two surgically sharp edges, and a cylindrical welding shaft coaxially positioned with the connecting shaft. In some embodiments, the cylindrical welding shaft is smaller in diameter than the connecting shaft.

[0066] In some embodiments, the shaft and square curette blade comprise stainless steel type 17-4PH (630) or equivalent, conforming to ASTM A564, or UNS S17400.

[0067] In another aspect, the present embodiments are directed to a rake curette assembly comprising a handle, a rake shaft coupled to a distal end of the handle, and a rake head blade coupled to the distal end of the shaft. In some embodiments, the rake shaft comprises a cylindrical rod tapered to a smaller diameter near the distal end of the shaft, and the rake head blade comprises a tapered wedge having at least one surgically sharp edge.

[0068] In some embodiments, the rake shaft includes a cylindrical rod, a flat portion at a proximal end of the shaft for mounting within the handle, and a tapered portion, hi some embodiments, the diameter of the cylindrical rod gradually decreases toward the distal end of the rake shaft, and the rake further includes a cylindrical welded shaft of further reduced diameter disposed coaxially with the tapered portion of the rake shaft.

[0069] In some embodiments, the rake head blade includes a wedge-shaped body that decreases in thickness with increasing depth, a rounded top with a cylindrical opening for welding, and a surgically sharp edge at the end of the wedge-shaped body.

[0070] In some embodiments, the shaft and rake head blades comprise stainless steel type 17-4PH (630) conforming to ASTM A564 or equivalent, or UNS S17400.

[0071] In another aspect, the present embodiments are directed to a method for cutting a cell-seeded support matrix, the method including: selecting a size of matrix cutter to fit a surgical site that has been prepared by cutting and removing cartilage surrounding a defect or lesion; placing the cell-seeded support matrix on a cutting mat with the cells on the matrix facing upward; placing the selected matrix cutter on the cell-seeded support matrix with the surgically sharp edge facing downward; applying a downward force to an upper surface of the matrix cutter using at least one of a hand, a mallet, a hammer, or other tool; and removing the matrix cutter and removing the uncut portion of the cell-seeded support matrix.

[0072] In another aspect, the present embodiments are directed to a matrix cutter comprising an elliptical cylinder body, a stadium-shaped internal bore aligned parallel to a semi-major axis of the elliptical cylinder body and longitudinally aligned parallel to a longitudinal axis of the elliptical cylinder body, a flat upper surface of the elliptical cylinder body, at least two flat gripping notches on opposing exterior surfaces of the elliptical cylinder body, and a surgically sharp edge around a bottom periphery of the elliptical cylinder body.

[0073] In some embodiments, the matrix cutter comprises stainless steel type 17-4PH(630) conforming to ASTM A564 and / or UNSS17400.

[0074] In another aspect, the present embodiments provide a method for delivering and implanting a cell-seeded support matrix to a treated cartilage surgical site, comprising: stopping fluid flow and removing a dam seal subassembly at the surgical site; cleaning and drying the surgical site where cartilage had previously been cut and removed around the lesion or defect using a first applicator swab; picking up a pre-cut piece of cell-seeded support matrix using tweezers by grasping an edge of the matrix; placing the cell-seeded support matrix over a delivery tip of a matrix shuttle delivery device such that the matrix is ​​within the contour of the delivery tip and the cell-containing side of the matrix faces away from the delivery tip; and applying a second applicator swab to the surgical site. applying fibrin glue to the surgical site using a caterpillar swab; inserting a matrix shuttle delivery device into a cannula at the surgical site; depressing a plunger on the matrix shuttle device to extend at least one antenna from within a delivery tip of the matrix shuttle device to extrude and force a cell-seeded support matrix onto the surgical site; removing the matrix shuttle device from the cannula; if necessary, repositioning the cell-seeded support matrix using a third applicator swab; and applying fibrin glue around the edges of the cell-seeded support matrix at the surgical site using a fourth applicator swab.

[0075] In another aspect, the present embodiments are directed to a matrix shuttle delivery device comprising a shuttle body, the shuttle body comprising a substantially hollow cylinder, a delivery tip at a distal end of the shuttle body, a plunger disposed longitudinally within the shuttle body and protruding from a proximal end of the shuttle body, at least two deployment wings disposed within the delivery tip and attached to the plunger, and at least two holes on a distal surface of the delivery tip, wherein pressing the plunger longitudinally into the shuttle body deploys the at least two deployment wings outward through the at least two holes in the delivery tip.

[0076] In some embodiments, the matrix shuttle device further comprises a spring disposed longitudinally within the shuttle body and attached to the plunger. In some embodiments, the matrix shuttle device further comprises one or more finger grips disposed at a proximal end of the shuttle body. In some embodiments, the one or more finger grips each comprise a rod connected at one end to an outer surface of the shuttle body and extending radially outward from the shuttle body, with a distal side of each rod curved to accommodate a user's finger.

[0077] In some embodiments, the delivery tip includes a cylindrical section connected to the shuttle body at the proximal end of the delivery tip, a tapered section including two sloping sides that meet at a flat surface at the distal end of the delivery tip, and a contoured ledge around the distal end of the delivery tip that includes an elliptical or oval shape, the centerline of the contoured ledge being substantially parallel to the flat surface at the distal end of the delivery tip. In some embodiments, the at least two holes are each disposed on two sloping sides of the delivery tip such that when the deployment wings are unfurled, a line connecting the rounded tips of the deployment wings is substantially perpendicular to the flat surface at the distal end of the delivery tip. In some embodiments, the at least two holes each include a diameter that is greater than the diameter of each of the at least two deployment wings.

[0078] In some embodiments, the deployment wings comprise a U-shaped body, at least two wing arms comprising cylindrical rods extending parallel to and curving outward away from the U-shaped body, at least two rounded tips at the distal ends of the at least two wing arms, and a circular hole at the proximal bottom of the U-shaped body. In some embodiments, the deployment wings comprise at least one member from the group consisting of silicone, ethylene propylene diene monomer (EPDM) rubber, plastic, and flexible polymeric material.

[0079] In some embodiments, the plunger comprises a cylindrical body, a flat disk portion at the proximal end of the cylindrical body, a recess with a protruding pin at the proximal end of the cylindrical body, the protruding pin comprises a small cylinder disposed perpendicular to the longitudinal axis of the cylindrical body, and a rounded knob having a diameter larger than the diameter of the small cylinder. In some embodiments, the protruding pin of the plunger passes through a circular hole in the proximal bottom of the U-shaped body of the deployment wing.

[0080] In some embodiments, the plunger and shuttle body comprise at least one of acrylonitrile butadiene styrene (ABS) or plastic. In some embodiments, the shuttle body, delivery tip, and finger grip are formed as two continuous identical shells that collectively form the matrix shuttle delivery device. In some embodiments, a spring retracts the at least two deployment wings into the at least two holes when the plunger is released.

[0081] In another aspect, the present embodiments are directed to a matrix shuttle delivery device comprising: a shuttle body, the shuttle body comprising a substantially hollow cylinder; a delivery tip at a distal end of the shuttle body, the delivery tip comprising a cylindrical portion connected to the shuttle body at a proximal end of the delivery tip, a tapered portion including two sloping sides that meet in a flat surface at the distal end of the delivery tip, and a contoured ledge across the top and distal end of the delivery tip comprising an elliptical or oval shape; and a plunger disposed longitudinally within the shuttle body and protruding from a proximal end of the shuttle body, the plunger comprising a cylindrical body, a flat disk portion at the proximal end of the cylindrical body, and a recess with a protruding pin at the proximal end of the cylindrical body, the protruding pin comprising a small cylinder disposed perpendicular to the longitudinal axis of the cylindrical body and a rounded knob having a diameter larger than the diameter of the small cylinder.

[0082] In some embodiments, the matrix shuttle delivery device further comprises at least two deployment wings disposed within the delivery tip and attached to a plunger, the deployment wings comprising a U-shaped body, at least two wing arms including cylindrical rods extending parallel from the U-shaped body and curving outward away from the U-shaped body, at least two rounded tips at the distal ends of the at least two wing arms, and a circular hole at the proximal bottom of the U-shaped body; and one or more finger grips disposed at the proximal end of the shuttle body, the device further comprising at least two holes, each hole disposed on one of two slanted sides of the delivery tip; and a spring disposed longitudinally inside the shuttle body and attached to the plunger, wherein when the plunger is pressed longitudinally into the shuttle body, the at least two deployment wings exit the at least two holes in the delivery tip, and when the plunger is released, the spring retracts the at least two deployment wings into the at least two holes.

[0083] In another aspect, the present disclosure is directed to accomplishing an arthroscopic surgical method for repairing a cartilage defect, the method comprising: making an incision in a joint of a patient's body near the cartilage defect; inserting a cannula assembly into the incision; measuring the cartilage defect in the joint using an arthroscopic measurement tool inserted through the cannula; preparing the cartilage area surrounding the cartilage defect; preparing and cutting a portion of the cell-seeded matrix composition using a matrix cutter tool to match the shape of the prepared cartilage area; placing the portion of the cell-seeded matrix composition over a delivery tip of a matrix shuttle delivery device; inserting the matrix shuttle delivery device through the cannula; depressing a plunger on the matrix shuttle delivery device to deploy at least two deployment wings from within the delivery tip, thereby forcing the portion of the cell-seeded matrix composition out of the delivery tip and onto the prepared cartilage area; and removing the matrix shuttle delivery device from the cannula.

[0084] In some embodiments, treating the region of cartilage includes using a first cutting tool to define a region of cartilage surrounding the cartilage defect, and using one or more additional surgical cutting tools to scrape, cut, debride, and / or remove cartilage within the region of cartilage defined by the first cutting tool.

[0085] In some embodiments, the cell-seeded matrix composition comprises chondrocytes seeded on one side of a bioabsorbable matrix, the side of the matrix having the chondrocytes facing away from the delivery tip of the matrix shuttle delivery device.

[0086] In some embodiments, the method further includes applying a fibrin glue to the treated cartilage prior to delivery of the cell-seeded matrix composition, applying fibrin glue around the edges of the cell-seeded matrix composition after the cell-seeded matrix composition has been delivered to the treated cartilage, removing the cannula from the incision, and surgically closing the incision.

[0087] In another aspect, the present embodiments are directed to an applicator tool comprising a cylindrical rod, an applicator swab adhesively attached to one end of the cylindrical rod, and an applicator tip adhesively attached to another end of the cylindrical rod, In some embodiments, the cylindrical rod is constructed from or includes a plastic material, the applicator swab includes cotton, polyurethane foam, and / or other similarly flexible absorbent material, and the applicator tip includes a flexible silicone or other similarly flexible material.

[0088] The present teachings described herein will be more fully understood from the following description of various exemplary embodiments when read in conjunction with the accompanying drawings, in which it should be understood that the drawings described below are for illustrative purposes only and are not intended to limit the scope of the present teachings in any manner. [Brief description of the drawings]

[0089] [Figure 1] 1 shows a schematic diagram of a method of performing arthroscopic surgery according to aspects of the present embodiment;

[0090] [Figure 2A] 1 illustrates an exemplary arthroscopic surgical process, in accordance with aspects of the present embodiment;

[0091] [Figure 2B] 1 illustrates an exemplary arthroscopic surgical process, in accordance with aspects of the present embodiment;

[0092] [Figure 2C] 1 illustrates an exemplary arthroscopic surgical process, in accordance with aspects of the present embodiment;

[0093] [Figure 2D] 1 illustrates an exemplary arthroscopic surgical process, in accordance with aspects of the present embodiment;

[0094] [Figure 2E] 1 illustrates an exemplary arthroscopic surgical process, in accordance with aspects of the present embodiment;

[0095] [Figure 2F] 1 illustrates an exemplary arthroscopic surgical process, in accordance with aspects of the present embodiment;

[0096] [Diagram 3] 1A-1D show schematic diagrams of a method of using the cannula assembly during arthroscopic surgery in accordance with aspects of the present embodiment;

[0097] [Figure 4] 1 illustrates a perspective view of a cannula assembly according to aspects of the embodiment;

[0098] [Diagram 5] 13 illustrates how the obturator and dam subassembly are assembled, according to aspects of the present embodiment;

[0099] [Figure 6] 1 illustrates a perspective view of a cannula body according to aspects of the embodiment;

[0100] [Figure 7] 1 illustrates a side view of a cannula body in accordance with aspects of the embodiment;

[0101] [Figure 8] 1 illustrates a perspective view of a cannula body according to aspects of the embodiment;

[0102] [Figure 9] 1 illustrates a perspective view of a dam seal subassembly in accordance with aspects of the present embodiment;

[0103] [Figure 10] 1 illustrates an exploded perspective view of components of a dam seal subassembly in accordance with aspects of the present embodiment;

[0104] [Figure 11] 1 illustrates a perspective view of a slit dam seal in accordance with aspects of the present embodiment;

[0105] [Figure 12] 1 illustrates a perspective view of a perforated dam seal in accordance with aspects of the present embodiment;

[0106] [Figure 13] 1 illustrates a perspective view of an obturator in accordance with aspects of the present embodiment;

[0107] [Figure 14] 1 illustrates a side view of an obturator in accordance with aspects of the present embodiment;

[0108] [Figure 15] 13A-13C show diagrams of an obturator and dam seal subassembly positioned near a cannula inserted into an incision at a joint, according to aspects of the present embodiment.

[0109] [Figure 16] 1 shows a schematic diagram of a method of using an arthroscopic measurement probe, in accordance with aspects of the present embodiment;

[0110] [Figure 17] 1 illustrates a perspective view of an arthroscopic measurement probe assembly in accordance with aspects of the present embodiment;

[0111] [Figure 18] 1 illustrates an exploded perspective view of parts of an arthroscopic measurement probe assembly in accordance with aspects of the present embodiment;

[0112] [Figure 19] 1 illustrates a ruler for an arthroscopic measurement probe in accordance with aspects of the present embodiment;

[0113] [Figure 20] 1 illustrates a tube for an arthroscopic measurement probe, in accordance with aspects of the present embodiment;

[0114] [Figure 21] FIG. 13 illustrates a perspective view of an arthroscopic probe assembly with arrows indicating movement and showing the ruler deployed, in accordance with aspects of the present embodiment;

[0115] [Figure 22] 1A-1D show schematic diagrams of a method of using an articulated arthroscopic cutting tool during an arthroscopic surgical procedure, in accordance with aspects of the present embodiment;

[0116] [Figure 23] 1 illustrates a perspective view of an articulated arthroscopic cutting tool assembly in accordance with aspects of the present embodiment;

[0117] [Figure 24] 1 illustrates a perspective view of a distal end of an articulated arthroscopic cutting tool assembly in accordance with aspects of this embodiment;

[0118] [Diagram 25] 1 illustrates an exploded perspective view of parts of an articulated arthroscopic cutting tool assembly in accordance with aspects of the present embodiment; FIG.

[0119] [Figure 26] 1 illustrates a perspective view of a handle of an articulated arthroscopic cutting tool assembly in accordance with aspects of this embodiment;

[0120] [Figure 27] 1 illustrates a perspective view of a linear stator shaft of an articulated arthroscopic cutting tool assembly in accordance with aspects of the present embodiment; FIG.

[0121] [Figure 28] 1 illustrates a perspective view of a distal end of an articulated arthroscopic cutting tool assembly in accordance with aspects of this embodiment;

[0122] [Figure 29] 1 illustrates a perspective view of a blade of an articulated arthroscopic cutting tool assembly in accordance with aspects of this embodiment;

[0123] [Diagram 30] 1 shows a schematic diagram of a method of preparing a surgical site using at least one of a ring curette, a square curette, or a rake curette during an arthroscopic surgical procedure according to aspects of the present embodiment.

[0124] [Diagram 31] 1 illustrates a ring curette assembly according to aspects of the present embodiment;

[0125] [Diagram 32] 13 illustrates a shaft that may be used with a ring curette assembly or a square curette assembly, according to aspects of this embodiment.

[0126] [Diagram 33] 1 illustrates a perspective view of a ring curette blade in accordance with aspects of the present embodiment;

[0127] [Diagram 34] 1 illustrates a handle assembly that may be used with a ring curette, a square curette, or a rake curette, according to aspects of the present embodiment.

[0128] [Diagram 35] 1 illustrates a square curette assembly according to aspects of the present embodiment;

[0129] [Diagram 36] 1 illustrates a square curette blade for a square curette assembly in accordance with aspects of the present embodiment;

[0130] [Figure 37] 1 illustrates a rake curette assembly according to aspects of the present embodiment;

[0131] [Figure 38] 1 illustrates a rake shaft for a rake curette assembly in accordance with aspects of the present embodiment;

[0132] [Figure 39] 1 illustrates a rake head blade for a rake curette assembly in accordance with aspects of the present embodiment;

[0133] [Diagram 40] 1 shows a schematic diagram of a method of processing a cell-seeded matrix composition for use during an arthroscopic surgical procedure according to aspects of the present embodiment.

[0134] [Figure 41A] 1 shows a diagram illustrating processing of a cell-seeding support matrix composition according to aspects of the present embodiment.

[0135] [Figure 41B] 1 shows a diagram illustrating processing of a cell-seeding support matrix composition according to aspects of the present embodiment.

[0136] [Figure 41C] 1 shows a diagram illustrating processing of a cell-seeding support matrix composition according to aspects of the present embodiment.

[0137] [Diagram 42] 1 illustrates a top perspective view of a matrix cutter according to aspects of the present embodiment;

[0138] [Diagram 43] 1 illustrates a bottom perspective view of a matrix cutter in accordance with aspects of the present embodiment; FIG.

[0139] [Diagram 44] 1 shows a schematic diagram of a method of implanting a cell-seeded matrix composition according to aspects of the present embodiment.

[0140] [Diagram 45] 13 illustrates a perspective view of a matrix shuttle delivery device with deployment wings extended, in accordance with aspects of this embodiment.

[0141] [Figure 46] 13 illustrates a perspective view of a matrix shuttle delivery device with deployment wings retracted, in accordance with aspects of this embodiment.

[0142] [Figure 47] 1 shows a side view of a delivery tip of a matrix shuttle delivery device with a cell-seeding support matrix disposed across the delivery tip, according to aspects of this embodiment.

[0143] [Figure 48] 1 shows a side view of a matrix shuttle delivery device with the deployment wings extended and the plunger depressed to deliver a cell-seeded support matrix according to aspects of the present embodiment.

[0144] [Figure 49] 1 illustrates an exploded perspective view of parts of a matrix shuttle delivery device according to aspects of this embodiment;

[0145] [Figure 50] 13 shows a perspective view of a deployment wing for use with a matrix shuttle delivery device, according to aspects of the present embodiment.

[0146] [Figure 51] 1 illustrates a perspective view of an applicator tool according to aspects of the present embodiment;

[0147] [Figure 52] 1 shows a schematic diagram of an arthroscopic surgical method for repairing a cartilage defect according to aspects of the present embodiment; DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0148] definition As used herein, the term "about" as used in relation to a value refers to a value similar to a reference value in the context. In general, a person skilled in the art who is familiar with the context will fully understand the relevant degree of difference encompassed by "about" in that context. For example, in some embodiments, the term "about" can encompass a range of values ​​that are within 25%, 20%, 19%, 18%, 17%, 16%, 15%, 14%, 13%, 12%, 11%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1% or less of the reference value.

[0149] As used herein, the term "adult" refers to a human over the age of 18. In some embodiments, a human adult has a weight within the range of about 90 pounds to about 250 pounds.

[0150] The term "associated" as used herein refers to two events or entities when the presence, level and / or form of one correlates with that of the other. For example, a particular entity (e.g., a polypeptide, a gene signature, a metabolite, a microorganism, etc.) is considered associated with a particular disease, disorder, or condition if its presence, level and / or form correlates with the occurrence and / or susceptibility of the disease, disorder, or condition (e.g., across a relevant population). In some embodiments, two or more entities are physically "associated" with each other if they directly or indirectly interact with each other, such that they are in and / or remain in close physical proximity to each other. In some embodiments, two or more entities that are physically associated with each other are covalently bound to each other, and in some embodiments, two or more entities that are physically associated with each other are not covalently bound to each other, but are non-covalently bound, for example, by hydrogen bonds, van der Waals interactions, hydrophobic interactions, magnetism, and combinations thereof.

[0151] As used herein, the term "biocompatible" refers to, for example, a substance that, when placed in contact with living tissue in vivo, does not cause significant harm to such tissue. In certain embodiments, substances are "biocompatible" if they are not toxic to cells. In certain embodiments, substances are "biocompatible" if their addition to cells in vitro does not result in substantial cell death and / or their administration in vivo does not induce significant inflammation or other such deleterious effects.

[0152] As used herein, the term "chondrocyte" or "cells of cartilage" refers to cells capable of expressing biochemical markers characteristic of chondrocytes, including, but not limited to, type II collagen, aggrecan, chondroitin sulfate, and / or keratin sulfate. In some embodiments, chondrocytes or chondrocytes express morphological markers characteristic of smooth muscle cells, including, but not limited to, a round morphology in vitro. In some embodiments, chondrocytes or chondrocytes are capable of secreting type II collagen in vitro. In some embodiments, chondrocytes or chondrocytes are capable of secreting aggrecan in vitro. In some embodiments, chondrocytes or chondrocytes are capable of producing tissue or matrix with the hemodynamic properties of cartilage in vitro.

[0153] As used herein, the term "in vitro" refers to events that occur outside of a multicellular organism, such as humans and non-human animals, or in tissue removed from a multicellular organism. In the context of cell-based systems, the term may also be used to refer to events that occur within an isolated tissue sample taken from an organism (as opposed to, for example, in a test tube system).

[0154] As used herein, the term "extracellular" refers to a molecule, substance, or process that is located or occurs outside a cell or group of cells. In the context of cell-based systems, the term can be used to refer to the natural biological materials (e.g., "extracellular matrix") found adjacent to and outside a cell or group of cells.

[0155] As used herein, the term "defect" refers to an abnormality or defect in tissue, for example, within a joint of a subject. In some embodiments, the defect is a cartilaginous defect. In some embodiments, the defect is a tissue defect in an articular joint, for example, a knee joint. In some embodiments, the defect is a cartilage defect. In some embodiments, the defect is an osteochondral defect. In some embodiments, the defect is about 0.1 to about 10 cm 2 In some embodiments, the defect may have a size ranging from 10 cm 2 It may have a size larger than

[0156] As used herein, the term "density" refers to the average number of substances, e.g., cells or other objects, per unit area of ​​volume. In some embodiments, the density is cell density, i.e., the number of cells per unit of surface area. In some embodiments, the average density is approximated by dividing the number of cells seeded by the macroscopic surface area of ​​the surface on which they grow. In some embodiments, the surface is two-dimensional. In some embodiments, the surface is three-dimensional.

[0157] As used herein, the term "in vitro" refers to events that take place in an artificial environment, e.g., in a test tube or reaction vessel, in cell culture, etc., rather than within a multicellular organism.

[0158] As used herein, the term "in vivo" refers to events that occur within multicellular organisms, such as humans and non-human animals. In the context of cell-based systems, the term may be used to refer to events that occur within living cells (as opposed to, e.g., in vitro systems).

[0159] As used herein, the term "medium" refers to components that support the growth or maintenance of cells in culture. In some embodiments, it may include conventional liquid cell culture media and additional factors. In some embodiments, the additional factors may include, for example, serum, antibiotics, growth factors, drugs, buffers, pH indicators, etc. In some embodiments, the medium may be used in the process of isolating cells (e.g., chondrocytes and / or chondrocyte precursors) from a tissue sample (e.g., a cartilage sample). In some embodiments, the tissue is mechanically disrupted (e.g., minced, chopped, blended) and then combined with the medium. In some embodiments, the medium includes enzymes (e.g., collagenase, protease) to digest the tissue and release the cells.

[0160] As used herein, the term "conditioned medium" refers to medium that has been in contact with cells, allowing the composition of the medium to be modified, for example, by the uptake or release of one or more metabolic products, nutrients, or factors.

[0161] As used herein, the term "patient" refers to any organism to which a provided composition is or may be administered, for example, for experimental, diagnostic, prophylactic, cosmetic, and / or therapeutic purposes. Typical patients include animals (e.g., mammals such as mice, rats, rabbits, non-human primates, and / or humans). In some embodiments, the patient is human. In some embodiments, the patient is suffering from or susceptible to one or more disorders or conditions. In some embodiments, the patient exhibits one or more symptoms of a disorder or condition. In some embodiments, the patient has been diagnosed with one or more disorders or conditions. In some embodiments, the patient is undergoing or has undergone a particular therapy to diagnose and / or treat a disease, disorder, or condition.

[0162] As used herein, the term "seeding" refers to a process or step by which cells contact and attach (with or without adhesive) to a support matrix (e.g., a collagen membrane) for a period of time. The seeded cells may divide and / or differentiate on the support matrix. Some cells are seeded on the support matrix prior to being implanted into a subject.

[0163] As used herein, the term "subject" refers to an organism, typically a mammal (e.g., in some embodiments, a human, including prenatal human forms). In some embodiments, the subject suffers from the relevant disease, disorder, or condition. In some embodiments, the subject is susceptible to the disease, disorder, or condition. In some embodiments, the subject exhibits one or more symptoms or characteristics of the disease, disorder, or condition. In some embodiments, the subject does not exhibit any symptoms or characteristics of the disease, disorder, or condition. In some embodiments, the subject is one who has one or more characteristics characteristic of susceptibility to or risk for a disease, disorder, or condition. In some embodiments, the subject is a patient. In some embodiments, the subject is an individual to whom and / or to whom diagnosis and / or treatment is being administered. In some embodiments, the subject is a donor of a biological sample, tissue, and / or material.

[0164] As used herein, the term "substantially" refers to a qualitative condition that indicates a degree or extent of a feature or characteristic of interest, either entirely or nearly entirely. Those skilled in the art of biology will understand that biological and chemical phenomena rarely, if ever, proceed to completion and / or completeness, or achieve or avoid absolute results. Thus, the term "substantially" is used herein to capture the potential lack of completeness inherent in many biological and chemical phenomena.

[0165] As used herein, the term "substantially free of endotoxin" refers to a level of endotoxin per dose of the composition that is less than that permitted by the FDA for biologics (i.e., total endotoxin of 5 EU / kg body weight per hour, which is 350 EU per total dose for an average 70 kg human).

[0166] As used herein, the term "substantially free of mycoplasma and / or microbial contamination" refers to a negative reading in a commonly accepted test for contamination known to one of skill in the art. For example, mycoplasma contamination is determined by subculturing a product sample in broth medium and distributing the culture on agar plates at 1, 3, 7, and 14 days at 37°C along with appropriate positive and negative controls. In some embodiments, mycoplasma contamination is determined using a real-time PCR method. The appearance of the product sample is compared to that of the positive and negative controls by microscopy at 100x. Additionally, the presence of mycoplasma contamination may be detected by inoculation of an indicator cell culture that is incubated for 3 and 5 days and then examined by epifluorescence microscopy at 600x using a DNA-binding fluorescent dye. A composition is considered satisfactory if the agar and / or broth medium procedures and the indicator cell culture procedures show no evidence of mycoplasma contamination. In some embodiments, the assay that may be utilized to assess the level of microbial contamination may be or include the United States Pharmacopeia (USP) direct introduction method. This involves inoculating samples into tubes containing tryptic soy broth medium and fluid thioglycollate medium. The tubes are observed periodically for a cloudy appearance (turbidity) during a specified period of incubation (e.g., 14 days). A cloudy appearance of either medium on any day indicates contamination, while a clear appearance (no growth) indicates that the composition may be considered substantially free of contaminants. In some embodiments, approved methods are used that are alternatives to the USP method for detection of microbial contamination, such as the BacT / ALERT test, which uses a different media formulation.

[0167] As used herein, the term "surface area" refers to, for example, the area of ​​a square, cm 2 , or the macroscopic surface area of ​​a substrate.

[0168] As used herein, the term "treatment" (also "treat" or "treating") refers to the administration of a therapy that partially or completely alleviates, improves, relieves, inhibits, delays the onset of, reduces the severity of, and / or reduces the occurrence of one or more symptoms, characteristics, and / or causes of a particular disease, disorder, and / or condition. In some embodiments, such treatment may be of subjects who do not show signs of the associated disease, disorder, and / or condition, and / or who show only early signs of the disease, disorder, and / or condition. Alternatively or additionally, such treatment may be of subjects who show one or more established signs of the associated disease, disorder, and / or condition. In some embodiments, treatment may be of subjects who have been diagnosed as suffering from the associated disease, disorder, and / or condition. In some embodiments, treatment may be of subjects known to have one or more susceptibility factors that are statistically correlated with an increased risk of developing the associated disease, disorder, and / or condition.

[0169] Injuries to joints frequently occur from physical activities, including but not limited to, for example, repetitive and excessive movement, overstretching, and physical trauma. Treatment of joint injuries often involves surgery. Tissues, including cartilage, that are internal to articular joints are often difficult to surgically access, presenting a challenge to treating patients with injuries to articular cartilage. Certain current therapeutic intervention strategies usually involve removing broken or dislodged cartilage from the joint. While such treatments usually temporarily alleviate symptoms of injury, they do not treat the origin of the lesion, or the defect, and in particular do not prevent the progressive deterioration of cartilage.

[0170] The present disclosure provides improved techniques useful for treating tissue defects in articular joints. In particular, the present disclosure provides improved matrix-induced autologous chondrocyte implantation (MACI) techniques useful for repairing tissue defects in articular joints of human subjects. For example, among other things, the present disclosure provides techniques for arthroscopic delivery of MACI implants, also known as cell-seeded support matrices. In some embodiments, the provided techniques are characterized by achieving delivery characterized by cell numbers and viability comparable to those observed with non-arthroscopic delivery. Advantages of the provided methods include arthroscopic delivery, which is much less invasive than, for example, open surgical strategies typically used to administer MACI implants. Thus, the provided techniques represent and embody further improvements to MACI techniques for the treatment of cartilage defects.

[0171] Matrix-Induced Autologous Chondrocyte Implantation (MACI) Matrix-induced autologous chondrocyte implantation (MACI) is a surgical procedure used to treat symptomatic full-thickness cartilage lesions of the articular joint. MACI® also refers to a commercial product owned by Vericel Corporation known as Autologous Cultured Chondrocytes on Porcine Collagen Membrane. MACI is a registered trademark of Vericel Corporation, but is not always indicated by the registered symbol, as it is also used herein to describe the process. MACI procedures are most commonly performed on the knee, but can also be performed on other joints. MACI improves upon the limitations of conventional methods for treating cartilage defects using implanted chondrocytes, including uneven distribution of chondrocytes upon implantation and the risk of graft hypertrophy. Given the malleability of the seeding scaffold or matrix, the graft can be easily shaped to treat irregular cartilage defects and applied to articular surfaces of multiplanar shape (e.g., trochlea) before delivery to a patient in need of chondrocytes (Jones & Cash, 2019, Arthroscopy Techniques, 8(3), 259-266).

[0172] Reparative treatment options for symptomatic full-thickness chondral and osteochondral lesions of the knee continue to evolve with advances in our understanding of cartilage biology and surgical techniques. Since its first report by Brittberg et al. in 1994, autologous chondrocyte implantation (ACI) has gained widespread application, with surgical utilization in the United States nearly doubling in the past decade. Long-term clinical results of first-generation techniques have demonstrated sustained functional improvement, but there were significant technical challenges and adverse events associated with the mandatory use of a periosteal patch over the defect. A large number of patients developed arthrofibrosis and graft hypertrophy, necessitating additional surgical procedures to address these complications (Jones, KJ & Cash, BM, Arthrosc Tech, 2019). Finally, in 2007, the use of periosteum was largely abandoned in favor of bioabsorbable collagen membrane covers, resulting in a significant decrease in graft hypertrophy and reoperation rates (Jones & Cash, 2019, Arthroscopy Techniques, 8(3), 259-266).

[0173] More recent ACI techniques, including MACI, use cell-loaded membranes to avoid implantation-related complications and simplify surgical procedures. MACI® scaffolds (Vericel Corporation, Cambridge, MA) contain 250,000–1 million cells / cm. 2 A porcine type I / III collagen membrane seeded with autologous chondrocytes at a density of 100-200 μg / cm2 can be used. A recent report on the superiority of MACI implants versus microfracture treatment trial showed that MACI® can be used to treat cartilage defects (≥ 3 cm2). 2 Clinical outcomes after treatment with TMJ were clinically superior at 5 years compared with treatment with microfractures (Brittberg et al., 2018, Am. J. Sports Med., 46, 1343-1351). Further case series have reported similar mid-term and long-term results (Jones & Cash, 2019, Arthroscopy Techniques, 8(3), 259-266).

[0174] cell In some embodiments, the present disclosure utilizes cells from human or non-human (xenograft) sources. In some embodiments, the utilized cells are human cells.

[0175] In some embodiments, the utilized cells are autologous in that they are obtained from the same subject as the subject to whom the cell-seeded matrix composition(s) as described herein will be administered. In some embodiments, the utilized cells are allogeneic in that they are isolated from the tissue of a first subject, which is a different subject than the subject to whom the cell-seeded matrix composition will be administered.

[0176] In some embodiments, the cells may be obtained from tissue harvested from a living source (e.g., a living human). In some embodiments, the cells may be obtained from tissue harvested from an adult organism (e.g., an adult). In some embodiments, the cells may be obtained from tissue harvested from a human under the age of 18. Alternatively, or in addition, in some embodiments, the cells may be obtained from tissue harvested from a deceased source (e.g., a cadaver). In some embodiments, the cells may be obtained from tissue harvested from a living non-human organism.

[0177] In some embodiments, the utilized cells comprise chondrocytes, hi some embodiments, the utilized cells comprise human chondrocytes.

[0178] In some embodiments, cell preparations utilized in accordance with the present disclosure may be characterized, for example, to confirm one or more features of cell identity and / or to exclude one or more contaminants or undesirable characteristics, etc. For example, in some embodiments, preparations that are or include chondrocytes may be assessed for expression of one or more chondrocyte markers (e.g., to determine whether expression of such markers is above a predetermined threshold and / or is comparable to expression observed in a suitable reference preparation) and / or expression of one or more fibroblast markers (e.g., to determine whether expression of such markers is below a predetermined threshold and / or is comparable to expression observed in a suitable reference preparation). In some embodiments, the chondrocyte markers may be or include HAPLN1, MGP, EDIL3, WISP3, AGC1, COMP, COL2A1, COL9A1, COL11A1, LECT1, 81008, CRTAC1, SOX9, and NEBL.

[0179] Cells for use with the techniques of the present disclosure may be obtained from biological samples such as tissues, cell cultures, or other materials that may or may not contain chondrocytes.

[0180] In some embodiments, the cell culture may be grown from cells released from a cartilage biopsy. For example, chondrocytes may be cultured from a cartilage biopsy of the patient who will receive the implant. The Carticel® autologous chondrocyte product (Vericel Corporation, Cambridge, MA) is an example of a cultured chondrocyte product. In some embodiments, the cell culture comprises a collagen matrix loaded with chondrocytes. Such chondrocytes may be taken from a cartilage biopsy and cultured before being loaded onto a matrix, for example as used in the MACI® implant product.

[0181] In some embodiments, autologous chondrocytes may be cultured and expanded prior to implantation into the subject from whom they were isolated. In step 1, a cartilage biopsy from a patient receiving autologous chondrocyte implantation may be shipped for processing (step 2). In step 3, the biopsy is digested to release the chondrocytes from the cartilage and collected. The released cells may be seeded into tissue culture flasks and expanded in primary culture in step 4, and subcultured as needed. Once the cells reach a suitable number, they may be optionally cryopreserved in step 5 until the patient is ready to receive the implant. Once the patient is ready to receive the cells, they may be thawed, plated in tissue culture flasks, and expanded to prepare an assembly culture (step 6). Once the assembly culture has a sufficient number of cells for use in an autologous chondrocyte implant, the cells may be centrifuged into a cell pellet and resuspended in transport medium, which is the "final product", e.g., the Carticel® autologous chondrocyte product (step 8). This "final product" may undergo several quality control tests, including sterility testing, cell viability testing, endotoxin testing, mycoplasma testing, and / or culture composition testing (step 9) to ensure that the cultured cells contain sufficient numbers of chondrocytes. If the cultured cells pass all tests, they may be shipped (step 10) to the patient for implantation (step 11).

[0182] Alternatively, if the assembly culture from step 6 is to be used for a MACI® implant, the cells may be resuspended in medium, seeded onto a collagen scaffold, and cultured for 4 days (step 7). At the end of the culture period, the cells may be rinsed with transport medium to produce the final product for the MACI® implant. This product may also be subjected to quality control testing. Thus, whether the final product is a suspension of cultured chondrocytes, such as Carticel® autologous chondrocytes, or the final product is a scaffold-seeded product for a MACI® implant, assessment of cell identity may be useful as a lot identification assay or lot release assay to confirm that the composition of the cell culture includes chondrocytes prior to shipping of the culture.

[0183] In some embodiments, RNA expression levels for genes overexpressed by chondrocytes (e.g., HAPLN1) can be measured in cultured cells. In some embodiments, RNA expression for genes overexpressed by synoviocytes (e.g., MFAP5) can be measured in cultured cells. In some embodiments, RNA expression levels may be presented as a ratio of expression of a chondrocyte marker (e.g., HAPLN1) to expression of a synoviocyte marker (MFAP5). In some embodiments, cultured chondrocytes may demonstrate relative RNA expression levels (HAPLN1 vs. MFAP5) of about -2, about -1, about 0, about +1, about +2, about +3, about +4, about +5, about +6, about +7, about +8, about +9, about +10 or more on a logarithmic scale. In some embodiments, cultured chondrocytes may demonstrate relative RNA expression levels ranging from about -2 to about +10, about -1 to about +9, about 1 to about 10, about +3 to about +8, about +5 to about +7, or ranges therein. In some embodiments, the cultured synovial cells may demonstrate a relative RNA expression level of less than about -2 on the log scale. In some embodiments, the cultured synovial cells may demonstrate a relative RNA expression level ranging from less than about -2 to -10 on the log scale.

[0184] In some embodiments, the chondrocytes prepared from the source cell preparation have at least 250,000 cells / cm 2 In some embodiments, chondrocytes grown in culture may be present in a sufficient density to be seeded onto a support matrix at 30° C. In some embodiments, chondrocytes grown in culture may dedifferentiate when present in monolayer culture. In some embodiments, dedifferentiated chondrocytes may exhibit a fibroblast phenotype. In some embodiments, dedifferentiated chondrocytes may downregulate expression of genes encoding extracellular matrix (ECM), e.g., ACAN and / or COL2A1. In some embodiments, dedifferentiated chondrocytes may make and / or secrete lesser amounts of ECM proteins, e.g., collagen (e.g., type II collagen) and / or aggrecan (also known as cartilage-specific proteoglycan core protein, or chondroitin sulfate proteoglycan 1). Without wishing to be bound by theory, dedifferentiation may occur following removal of chondrocytes from the three-dimensional cartilage matrix and is observed during growth of the cells in monolayer culture.

[0185] In some embodiments, the chondrocyte preparations utilized herein comprise a sufficient number of cells to seed a support matrix. In some embodiments, the chondrocyte preparation comprises at least about 3×10 cells following the second passage. 6 , 4×10 6 , 5×10 6 , 6×10 6 , 7×10 6 , 8×10 6 , 9×10 6 In some embodiments, the chondrocyte preparation comprises at least about 3×10 cells after the second passage. 6 In some embodiments, the chondrocyte preparations disclosed herein comprise at least about 1 x 10 cells at the final passage. 7 , 2×10 7 , 3×10 7 , 4×10 7 , 5×10 7 , 6×10 7 , 7×10 7 , 8×10 7, 9×10 7 In some embodiments, the chondrocyte preparations utilized herein comprise at least 1×10 cells at the final passage. 7 Contains cells.

[0186] In some embodiments, the chondrocyte cultures are about 50%, 60%, 70%, 80%, 90%, 95%, 98% or more confluent. In some embodiments, the chondrocyte cultures are about 100% confluent. In some embodiments, the chondrocyte cultures are about 50%-90% confluent.

[0187] In some embodiments, the chondrocytes are at least 250,000 cells / cm 2 , 300,000 cells / cm 2 , 400,000 cells / cm 2 , 500,000 cells / cm 2 , 600,000 cells / cm 2 , 700,000 cells / cm 2 , 800,000 cells / cm 2 , 900,000 cells / cm 2 , 1,000,000 cells / cm 2 The cells are seeded onto the support matrix at a density equal to or greater than 100 μg / ml.

[0188] In particular, the present disclosure utilizes cell preparations in which a significant proportion of the cells are viable; such high viability cell preparations can significantly improve, and may be required, successful treatment of certain lesions or defects. In some embodiments, at least 70%, 75%, 80%, 85%, 90%, 95%, 98% or more of the cells present in the preparation are viable. In some embodiments, at least 90% of the chondrocytes in the preparation are viable.

[0189] In some embodiments, the compositions of the disclosure utilized herein may be substantially free of components (e.g., bovine fetal serum albumin, bovine fetal serum, and / or horse serum) used during the preparation of source cell preparations and during the expansion of chondrocytes. For example, in some embodiments, the compositions utilized herein comprise less than 10 μg / ml, 5 μg / ml, 4 μg / ml, 3 μg / ml, 2 μg / ml, 1 μg / ml, 0.05 μg / ml of bovine fetal serum albumin. In some embodiments, the cell preparation may be substantially free of mycoplasma, endotoxin, and / or microbial (e.g., aerobic microorganism(s), anaerobic microorganism(s), and / or fungi) contamination. In some embodiments, the cell preparation may test negative for mycoplasma, endotoxin, and / or microbial contamination.

[0190] Support Matrix A support matrix for use in accordance with the present disclosure may be made from a material to which the relevant utilizing cells will adhere, hi some embodiments, the support matrix includes and / or is coated with an adhesive that promotes and / or enables cell attachment.

[0191] In some embodiments, the support matrix supports cell growth.

[0192] In some embodiments, the support matrix is ​​bioabsorbable. In some such embodiments, the bioabsorbable matrix may degrade over a period of hours, days, weeks, or months. For example, the bioabsorbable matrix may degrade within at least 24 hours, within at least 7 days, within at least 30 days, or within at least 6 months. In some embodiments, the support matrix may act as a hemostatic barrier to inhibit the infiltration of adjacent cells and tissues into certain areas of the body, such as areas requiring treatment (e.g., articular joints).

[0193] In some embodiments, the support matrix may be a gel, a solid, or a semi-solid. In some embodiments, the support matrix may be impermeable, permeable, or semi-permeable (e.g., containing holes). In some embodiments, the support matrix may be composed of synthetic materials, natural materials, or a combination thereof.

[0194] In some embodiments, the support matrix may have a structure comprising a membrane, microbeads, fleece, threads, gel, or combinations thereof.

[0195] In some embodiments, the support matrix may be or include biological material produced by cells. In some such embodiments, the biological material may be produced by cells in culture. Alternatively, in some such embodiments, the biological material may be produced by cells in a tissue (e.g., in vivo). In some embodiments, such biological material may be produced by cells that are allogeneic to the subject receiving treatment as described herein.

[0196] In some embodiments, the support matrix may be or include collagen. For example, the support matrix may be or include type I collagen, type II collagen, type III collagen, or a combination thereof (e.g., may include a combination of type I collagen and type II collagen, or may include a combination of type I collagen and type III collagen). In some embodiments, the support matrix is ​​composed primarily of type I collagen on a first side and type III collagen on a second side. In some embodiments, the first side of the support matrix that includes type I collagen is a smooth side. In some embodiments, the second side of the support matrix that includes type III collagen is a rough side. In some embodiments, the rough side of the support matrix is ​​suitable for cell seeding. In some embodiments, the smooth side of the support matrix is ​​suitable for contacting the articular surface.

[0197] In some embodiments, some or all of the collagen in a support matrix for use in accordance with the present disclosure may be crosslinked, and in some embodiments, it may not be crosslinked.

[0198] In some embodiments, collagen utilized in accordance with the present disclosure may be derived from animals such as pigs, hi some embodiments, collagen may be derived from pig peritoneum.

[0199] In some specific embodiments as described herein, the support matrix comprises a combination of types I and III porcine collagen.

[0200] In some embodiments, cells (e.g., chondrocytes) seeded and / or cultured on a support matrix as described herein may produce one or more extracellular matrix proteins (e.g., collagen) that interact with and / or become incorporated into the support matrix.

[0201] In some embodiments, the support matrix may comprise proteins, polypeptides, hyaluronic acid) and / or polymers (e.g., elastin, fibrin, laminin, fibronectin). In some embodiments, the support matrix may be cell-free.

[0202] In some embodiments, the support matrix may have an appropriate surface area, size, shape and / or dimensions for treatment of a particular cartilage or osteochondral defect, lesion or injury, hi some embodiments, the support matrix may be provided in a form (e.g., a sheet form) that is easily shaped (e.g., by cutting, trimming, etc.) for administration to a particular cartilage or osteochondral defect.

[0203] In some embodiments, the surface area of ​​the support matrix is ​​at most about 10 cm 2 , 5cm 2 , 4cm 2, 3cm 2 , 2cm 2 , 1cm 2 In some embodiments, the support matrix may be about 2 cm or less. 2 In some embodiments, the support matrix can have a surface area of ​​about 3 cm 2 In some embodiments, the support matrix can have a surface area of ​​about 4 cm 2 The dimensions of the support matrix may be any dimension necessary to achieve the desired surface area suitable for treating cartilage and / or osteochondral defects. For example, 5 cm 2 The dimensions of the support matrix may be about 1 cm x 5 cm, 2 cm x 2.5 cm, 3 cm x 1.7 cm, or 4 cm x 1.3 cm. In some embodiments, the surface area of ​​the support matrix (e.g., collagen membrane) is about 5 cm with dimensions of about 1 cm x 5 cm. 2 In some embodiments, the surface area of ​​the support matrix (e.g., collagen membrane) may be about 2×1 cm 2 With dimensions of approximately 2cm 2 In some embodiments, the maximum dimension of the support matrix does not exceed about 5 cm in its maximum length. In some embodiments, the maximum dimension of the support matrix does not exceed about 10 cm in its maximum length. In some embodiments, the support matrix has an irregular shape.

[0204] Cells seeded on a support matrix Among other things, the present disclosure utilizes a composition comprising cultured cells (eg, chondrocytes) seeded onto a support matrix (eg, a collagen membrane).

[0205] Typically, cells that have been cultured for a period of time (e.g., 3 days to 5 weeks) may reside on or in a support matrix. In some embodiments, cells seeded onto the support matrix may be adherent. In some embodiments, the cells may adhere to the support matrix to the extent that they are not washed off the matrix during subsequent cell culture steps, are not dislodged from the matrix during transportation, and / or are not dislodged from the matrix during a surgical procedure to implant the matrix.

[0206] In particular, in some embodiments, the present disclosure utilizes a cell-seeded support matrix in which a significant proportion of cells are viable; such high viability of cells present in the cell-seeded matrix can and may be required to significantly improve successful treatment of certain lesions or defects. In some embodiments, at least 70%, 75%, 80%, 85%, 90%, 95%, 98% or more of the cells present in the cell-seeded matrix are viable. In some embodiments, at least 90% of the chondrocytes present in the cell-seeded matrix are viable.

[0207] In some embodiments, the cells seeded on the cell-seeded support matrix are viable for at least about 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 7 days, 8 days, 9 days, 10 days, 11 days, 12 days, 13 days, 2 weeks, 3 weeks, or more. In some embodiments, the cells seeded on the support matrix divide. In some embodiments, the cell-seeded support matrix is ​​stored at about 4° C. to about 37° C.

[0208] In some embodiments, the cell-seeded support matrix has at least 250,000 cells / cm 2 , 300,000 cells / cm 2 , 400,000 cells / cm 2 , 500,000 cells / cm 2 , 600,000 cells / cm 2 , 700,000 cells / cm 2 , 800,000 cells / cm 2, 900,000 cells / cm 2 , 1,000,000 cells / cm 2 In some embodiments, 250,000 cells / cm or more. 2 , 300,000 cells / cm 2 , 400,000 cells / cm 2 , 500,000 cells / cm 2 , 600,000 cells / cm 2 , 700,000 cells / cm 2 , 800,000 cells / cm 2 , 900,000 cells / cm 2 , 1,000,000 cells / cm 2 The cell-seeded support matrix containing more than the cells is suitable for implantation into a subject.

[0209] In some embodiments, the cell-seeded support matrix comprises at least 5×10 6 , 7.5×10 6 , 1.0×10 7 , 1.5×10 7 , 2.0×10 7 , 2.5×10 7 , 3.0×10 7 In some embodiments, the cell culture medium comprises 20 cm 2 The membranes of porcine type I and type III collagen have a density of approximately 1.0 × 10 7 chondrocytes ~ approx. 2.0 x 10 7 In some embodiments, the chondrocytes comprise 14.5 cm 2 The membranes of porcine type I and type III collagen have a density of approximately 7.5 × 10 7 chondrocytes ~ approx. 1.5 x 10 7 The chondrocytes comprise

[0210] In some embodiments, the cell-seeded support matrix may include culture medium (e.g., DMEM) and nutritional supplements (e.g., fetal bovine serum, antibiotics). In some embodiments, the culture medium includes about 7%, about 8%, about 9%, about 10%, about 11% fetal bovine serum. In some embodiments, the culture medium may be supplemented with 8.9% + / - 0.2% fetal bovine serum and gentamicin.

[0211] In some embodiments, the cell-seeded support matrix has a surface area of ​​up to about 20 cm 2 , 10cm 2 , 5cm 2 , 4cm 2 , 3cm 2 , 2cm 2 , 1cm 2 In some embodiments, the cell-seeded support matrix may be about 2 cm or smaller. 2 In some embodiments, the cell-seeded support matrix may have a surface area of ​​about 3 cm 2 In some embodiments, the cell-seeded support matrix may have a surface area of ​​about 4 cm 2 In some embodiments, the cell-seeded support matrix may have a surface area of ​​about 5 cm 2 In some embodiments, the cell-seeded support matrix has a surface area of ​​about 10 cm. In some embodiments, the maximum dimension of the cell-seeded support matrix does not exceed about 5 cm at its maximum length. In some embodiments, the cell-seeded support matrix can be trimmed, shaped, cut, shaped, or formed to correspond to the shape of the defect, lesion, and / or injury requiring treatment. In some embodiments, the cell-seeded support matrix is ​​of an irregular shape.

[0212] In some embodiments, the cell-seeded support matrix may be substantially free of components (e.g., bovine fetal serum albumin, fetal bovine serum, and / or horse serum) used during the preparation of source cell preparations during chondrocyte proliferation. For example, in some embodiments, the cell-seeded support matrix utilized herein comprises less than 10 μg / ml, 5 μg / ml, 4 μg / ml, 3 μg / ml, 2 μg / ml, 1 μg / ml, 0.05 μg / ml of bovine fetal serum albumin. In some embodiments, the cell-seeded support matrix may be substantially free of mycoplasma, endotoxin, and / or microbial (e.g., aerobic microorganism(s), anaerobic microorganism(s), and / or fungi) contamination.

[0213] In some embodiments, the cell-seeded support matrix composition prepared and / or utilized in accordance with the present disclosure comprises a biocompatible adhesive or glue. In some embodiments, at least a portion of the cell-seeded matrix may be coated with a biocompatible adhesive or glue. In some embodiments, the biocompatible adhesive or glue may form a layer over the cells on the support matrix. In some embodiments, the biocompatible adhesive or glue may form a layer under the cells on the support matrix. In some embodiments, the cell-seeded support matrix comprises multiple layers of biocompatible adhesive or glue and cells. In some embodiments, the biocompatible adhesive or glue may be impregnated within the support matrix.

[0214] In some embodiments, the present disclosure utilizes cells and glues and / or adhesives that are combined together in a mixture of one or more alternating layers of cells and glues and / or adhesives on the surface or edge of a support matrix.

[0215] In some embodiments, biocompatible adhesives or glues used in the compositions of the present disclosure may include organic fibrin glues (e.g., TISSEEL®, a fibrin-based adhesive available from Baxter, Austria) or fibrin glues prepared during surgery using autologous blood.

[0216] Cell Sheet Among other things, the present disclosure makes use of compositions comprising cultured cells (eg, chondrocytes) formed into sheets (ie, cell sheets).

[0217] In some embodiments, the cell sheet comprises cells within their native extracellular matrix (ECM). In some embodiments, the cell sheet comprises chondrocytes within their native ECM. In some embodiments, the native ECM comprises collagen, proteoglycans, hyaluronic acid, and / or chondroitin sulfate.

[0218] In some embodiments, the cell sheet comprises a confluent cell monolayer, the confluent cells being in their native extracellular matrix.

[0219] Injury and location In some embodiments, the present disclosure contemplates the use of cells (e.g., chondrocytes) seeded and grown on a support matrix (e.g., collagen membrane) to treat / repair cartilage defects, lesions, and / or injuries in a subject. In some embodiments, the cartilage defects, lesions, and / or injuries may be located in the subject's articular joint (e.g., knee, ankle, elbow, shoulder, hip, or wrist). In some embodiments, defects in the subject's medial femoral condyle, lateral femoral condyle, patella, or trochlea may be treated using the techniques of the present disclosure.

[0220] The types of damage that may lead to cartilage defects treatable using the techniques of the present disclosure may include, but are not limited to, damage caused by chronic and / or repetitive activities, prolonged strenuous physical activities, and trauma. Some examples of chronic and / or repetitive activities include, but are not limited to, walking, running, cycling, climbing, and other movements performed during exercise. Some examples of prolonged strenuous activities include, but are not limited to, lifting heavy objects, and other forms of physical labor. Some examples of trauma include, but are not limited to, falls, collisions, and sports-related injuries.

[0221] In some embodiments, the subject to be treated may be an adult human. In some embodiments, the subject to be treated may be under 18 years of age. In some embodiments, the subject to be treated is a human between 10 and 17 years of age, and in some such embodiments, the subject does not have open growth plates. In some embodiments, the subject exhibits symptoms of cartilage defects. In some embodiments, symptoms of cartilage defects may include joint pain, joint swelling, and / or changes in joint flexibility and / or movement. In some embodiments, the subject may be asymptomatic.

[0222] method The present invention provides techniques for delivering cell-containing compositions to a surgical site, which may be useful, for example, in the treatment of cartilage and / or osteochondral lesions (e.g., localized lesions in the load-bearing areas of the articular cartilage of the knee).

[0223] In some embodiments, the present disclosure provides techniques that enable and / or achieve the treatment of clinically significant cartilage and / or osteochondral lesions, defects, injuries and / or trauma, hi some embodiments, the treatment comprises tissue repair and / or regeneration.

[0224] In some embodiments, compositions comprising chondrocytes may be implanted into a subject using arthroscopic techniques at or near the site of a lesion, defect, injury, and / or trauma, e.g., at or near an articular surface. Articular surfaces that may be treated using the methods and compositions of the present disclosure include, for example, the articular surfaces of the knee, ankle, wrist, hip, elbow, and / or shoulder. Open Dosing

[0225] Traditionally, procedures to implant cell-seeded support matrices into defect, lesion, and / or injury sites have been performed under open surgical conditions that require large incisions adjacent to the site. Implantation of cell-seeded support matrices has traditionally been performed under sterile conditions through an arthrotomy adjacent to the site. In many of these procedures, mini-arthroplasty is used. Mini-arthroplasty for repairing knee defects (e.g., condyle and patellar lesions) typically requires an incision about 6 cm to about 10 cm long. Open surgical procedures such as arthrotomy are commonly used because they allow the surgeon to not only visualize and measure the defect, but also relatively easily physically manipulate the implant near the defect.

[0226] The present disclosure recognizes various shortcomings of open surgical techniques, including those traditionally used in MACI procedures, when compared to minimally invasive techniques such as arthroscopy. For example, the relatively large incisions required to perform many open surgical techniques, including those traditionally used in MACI procedures, can result in increased risk of infection, significantly increased risk of scarring, longer recovery times, and greater pain when compared to the same indications following minimally invasive surgery, such as arthroscopic implants.

[0227] In such open surgical procedures, an incision is typically made to allow access to the joint to be surgically treated, so that the joint and its internal tissues (e.g., cartilage) are exposed and visible to the surgeon. Typically, preparation of the surgical site may include cleaning the site and removing damaged cartilage from the site. Typically, the cell-seeded support matrix is ​​positioned such that the cells face (e.g., in contact with) the surface to be treated. In some such procedures, the cell-seeded support matrix is ​​implanted into and / or over the site of the lesion, defect, and / or injury. The cell-seeded support matrix may be provided in a form that is easily molded (e.g., by folding, cutting, trimming, etc.) for administration to the cartilage or osteochondral defect (e.g., in sheet form). In some procedures, the cell-seeded support matrix is ​​molded into a form that uniquely conforms to or adheres to the cartilage or osteochondral defect of interest. The cell-seeded support matrix is ​​typically fixed into the site using a fixation method, e.g., fibrin glue fixation. The site can then be closed, leaving the cell-seeded matrix in place.

[0228] Arthroscopic Delivery Arthroscopy (also called arthroscopic surgery or keyhole surgery) is a minimally invasive surgical procedure on a joint in which an arthroscope (an endoscope inserted into the joint through a small incision) is used to examine and / or treat injuries. Arthroscopic procedures may be performed in many surgical scenarios, including, but not limited to, ACL reconstruction, meniscus reconstruction, and cartilage repair.

[0229] Arthroscopic surgery has become the preferred surgical method due at least in part to its positive impact on patient health outcomes, including but not limited to minimal soft tissue trauma, reduced postoperative pain, faster healing time, and low infection rates. Many of the surgical repairs that would benefit from MACI are performed at sites accessible using arthroscopic surgical methods. The present disclosure provides techniques that enable MACI procedures via arthroscopic delivery methods.

[0230] An important advantage of arthroscopic surgery over traditional open surgery is that it does not require opening and fully exposing the joint during the surgical procedure. In some arthroscopic procedures performed on the knee, only approximately two small incisions are made, one for the arthroscope and one for the surgical instruments used within the knee cavity. This may result in shorter recovery times and improved success rates due to less trauma to the connective tissue compared to traditional open surgery. In recent years, arthroscopy has gained popularity, at least in part due to the smaller incisions, which may result in less scarring and faster recovery times. Irrigation fluids (most commonly saline) may be used to expand the joint and create a surgical space.

[0231] In a typical arthroscopic procedure, the surgical instruments used are smaller than conventional surgical instruments. By viewing the joint area on a video monitor, the surgeon can diagnose and repair defects in the joint tissue. Arthroscopic examination of almost any joint can be performed. Arthroscopic procedures are most commonly performed on the knee, shoulder, elbow, wrist, ankle, foot, and hip.

[0232] The present disclosure identifies the causes of the challenges encountered in the delivery of cell-seeded matrix compositions via arthroscopic procedures. For example, among other things, the present disclosure identifies that in the absence of the techniques described herein, it may be difficult or impossible to maintain adequate (e.g., sufficient) levels of cell viability. Among other things, the present disclosure provides a solution. For example, the present disclosure provides techniques that have been demonstrated herein to achieve arthroscopic delivery while maintaining cell viability (e.g., as assessed by one or more parameters described herein) that is reasonably comparable to that found in certain open surgical methods. The present disclosure describes certain surprising and unexpected results (see, for example, Example 5 herein) that the provided techniques can achieve, including levels of cell viability that exceed those achieved by certain open surgical delivery methods.

[0233] In some embodiments, at least two incisions may be made adjacent to the location of the defect to be arthroscopically treated. In some embodiments, the incisions may have a length ranging from about 1 cm to about 3 cm. In some embodiments, at least one incision may be made to accommodate the insertion of an arthroscope. In some embodiments, at least one incision may be made to accommodate the insertion of a cannula. In some embodiments, at least two, at least three, or at least four incisions may be made. In some embodiments, at least two incisions may be made, each to accommodate the insertion of a cannula.

[0234] In some embodiments, the size and / or shape of the defect can be determined prior to arthroscopically implanting the cell-seeded matrix into the defect. In some embodiments, the size and / or shape of the defect can be determined by using a surgical measuring device. In the present disclosure, the surgical measuring device can be an arthroscopic probe and ruler with marks having millimeter-scale intervals.

[0235] In some embodiments, the cell-seeding support matrix can be cut using a matrix cutter to form regular shapes (eg, ovals, circles, rectangles, squares, etc.).

[0236] In some embodiments, the cell-seeded support matrix may be implanted at the site of a defect, lesion, and / or injury using arthroscopic techniques. In some embodiments, when the cell-seeded support matrix is ​​implanted at the site of a defect, lesion, and / or injury using arthroscopic techniques, the matrix may be positioned with the cells facing (e.g., in contact with) the surface to be treated. In some embodiments, the cell-seeded support matrix may be implanted arthroscopically into and / or over the site of a lesion, defect, and / or injury. In some embodiments, the cell-seeded support matrix may be provided in a form that is easily molded (e.g., by cutting, trimming, etc.) for arthroscopic administration into the cartilage or osteochondral defect (e.g., in a sheet form). In some embodiments, the cell-seeded support matrix may be molded into a form that uniquely fits or adheres to the cartilage or osteochondral defect of the subject prior to arthroscopic implantation.

[0237] In some embodiments, a region of cartilage surrounding a defect or lesion is defined by pressing a sharp cutting tool (e.g., an articulated arthroscopic cutting tool) into the cartilage, which is then removed using one or more cutting tools (e.g., ring, square, or rake curettes) to create an area of ​​exposed bone of a particular shape (e.g., oval, ellipse, circle, square, rectangle, etc.).

[0238] In some embodiments, a single matrix may be utilized to treat multiple defects by arthroscopy. In some embodiments, multiple defects may be treated, each with a different matrix, at least some of which are delivered by arthroscopy. In some embodiments, one or more defects may be treated by arthroscopy with multiple individual matrices.

[0239] In some embodiments, following treatment involving arthroscopic delivery of a composition of the present disclosure, the treated area (e.g., articular joint) may be evaluated using screening methods (e.g., magnetic resonance imaging). In some embodiments, the treated area may be evaluated for filling, repair, and / or healing of defects, lesions, and / or damage.

[0240] In some embodiments, the cell-seeded support matrix can be arthroscopically implanted at the site of the defect, lesion, and / or injury using at least one tool selected from among a cannula assembly, an arthroscopic cutting tool, a ring curette, a square curette, a rake curette, a matrix shuttle delivery device, and an applicator tool.

[0241] In some embodiments, the cannula may have an inner diameter of at least about 5 mm, at least 6 mm, at least 7 mm, at least 8 mm, at least 9 mm, or at least 10 mm. In some embodiments, the cannula may have an inner diameter of about 8 mm to about 9 mm. In some embodiments, the cannula may have an inner diameter of more than 10 mm. In some embodiments, the cannula may have an inner diameter of about 15 mm to about 20 mm. In some embodiments, the cannula may have a length of about 2 cm, about 3 cm, about 4 cm, about 5 cm, about 6 cm, about 7 cm, about 8 cm, about 9 cm, or about 10 cm or more. In some embodiments, the cannula may have a length in the range of about 2 cm to about 10 cm. In some embodiments, the cannula has a length of about 4.5 cm. In some embodiments, the length of the cannula may depend on the location of the site of the defect to be treated. For example, a cannula used to treat a hip joint defect may have a length of about 12 cm to about 20 cm. In some embodiments, a cannula used to treat a hip defect may have a length of about 16.5 cm. In some embodiments, a cannula used to treat a shoulder defect may have a length of about 12 cm to about 20 cm. In some embodiments, a cannula used to treat a shoulder defect may have a length of about 16.5 cm. As an additional example, a cannula used to treat a knee defect may have a length in the range of about 2 cm to about 7 cm. In some embodiments, a cannula used to treat a knee defect may have a length of about 4.5 cm. In some embodiments, the cannula may be comprised of a material including plastic. In some embodiments, the cannula may be comprised of a material including metal. In some embodiments, the cannula may be comprised of a material selected from the group consisting of plastic, metal, rubber, silicone, fiberglass, and combinations thereof (e.g., composite materials).

[0242] In some embodiments, one end of the cannula may be truncated into a curved shape around the circumference of the cannula to form a curved evaluation edge that may facilitate visual inspection of the curved condyle or other surface on the bone.

[0243] In some embodiments, the cell-seeded support matrix can be delivered arthroscopically to a surgical site by using tweezers or other tools to place a pre-cut or shaped portion of the cell-seeded support matrix onto a matrix shuttle device, pushing the shuttle device into a cannula placed at the surgical site, and pushing the plunger of the matrix shuttle device to push out deployment wings that can deliver the cell-seeded support matrix to the surgical site. In some embodiments, the cell-seeded support matrix can traverse the entire length of the cannula.

[0244] In some embodiments, the cell-seeded support matrix can be implanted into the defect, lesion, and / or injury, followed by a cover patch secured thereto, for example, using a biocompatible adhesive, sealant, or suture. In some embodiments, the cover patch can serve to cover the area to prevent infiltration of undesired cells and / or biological factors (e.g., fibroblasts, macrophages) from surrounding tissue into the treated area. In some embodiments, the cover patch can include any of the support matrices described herein, and / or can include hyaluronic acid, fibrin, and / or polylactic acid. In some embodiments, the cover patch can be acellular and absorbable. In some embodiments, the cover patch can be semi-permeable.

[0245] In some embodiments, the biocompatible adhesive or glue used to secure the cover patch may include organic fibrin glues or sealants (e.g., TISSEEL®, a fibrin-based adhesive available from Baxter, Austria) or fibrin glue prepared during surgery using autologous blood.

[0246] In some embodiments, a biocompatible adhesive or glue may be applied to the defect prior to placing the cell-seeded support matrix over or into the defect. In some embodiments, a biocompatible adhesive or glue may be applied to the cell-seeded support matrix prior to placing it over or into the defect. In some embodiments, a biocompatible adhesive or glue may be applied around the periphery of the implanted cell-seeded support matrix.

[0247] 1 shows a schematic diagram of a method 10 of performing arthroscopic surgery in accordance with aspects of the present embodiment. Method 10 generally includes making an incision in an affected joint of a patient (e.g., knee, shoulder, elbow, etc.) (step 12), cannulating the incision (step 14), measuring a cartilage defect in the joint using an arthroscopic measurement probe (step 16), contouring and scoring the cartilage surrounding the defect into a particular shape (e.g., oval, circle, square, rectangle, oval, etc.) using an articulated arthroscopic cutting tool (step 18), cutting, removing, and debride the cartilage within the contoured shape using a cutting tool (e.g., rake curette, ring curette, square curette, etc.) (step 20), and removing the cartilage using an applicator tool (step 21). The method may include drying the surgical site from which the cartilage has been removed by stopping fluid flow through suction, suction, and drying (step 22), applying fibrin glue to the surgical site (step 23), cutting a portion of the cell-seeded support matrix (or MACI graft or MACI implant) using a matrix cutter (step 24), delivering and implanting the cell-seeded support matrix into the prepared surgical site using a matrix shuttle delivery device (step 26), and applying fibrin glue (or other suitable material) to the defect site using an applicator tool (step 28).

[0248] FIG. 2 illustrates an exemplary arthroscopic surgical process diagram according to aspects of the present embodiment. FIG. 2A corresponds to step 16 of method 10 and illustrates a cartilage-covered joint 42. In some embodiments, the joint may be the medial femoral condyle, lateral femoral condyle, patella, or trochlea, or other joint of the subject or patient. FIG. 2A also illustrates a flexible ruler 44 deployed from a measurement tool. FIG. 2B corresponds to step 18 of method 10 and illustrates a sharp blade 46 attached to an articulated arm 48 cutting the cartilage 42. FIG. 2C corresponds to step 20 of method 10 and illustrates a ring curette 50 removing a portion of the cartilage 42. FIG. 2D corresponds to step 22 of method 10 and illustrates a matrix applicator 56 desiccates the exposed bone 54 at the joint, defining the contour 52 by cutting away the cartilage 42. Figure 2E corresponds to step 26 of method 10 and shows a shuttle device 58 delivering a portion of a pre-cut cell-seeded support matrix 60 that conforms to the shape of the treated area 52 in cartilage 42. Figure 2F corresponds to step 28 of method 10 and shows an applicator tool 62 positioning the cell-seeded support matrix 60 and applying fibrin glue within the cut area 52 of cartilage 42.

[0249] Systems / Tools / Devices Provided herein are systems, tools, devices, and instrumentation systems useful for carrying out the methods of the invention, which allow for convenient performance of the methods of the invention in a surgical environment.

[0250] In some embodiments, at least one custom device or tool can be used to perform the methods described herein.

[0251] FIG. 3 shows a schematic diagram of a method 70 of using a cannula assembly during arthroscopic surgery according to aspects of the present embodiment. Method 70 may generally include inserting a cannula assembly (step 72), where the cannula assembly may include an obturator and a dam seal subassembly, into an incision in a patient's joint. Once the cannula assembly is inserted, method 70 may include pushing and twisting the cannula body clockwise to secure it at the incision site (step 74), withdrawing the obturator from the cannula assembly (step 76), and performing one or more arthroscopic surgical procedures leaving the cannula body and dam seal subassembly behind (step 78). If desired, the dam seal subassembly may be removed from the cannula body by pushing a tab on the side of the dam seal body to release the dam body (step 80). Once the arthroscopic surgery is completed, the cannula body may be removed from the incision site by twisting it counterclockwise (step 82).

[0252] FIG. 4 illustrates a perspective view of a cannula assembly 90 according to aspects of the present embodiment. Generally, the cannula assembly 90 may include an obturator 92, a dam seal subassembly 94, and a cannula body 96. The dam seal subassembly may be coupled by a dam release clip 114 (shown in FIG. 5) that may be releasably attached to a tab 128 on the cannula body 96 such that the dam seal subassembly 94 and the body 96 are coupled to one another. The obturator 92 may be coaxially inserted through both the cannula body 96 and the dam seal subassembly 94. Generally, in some embodiments, the obturator may function as a handle used to push and twist the cannula assembly into the incision site. A plurality of slats 102 on a proximal handle portion 100 of the obturator may aid in manually holding and manipulating the obturator during insertion of the cannula assembly and may improve certain aspects of the manufacture of the obturator.

[0253] 5 illustrates how the obturator 92 and dam subassembly 94 are assembled according to aspects of the present embodiment. In general, the obturator may include two or more protruding rotation tabs 110 on the bottom surface of the proximal handle portion 100 that fit into two or more corresponding recesses 112 on the top of the dam seal subassembly 94. During insertion of the cannula assembly, the rotation tabs 110 and recesses 112 may assist in compound movement of the cannula assembly to enhance the rotational movement of the cannula assembly while not restricting the axial movement of the obturator 92. In general, the obturator includes a proximal handle portion 100 shaped like a dome to fit the operator's hand, a distal conical tip 106 that helps to wed the cannula assembly into the surgical incision, and a shaft portion 104 that connects the handle portion 100 and the pointed portion 106. In some embodiments, a plurality of slats 102 on the obturator's proximal handle portion 100 may aid in manually holding and manipulating the obturator during insertion of the cannula assembly and may improve certain aspects of the manufacture of the obturator. One or more recessed portions 180 may be present on the handle portion 100 and may enhance manually holding and manipulating the obturator during the performance of certain methods. Certain aspects of the obturator 92 are also shown in FIG. 13 and described below.

[0254] 6 and 8 show two different perspective views of the cannula body 96 according to aspects of this embodiment, and FIG. 7 shows a side view. The cannula body 96 may generally include a hollow cylinder 120 wound with a helical thread 126 along the entire length of the hollow cylinder 120. In some embodiments of the present disclosure and the present arthroscopic surgical methods, the threads around the cannula body may help to grip the incision site and allow the surgeon to expand the interior volume at the surgical site. The cannula body 120 may also include a circular lip portion 122 near the proximal end of the hollow cylinder 120, on which two tabs 128 are disposed opposite one another. In some embodiments of the present disclosure, these tabs may be releasably interfaced with two corresponding dam release clips 114 on the dam seal subassembly, so that the dam seal subassembly may be removed from or attached to the cannula body.

[0255] 6 and 7, the distal end of the hollow cylinder 120 may terminate in a circumferential edge 130 that is curved relative to a plane perpendicular to the central axis of the hollow cylinder 120. This curved circumferential edge 130 may be further outlined with a dark line to serve as a visual guide for assessing the curvature of the surgical site. Depending on the diameter of the hollow cylinder 120, the degree of curvature of the curved circumference may vary. Additionally, at least two additional visual marks 132 along the circumferential dark line may be applied at opposing locations to assist as visual markers. In some embodiments, the visual mark 132 may extend proximally from the curved periphery 130 at the distal end of the hollow cylinder 120 by about 0.1 mm to about 10 mm, or about 0.1 mm to about 0.5 mm, or about 0.1 mm to about 1.0 mm, or about 0.1 mm to about 0.8 mm, or about 0.1 mm to about 0.5 mm, or about 0.2 mm to about 1.0 mm, or about 0.2 mm to about 0.8 mm, and / or about 0.2 mm to about 0.5 mm.

[0256] In some embodiments, the cannula body 96 may include a translucent polycarbonate material. The translucent material may improve optical visibility of the surgical site through the cannula body 96 during a surgical procedure. In some embodiments, the cannula body 96 may include or be constructed from a plastic, a polymer, a metal, or a composite or hybrid material.

[0257] FIG. 9 illustrates a perspective view of a dam seal subassembly according to aspects of the present embodiment. In general, the dam seal subassembly may include one or more dam seals 154, 156, 158 (shown in FIGS. 10-12) enclosed within one or more outer pieces 148, 150, which may serve to form a flexible interface for various arthroscopic surgical tools to enter the cannula and interact at the surgical site, and may serve to retain liquids, fluids, tissue, or other materials. The outer pieces 148, 150 may include a dam top piece 148 and a dam bottom piece 150, which are shown in more detail in FIG. 10 and described below. The dam top piece 148 may include a flat upper surface 146 and a circular hole 144, and a recess 112 located at opposing locations (e.g., approximately 180 degrees apart) around the periphery of the circular hole 144. The recess 112 may mate with a rotation tab 110 on the obturator 92 (shown in FIG. 5 above).

[0258] FIG. 10 illustrates an exploded perspective view of the components of the dam seal subassembly 94, according to aspects of this embodiment. The dam seal subassembly 94 may generally include a dam top piece 148, at least one dam seal piece 158, 154, 156, and a dam bottom piece 150. In some embodiments, all of the components shown in FIG. 10 may be coaxially mated with one another or longitudinally or axially aligned and stacked parallel to one another. Generally, the dam top piece 148 and the dam bottom piece 150 may surround the dam seal pieces 158, 154, 156 to form a flexible dam seal assembly that may be cannulated with various arthroscopic surgical tools to perform surgical procedures while maintaining fluids (such as sterile saline, sterile fluids, and other materials) within the surgical site.

[0259] In some embodiments, the dam top piece 148 and the dam bottom piece 150 may comprise acrylonitrile butadiene styrene (ABS) or other similar polymeric or plastic materials.

[0260] 10, the upper dam seal piece 148 includes a flat circular portion 151 with a circular hole at its center 154. The upper dam seal piece 148 may further include a plurality of legs 152 projecting vertically downward from a bottom surface of the upper dam seal piece 148. The legs 152 include tapered cylindrical rods. In some embodiments, the legs 152 are evenly distributed around the circumference of the upper dam seal piece 148 (e.g., six legs spaced at approximately 60 degree intervals, or four legs spaced at approximately 90 degree intervals). The upper dam seal piece may further include two or more recesses 112 spaced at opposite positions (e.g., 180 degree intervals) at the edge of the circular center hole 154, which may mate with corresponding rotation tabs 110 in the obturator 92.

[0261] FIG. 11 shows a perspective view of a dam seal having slits 156, 158 and FIG. 12 shows a perspective view of a dam seal having holes 154 according to aspects of this embodiment. Typically, one or more dam seals are stacked coaxially to form a flexible dam seal. In some embodiments, the dam seals comprise silicone or ethylene propylene diene monomer rubber (EPDM rubber), or other flexible polymeric materials. Both the slit dam seals 156, 158 and the hole dam seal 154 may also include a number of small circular holes 170, 174 located near the circumference of the disk corresponding to the legs 152 of the upper dam seal piece 148. In some embodiments, the legs 152 may pass through the holes 170, 174 when the dam seal pieces are stacked coaxially.

[0262] With reference to Figure 11, the dam seal with slits 156, 158 shown in Figure 11 may include a circular disk and may feature three or more slits cut into the disk from the center toward the outer edge and angled evenly from one another. In some embodiments, there may be three slits 172 separated by approximately 120 degrees. With reference to Figure 12, the perforated dam seal 154 shown in Figure 12 may include a circular disk and may feature a small circular hole in the center of the disk.

[0263] 9-12, each of the dam seal segments 154, 156, 158 may have one or more slits 172 or zero to one central hole 176 therethrough to allow the obturator 92 to be pushed through the center of each dam seal segment 154, 156, 158. The slits 172 bend downward (i.e., distally) as the obturator 92 is pushed through. When the obturator is removed from the dam assembly 94, each of the slits 172 return to their original position (i.e., flush with the remainder of the respective dam seal segment 154, 156, 158). 10, two of the three dam seal pieces 156, 158 each have three slits 172 spaced approximately 120 degrees apart with the slits 172 in one dam seal piece 156 rotated approximately 60 degrees from the slits 172 in the other dam seal piece 158 to minimize leakage through the dam assembly when the obturator 92 is withdrawn. The third dam seal piece 154 may have a hole 176 therethrough to keep the obturator 92 centered within the dam assembly 94. Each of the dam seal pieces 154, 156, 158 may be constructed from a polymeric material that is sufficiently flexible and resilient and also includes some shape memory.

[0264] Figure 13 shows a perspective view of an obturator and Figure 14 shows a side view of the obturator, according to aspects of this embodiment. Generally, the obturator includes a proximal handle portion 100 shaped like a dome to fit an operator's hand, a distal conical tip 106 that aids in pushing the cannula assembly into a surgical incision, and a shaft portion 104 that connects the handle portion 100 and the pointed portion 106. In some embodiments, a plurality of slats 102 on the obturator's proximal handle portion 100 can aid in manually holding and manipulating the obturator during insertion of the cannula assembly and can improve certain aspects of the manufacture of the obturator. For example, each of the slats 102, and the vertical members that fill the gaps between the slats 102, can have a consistent thickness and be manufactured by a molding process (i.e., an injection molding process using coring), and the heating and cooling processes during manufacture provide consistent thermal and / or heat treatment characteristics throughout the obturator 92 (thereby reducing variability in the material properties of the resulting part).

[0265] 15 shows a view of an obturator 100 and dam seal subassembly 94 positioned near a cannula body 96 that is inserted into an incision at the joint, according to aspects of the present embodiment. The obturator 100 is inserted through the dam seal subassembly 94, allowing them to be manipulated together as a combined object. The conical distal end 106 of the obturator faces toward the opening of the cannula body 96. A dam release clip 164 may be used to releasably engage with a corresponding tab on the cannula body 96. The cannula body 96 is shown in FIG. 15 and is made from a clear polymeric material to facilitate improved visibility within the surgical site.

[0266] In some embodiments, an adjustable arthroscopic measurement device or probe is used to assess the size and shape of at least one lesion or defect in cartilage at the surgical site.

[0267] FIG. 16 illustrates a schematic diagram of a method 200 of using an arthroscopic measurement probe 210, according to aspects of the present embodiment. The method 200 may generally include inserting the measurement probe 210 into the dam seal subassembly 94 and the cannula body 96 (step 202). A flexible ruler 218 may be extended from the measurement probe near the lesion or defect (step 204). The size and shape of the lesion or defect may be measured by visual comparison with regular markings on the ruler 218 (step 206). The adjustable nature of the measurement probe 210 allows the ruler 218 to be rotated and extended or retracted to better align the ruler 218 with various features of the lesion or defect. Once measurements are completed, the ruler 218 may be retracted into the measurement probe 210, removed from the surgical site, and withdrawn from the dam seal subassembly and cannula body (step 208).

[0268] 17 and 18 show perspective views of an arthroscopic measurement probe assembly 210 according to aspects of the present embodiment. In general, the measurement probe 210 may include a handle 212, an adjustment knob 214, a rotating plug 222, a dowel pin 224, a stroke arm 226, a sizer tube 216, and a flexible ruler 218. In some embodiments, the rotating plug 222, the adjustment knob 214, the stroke arm 226, the sizer tube 216, and the flexible ruler 218 are all coaxially connected, and the adjustment knob 214 can be used to extend and rotate the ruler 218, and the flexible ruler 218 can be disposed through the interior of the sizer tube 216. In some embodiments, the distal end 220 of the sizer 216 may be bent such that there may be an angled bend of 90 degrees, or 85-95 degrees, or 75-105 degrees. In some embodiments, the radius of curvature of the bend at the distal end 220 of the sizer tube 216 can have a radius of curvature of about 0.11 inches, or about 0.05 to 0.2 inches.

[0269] 18 shows an exploded perspective view of the parts of an arthroscopic measurement probe assembly according to aspects of the present embodiment. In general, the handle 212 may include two pieces, a top shell piece 211 and a bottom shell piece 213. The adjustment knob 214 may be connected to the stroke arm 226 by a dowel pin 224 that may pass through a slit 236 located in the sizer tube 216. A dowel pin 222 may also be connected to the proximal end of the stroke arm 226 and the adjustment knob 214. In some embodiments, the arrangement and connection of these components may allow the adjustment knob 214 to be pushed along the longitudinal axis of the measurement probe device 210 to extend and retract the flexible ruler 218, and to rotate the adjustment knob 214 to rotate the sizer tube 216. The overall effect of these combined movements is that the flexible ruler 218 may be deployed at various angles and positions within the surgical site to facilitate measurement of a lesion or defect.

[0270] In some embodiments, the upper shell piece 211 and the lower shell piece 213 of the handle 212 comprise acrylonitrile butadiene styrene (ABS) or other similar plastic or polymer material and are held together by crush pins (e.g., matching offset features such as cylindrical protrusions on the upper shell piece 211 interface with corresponding octagonal sleeves on the lower shell piece 213, or vice versa), thereby holding the two pieces 211, 213 together by friction.

[0271] FIG. 19 illustrates a ruler 218 for an arthroscopic measurement probe 210 according to aspects of the present embodiment. In general, the flexible ruler 218 includes a cylindrical rod 230 including a flexible material that can bend and retain its shape. In some embodiments, the cylindrical rod 230 can include or be made of one of polyetheretherketone (PEEK), metal wire, or a polymeric material, or a combination of polymeric and metallic materials. The material(s) making up the cylindrical rod 230 can enable the flexible ruler 218 to bend through the bend opening 220 of the sizer tube 216 and maintain a substantially straight portion when unwound to facilitate measurement. The flexible ruler 218 may also be provided with a plurality of marks 232 distributed along the length of the outer surface near the distal end of the cylindrical rod 230. The marks 232 can include thin lines perpendicular to the longitudinal axis of the cylindrical rod 230 and be spaced at intervals of 2.5 mm and 5.0 mm. In some embodiments, the marks 232 may be imprinted on the ruler 218 by one or more methods including laser etching, physical etching, screen printing, and / or ink marking.

[0272] FIG. 20 illustrates a sizer tube 216 for an arthroscopic measurement probe 210, according to aspects of the present embodiment. In general, the sizer tube 216 includes a hollow cylindrical tube 234 having two slits 236 located at opposing positions at its proximal end. The sizer tube 216 may also include a bend 238 at the distal end of the tube such that the opening of the tube 240 is angled away from the longitudinal axis of the tube (allowing for measurement of surfaces approximately perpendicular to the axial or longitudinal direction). In some embodiments, the angle may be about 90 degrees. In some embodiments, the angle may be between about 75 degrees and about 105 degrees. In some embodiments, the radius of curvature of the bend 238 may be about 0.11 inches. In some embodiments, the radius of curvature of the bend 238 may be between about 0.05 inches and about 0.25 inches. In some embodiments, the sizer tube 216 may include at least one of stainless steel T304, stainless steel T316, or fractionated hypodermic tubing.

[0273] 21 illustrates a perspective view of an arthroscopic probe 210 assembly with arrows indicating movement and showing the ruler 218 in a deployed state, according to aspects of the present embodiment. The handle 212, adjustment knob 214, sizer tube 216, and flexible ruler 218 are shown and are as described above. Here, the adjustment knob 214 is shown in its most extended position, closer to the distal end of the handle. Correspondingly, the ruler 218 is shown fully deployed from the sizer tube. The straight double arrow indicates the ability of the ruler 218 to extend and retract. The curved arrow indicates the ability of the sizer 216 tube to rotate along its longitudinal axis such that the deployed ruler 218 points along different directions.

[0274] In the present disclosure, a number of cutting tools are described. Each of the tools may have one or more surgically sharp cutting edges that may be machined or manufactured to have a sufficiently sharp breaking edge to facilitate sharp cuts in biological materials that may include skin, cartilage, and / or bone. For example, in some embodiments, the cutting edges may include breaking edges of 0.002 inches, 0.001 inches, or less than 0.001 inches, as well as various subranges therebetween.

[0275] FIG. 22 illustrates a schematic diagram of a method 250 of using an articulated arthroscopic cutting tool 270 during an arthroscopic surgical procedure, in accordance with aspects of the present embodiment. Generally, the method 250 includes selecting a size of an articulated arthroscopic cutting tool 270 based on measurements obtained using the method 200 described above to measure the dimensions of the cartilage defect or lesion (step 252); removing the dam seal subassembly from the cannula, stopping fluid flow, and drying the defect site (step 253); inserting the articulated arthroscopic cutting tool 270 into the cannula 96 and dam seal subassembly 94 at the surgical site (step 254); using a thumb slider 274 on the handle 286 of the articulated arthroscopic cutting tool 270 to tilt a blade 278 on the cutting tool to the appropriate angle and lock the angle in place; pushing the blade 278 into the cartilage 42 at the surgical site surrounding the defect or lesion (step 258); and removing the articulated arthroscopic cutting tool 270 from the cannula 96 and dam seal subassembly 94 (step 260). Once inserted into the cannula, the articulated arthroscopic cutting tool 270 may be rotated from 0 degrees to 360 degrees (and subranges therebetween) within the cannula 96 (e.g., shaft 276 is disposed concentrically within the cannula). In some embodiments, after method 250 is completed, there may remain at least one oval contour 52 (shown in FIG. 2D ) defined in the cartilage that corresponds to the shape of the blade 278. A further method that may be performed after method 250 is described by method 330 and illustrated by FIG.

[0276] 23 illustrates a perspective view of an articulated arthroscopic cutting tool assembly 270 according to aspects of the present embodiment. In general, the articulated arthroscopic cutting tool assembly 270 includes a handle 272, a thumb slider 274, a linear stator shaft 276, a curved elliptical blade 278 connected to the linear stator shaft 276 by a hinged joint 280, a linear transmission shaft 292 connected to the thumb slider 274, and a link piece 282 connected to both the linear transmission shaft 292 and the curved elliptical blade 278. In some embodiments, the link piece 282 is connected to the curved elliptical blade 278 at a joint 284. In some embodiments, as the thumb slider 274 moves along the longitudinal axis of the handle, the curved elliptical blade 278 tilts about a joint 280 relative to the linear stator shaft and relative to the longitudinal axis of the articulated arthroscopic cutting tool 270. In some embodiments, the curvature of the elliptical blade 278 may enable the elliptical blade 278 to follow the curved surface of a joint, such as the medial femoral condyle, lateral femoral condyle, patella, or trochlea, of a subject or patient.

[0277] 24 illustrates a perspective view of a distal end of an articulated arthroscopic cutting tool assembly 270 in accordance with aspects of the present embodiment. Generally, the link piece 282 is connected to both the linear transmission shaft 292 and the curved elliptical blade 278 such that movement of the thumb slider 274 tilts the curved elliptical blade 278 about an axis at the joint 280, changing the angle of the curved elliptical blade 278 relative to the longitudinal axis of the articulated arthroscopic cutting tool assembly 270.

[0278] FIG. 25 shows an exploded perspective view of the parts of the articulated arthroscopic cutting tool assembly 270 according to aspects of the present embodiment. Generally, the handle includes an upper shell 286 and a lower shell 288 that combine to form the handle. In some embodiments, the upper shell 286 comprises a semi-cylinder with a protrusion and a rectangular opening 290 extending longitudinally along the semi-cylinder with the protrusion, and the lower shell 288 comprises a semi-cylinder with a protrusion. In some embodiments, when the two shells 286, 288 are closed together to form a complete cylinder, there may be a small circular opening 298 at the distal end of the handle. In some embodiments, the handle protrusions of the upper shell 286 and lower shell 288 run longitudinally along the length of the shells to provide an improved grip by a user or operator on the articulated arthroscopic cutting tool 270.

[0279] 25, the articulated arthroscopic cutting tool assembly may also include a thumb slider including a slide button 274, a slider clamp piece 296, and a spring 294 disposed vertically between the slide button 274 and the slider clamp piece 296. The slide button 274 may include a raised upper surface as the distal end of the button and a protruding upper surface at the proximal end of the button. The inner surface (i.e., underside) of the top shell 286 may be provided with a number of notches (not visible in FIG. 25) on either side of the rectangular opening 290 that may cooperate with a cylindrical pin 275 proximate the slider button 274 to lock the slider button 274 at various positions along the rectangular opening 290 (i.e., pressing down on the slider button 274 (which compresses the spring 294), sliding the slider button 274 to a desired position, and releasing the slider button 274 to engage the pin 275 with the notches in the top shell 286). This position locking mechanism may allow the curved oval blade 278 to be locked at different oblique angles relative to the longitudinal axis of the articulated arthroscopic cutting tool 270.

[0280] 26 illustrates a perspective view of a handle 272 of an articulated arthroscopic cutting tool assembly in accordance with aspects of this embodiment. Generally, the thumb button 274 protrudes slightly from a rectangular opening 290 in the handle top shell 286. A circular hole 298 formed by the top shell piece 286 and the bottom shell piece 288 of the handle 272 may allow for installation of a linear stator shaft 276 in the handle 272.

[0281] 27 illustrates a perspective view of a linear stator shaft 276 of an articulated arthroscopic cutting tool assembly according to aspects of the present embodiment. Generally, the linear stator shaft 276 comprises a cylindrical rod 300, a rectangular groove 302 cut longitudinally along the cylindrical rod 300, a reduced diameter portion 304 along the cylindrical rod 300 near its proximal end, and a circular ring 306 projecting perpendicularly from the distal end of the cylindrical rod 300. In some embodiments, the reduced diameter portion 304 can facilitate clamping with a handle 272 (which can include a corresponding internal notch for interfacing with the reduced diameter 304, thereby preventing distal, proximal, or circumferential movement of the linear stator shaft 276 relative to the handle 272). In some embodiments, the circular ring 306 can form part of a hinge or attachment for a curved elliptical blade 278.

[0282] 28 illustrates a perspective view of a distal end of an articulated arthroscopic cutting tool assembly 270 according to aspects of the present embodiment. In general, the linear stator shaft 276 may be connected to the curved elliptical blade 278 at a hinge formed by a circular ring 306 of the linear stator shaft 276 attached to two circular rings 320 extending from the curved elliptical blade 278.

[0283] 29 illustrates a perspective view of a curved elliptical blade 278 of an articulated arthroscopic cutting tool assembly according to aspects of the present embodiment. In general, the curved elliptical blade 278 may include an elliptical ring 310 and at least three crossbar pieces 312, 314, 316 spanning across the top surface of the elliptical ring 310. In some embodiments, a circular ring 318 may extend perpendicularly from the first crossbar piece 312, while two circular rings 320 may extend perpendicularly from the second crossbar piece 314. The top edge of the ring 310 may be curved, while the bottom edge of the ring may include a curved cutting surface including a surgically sharp edge 322. In some embodiments, the elliptical ring 310 may be thicker at the narrow end of the elliptical ring.

[0284] In some embodiments, the surgeon or user may have access to additional sterile components suitable for easy use in a surgical environment, which may include a suitable hemostatic barrier, a suitable cover patch, and / or an organic adhesive.

[0285] In some embodiments, the surgeon or user may have access to an acellular matrix material suitable for supporting autologous or allogeneic chondrocytes, for example suitable for implantation into a defect in an articular surface.

[0286] In some embodiments, the surgeon or user may utilize a suitable hemostatic barrier, which may be or include, for example, a Surgicel® hemostatic barrier.

[0287] In some embodiments, the surgeon or user may utilize a suitable cover patch, which may be or include a Bio-Gide® cover patch.

[0288] In some embodiments, the hemostatic barrier (e.g., Surgicel® hemostatic barrier) and / or cover patch (e.g., ACI-Maix® cover patch) may include an adhesive, e.g., a tissue adhesive, and in some embodiments, the adhesive may be an organic adhesive (e.g., Tisseel® organic adhesive). In some embodiments, the adhesive may be applied (e.g., as a cover) to allow for increased time to absorption.

[0289] In some embodiments, hemostatic barriers (e.g., Surgicel® hemostatic barrier) and / or cover patches (e.g., Bio-Gide® cover patches), particularly those treated with adhesives (which may include, for example, Tisseel®), may be supplemented with aprotinin (e.g., in a manner and / or to an extent that time to absorption is increased).

[0290] In some embodiments, both the hemostatic barrier and the cover patch may be semi-permeable collagen matrices that are treated to extend the time for absorption of the material.

[0291] In some embodiments, the instrument system may include a surgical instrument or a plurality of surgical instruments. In some embodiments, the instrument system may include one or more cannulas (e.g., 1, 2, 3, 4, 5, or 10 or more cannulas). In some embodiments, the instrument system may include a cannula or a plurality of cannulas having an inner diameter within a range of about 5 mm to about 20 mm, about 6 mm to about 12 mm, about 7 mm to about 11 mm, about 8 mm to about 9 mm, or about 10 mm to about 25 mm. In some embodiments, the cannula may be constructed of a material selected from the group consisting of plastic, metal, rubber, silicone, fiberglass, and combinations thereof (e.g., composite materials).

[0292] 30 illustrates a schematic diagram of a method 330 of preparing a surgical site using at least one of a ring curette 350, a square curette 400, or a rake curette 430 (e.g., a 3.6 mm rake curette 430) during an arthroscopic surgical procedure according to aspects of the present embodiment. Generally, method 330 is continued after method 250 is completed. Generally, the steps may include placing the dam seal subassembly 94 onto the cannula 96 and resuming fluid flow (step 331); inserting a cutting tool, which may include a ring curette 350, square curette 400, or rake curette 430, into the cannula 96 and the dam seal subassembly 94 (step 332); using the cutting tool to scrape, cut, debride, and / or remove the cartilage 42 within the elliptical area 52 previously defined by the curved elliptical blade 278 on the articulated arthroscopic cutting tool 270 (step 336); removing the cutting tool from the cannula and dam seal subassembly 94 (step 336); and, if necessary, repeating steps 332-336 until the cartilage in the cut area of ​​the cartilage has been completely removed (step 338).

[0293] 31 illustrates a ring curette assembly 350 according to aspects of the present embodiment. Generally, the ring curette assembly 350 includes a handle 352, a shaft 354 coupled to a distal end of the handle 352, and a ring curette blade 356 coupled to a distal end of the shaft 354. In some embodiments, the shaft 354 may include a cylindrical rod having at least two bends 362, 364 such that the distal end of the shaft is parallel to and offset from the main longitudinal axis of the shaft. In some embodiments, the ring curette blade 356 may include at least one surgically sharp edge 374.

[0294] 32 illustrates a shaft 354 that may be used in the ring curette assembly 350 or square curette assembly 400 according to aspects of the present embodiment. In general, the shaft 354 includes a cylindrical rod 358, a flat portion 360 at the proximal end of the cylindrical rod 358 that can be used to facilitate installation within the handle 352, a first bend 362 of the cylindrical rod 358 near the distal end of the rod such that the rod axis is angled away from the main longitudinal axis of the cylindrical rod, a second bend 364 of the cylindrical rod near the further distal end of the rod such that the rod axis is angled parallel to and eccentrically disposed from the main longitudinal axis of the cylindrical rod, a cylindrical portion 366 of reduced diameter near the distal end of the rod, and a recessed opening 368 at the distal end of the shaft having a flat inner surface.

[0295] 33 shows a perspective view of a ring curette blade 356 according to aspects of the present embodiment. In general, the ring curette blade 356 may include a hollow frustoconical ring 372, a rounded edge 370 around the larger periphery of the ring 372, a surgically sharp edge 374 around the larger periphery of the ring 372, a cylindrical connecting shaft 376 disposed radially outwardly at the outer wall of the ring 372, and a cylindrical welding shaft 378 disposed coaxially with the connecting shaft 376. In some embodiments, the cylindrical welding shaft 378 may have a smaller diameter than the cylindrical connecting shaft 376, and the cylindrical connecting shaft 376 is fitted into the recessed opening 368 to allow the distal edge of the shaft 354 to be joined with the proximal edge of the cylindrical welding shaft 378, thereby allowing the two surfaces to be joined by welding (e.g., laser welding).

[0296] 32 and 33, in some embodiments, the shaft 354 and the ring curette blade 356 may include or be constructed of stainless steel type 17-4PH (630) per ASTM A564 or equivalent, UNS S17400. In some embodiments, the shaft 354 and the ring curette blade 356 may include or be constructed of one of a metal, a metal alloy, titanium, carbon steel, stainless steel, tool steel, chrome steel, or ceramic. In some embodiments, the weld shaft 378 of the ring curette blade 356 may be disposed within the recessed opening 368 at the distal end of the shaft 354 and joined by laser welding.

[0297] 34 illustrates a handle assembly 352 that may be used with a ring curette 350, a square curette 400, or a rake curette 430 according to aspects of the present embodiment. In general, the handle assembly 352 may comprise a cylindrical body 390, a number of protrusions 392 on the outer and bottom surfaces of the cylindrical body 390 disposed perpendicular to the longitudinal axis of the cylindrical body 390, a flat surface 394 along the top surface of the cylindrical body, and a circular opening 396 at the distal end of the cylindrical body 390. In some embodiments, the handle assembly 352 may include or be constructed of acrylonitrile butadiene styrene (ABS) or other plastic or polymeric material, or the like.

[0298] FIG. 35 illustrates a square curette assembly 400 according to aspects of the present embodiment. In general, the square curette assembly 400 may include a handle 402, a shaft 404 coupled to a distal end of the handle 402, and a square curette blade 406 coupled to a distal end of the shaft 404. In some embodiments, the shaft 404 may include a cylindrical rod having at least two bends 408, 410 such that the ends of the shaft are parallel to and offset from the main longitudinal axis of the shaft. In some embodiments, the shaft 404 may include the same structure as the shaft 354 shown in FIG. 32. In some embodiments, the square curette blade 406 includes at least two surgically sharp edges 412, 414 at the distal end of the square curette blade (shown in FIG. 36).

[0299] 36 shows a square curette blade 406 for a square curette assembly 400 according to aspects of the present embodiment. In general, the square curette blade 406 may include a ring 416 in the shape of a hollow rounded right-angle prism, at least two surgically sharp edges 412, 414 at the top and bottom edges of the ring distal to the right-angle prism, a cylindrical connecting shaft 422 positioned to face outward toward the outer wall of the ring at a location on the ring opposite the location of the two surgically sharp edges on the ring, and a cylindrical welding shaft 424 positioned coaxially with the connecting shaft 422. In some embodiments, the cylindrical welding shaft 424 may be smaller in diameter than the connecting shaft 422 and connected to the shaft 404 by laser welding, similar to the embodiment shown in FIG.

[0300] 35 and 36, in some embodiments, the shaft 404 and square curette blade 406 may include or be constructed of stainless steel type 17-4PH (630) per ASTM A564 or equivalent, UNS S17400. In some embodiments, the shaft 404 and square curette blade 406 may include or be constructed of one of a metal, a metal alloy, titanium, carbon steel, stainless steel, tool steel, chrome steel, or ceramic. In some embodiments, the weld shaft 424 of the square curette blade 406 may be disposed within the recessed opening 368 at the distal end of the shaft 354 and joined by laser welding.

[0301] 37 illustrates a rake curette assembly 430 according to aspects of the present embodiment. In general, the rake curette assembly 430 may comprise a handle 423, a shaft 434 coupled to a distal end of the handle 423, and a rake curette blade 436 coupled to a distal end of the shaft 434. In some embodiments, the shaft may comprise a cylindrical rod tapered to a smaller diameter near the distal end of the shaft 434. In some embodiments, the rake head blade 436 may comprise a tapered wedge having at least one surgically sharp edge 454. In some embodiments, the rake head blade 436 is positioned perpendicularly and radially away from the longitudinal axis of the shaft 434, and the surgically sharp edge 454 is positioned perpendicular to the longitudinal axis of the shaft 434, such that the rake curette comprises a hatchet-like tool rather than an axe-like tool.

[0302] 38 illustrates a rake shaft 434 for a rake curette assembly 430, according to aspects of the present embodiment. The rake shaft 434 includes a cylindrical rod 440, a flat section 442 at the proximal end of the shaft for mounting within the handle 432, a tapered section 444 where the diameter of the cylindrical rod 440 gradually decreases toward the distal end of the shaft, and a cylindrical welded shaft 446 of further reduced diameter disposed coaxially within the tapered section 444 of the shaft 434.

[0303] 39 illustrates a rake head blade 436 for a rake curette assembly 430, according to aspects of the present embodiment. Generally, the rake head blade 436 includes a wedge-shaped body 450 that decreases in thickness with increasing depth, a rounded top 456 with a cylindrical opening 452 for laser welding, and a surgically sharp edge 454 at the end of the wedge-shaped body.

[0304] 38 and 39, in some embodiments, the shaft 434 and the rake head blade 436 may include or be constructed of stainless steel type 17-4PH (630) per ASTM A564 or equivalent, UNS S17400. In some embodiments, the shaft 434 and the rake head blade 436 may include or be constructed of one of a metal, a metal alloy, titanium, carbon steel, stainless steel, tool steel, chrome steel, or ceramic. In some embodiments, the cylindrical weld shaft 446 of the shaft 434 may be inserted into a cylindrical opening 452 of the rake head blade 436 and joined by laser welding.

[0305] 40 shows a schematic diagram of a method 460 of preparing a cell-seeded matrix composition for use during an arthroscopic surgical procedure according to aspects of the present embodiment. In general, the method 460 may include selecting a size of a matrix cutter to fit the surgical site prepared in the previous method 330 by cutting and removing the cartilage surrounding the defect or lesion using a surgical cutting tool (step 462), placing the cell-seeded support matrix on a cutting mat with the cells on the matrix facing upward (step 464), placing the selected matrix cutter on the cell-seeded support matrix with the surgically sharp edge facing downward (step 466), applying a downward force to the upper surface of the matrix cutter using at least one of a hand, a mallet, a hammer, or other tool (step 468), and removing the matrix cutter and removing the uncut portion of the cell-seeded support matrix (step 470). In some embodiments, the remaining cut portion of the cell-seeded support matrix may include an oval or other shape that fits the shape of the matrix cutter.

[0306] 41A shows a diagram illustrating processing of a cell-seeded support matrix composition according to aspects of the present embodiment, in which a portion of cell-seeded support matrix 482 is placed on a cutting mat 480 with the cell-seeded side facing up, a matrix cutter 484 is placed on top of the cell-seeded support matrix 462 with the blade side facing down, and an operator is holding a mallet 486.

[0307] 41B shows a diagram illustrating processing of a cell-seeded support matrix composition according to aspects of the present embodiment, where the mallet and matrix cutter 484 are in contact at location 488, a downward force is applied through the mallet 486, and a pair of tweezers 490 is visible nearby.

[0308] 41C shows a diagram illustrating processing of the cell-seeded support matrix composition according to aspects of the present embodiment, in which the uncut portion of the cell-seeded support matrix 482 has been removed from the cutting mat 480, leaving a cut portion of the matrix 492, having a shape that fits into the matrix cutter 484. Tweezers 490 may be used to handle the cell-seeded support matrix pieces 482, 492.

[0309] 42 illustrates a top perspective view of a matrix cutter 500 according to aspects of the present embodiment. In general, the matrix cutter 500 may comprise an elliptical cylinder body 502, a stadium-shaped internal bore 504 aligned parallel to the semi-major axis of the elliptical cylinder body 502 and aligned longitudinally parallel to the longitudinal axis of the elliptical cylinder body 502, a flat top surface 506 of the elliptical cylinder body, at least two flat gripping notches 508 on opposing outer surfaces of the elliptical cylinder body, and a surgically sharp edge 510 around the bottom periphery of the elliptical cylinder body 502. In some embodiments, the matrix cutter 500 may include or be constructed of stainless steel type 17-4PH(630), UNSS17400, conforming to ASTM A564. In some embodiments, the matrix cutter 500 may include or be constructed of one of a metal, a metal alloy, titanium, carbon steel, stainless steel, tool steel, chrome steel, or ceramic. In some embodiments, dimensions or other information may be etched or printed on the flat top surface 506. The interior holes 504 may also be formed in an oval or elliptical shape.

[0310] 43 shows a bottom perspective view of a matrix cutter 500 according to aspects of the present embodiment. A surgically sharp edge 510 is visible along the bottom periphery of the cutter body 502. In some embodiments, a flat gripping notch 508 can be used to pick up or handle the matrix cutter 500.

[0311] 44 shows a schematic diagram of a method 520 of implanting a cell-seeded matrix composition according to aspects of this embodiment. Generally, the method 520 includes stopping fluid flow and removing the dam seal subassembly (step 521), drying the surgical site where the cartilage was previously cut and removed by aspirating, draining, and cleaning and drying the surgical site using a first applicator swab (step 522), picking up a pre-cut cell-seeded support matrix piece using tweezers by grasping an edge of the matrix (step 524), placing the cell-seeded support matrix over the delivery tip of the matrix shuttle device such that the matrix is ​​within the contour of the delivery tip and the cell-containing side of the matrix faces away from the delivery tip (step 526), ​​applying fibrin glue to the surgical site using an applicator tool, and This may include drying the surgical site with the attached cartilage (step 527), inserting a matrix shuttle device into a cannula at the surgical site (step 528), depressing a plunger on the matrix shuttle device to extend at least one antenna from within the delivery tip of the matrix shuttle device to extrude the cell-seeded support matrix and push it onto the surgical site (step 530), removing the matrix shuttle device from the cannula (step 532), and, if necessary, repositioning the cell-seeded support matrix using a second applicator swab and applying fibrin glue around the edges of the cell-seeded support matrix at the surgical site using the second applicator swab (step 534).

[0312] FIG. 45 illustrates a perspective view of a matrix shuttle device 540 with deployment wings 548 extended, according to aspects of the present embodiment. FIG. 46 illustrates a perspective view of a matrix shuttle device 540 with deployment wings 548 retracted, according to aspects of the present embodiment. With reference to both FIG. 45 and FIG. 46, generally, the matrix shuttle device 540 includes a shuttle body 542. At a distal end of the shuttle body 542 is a delivery tip 544. A plunger 554 is longitudinally disposed within the shuttle body 542 and protrudes from a proximal end of the shuttle body 542, the proximal end of the plunger 554 being provided with a flat disk portion 556 (e.g., a thumb rest or flange). At least two deployment wings 548 are disposed within the delivery tip 544 and attached to the plunger 554. At least two holes 550 are on a distal surface of the delivery tip 544. A spring 558 is disposed longitudinally inside the shuttle body 542 and attached to the plunger 554 (shown in FIG. 49). One or more finger grips 552 are disposed at the proximal end of the shuttle body 542. In some embodiments, forcing the plunger 554 longitudinally into the shuttle body 542 causes at least two deployment wings 548 to extend outwardly through at least two holes 550 in the delivery tip. In some embodiments, the proximal end of the spring 558 can be disposed or biased against a middle portion of the plunger 554 (e.g., disposed in contact with the cylindrical body 560). In some embodiments, the distal end of the spring 558 can be disposed or biased against an inner surface of the shuttle body (e.g., inner surfaces of the shells 562, 564). Pressing and releasing the plunger 554 compresses and expands the spring 558 longitudinally, respectively. In some embodiments, a spring retracts the at least two deployment wings into the at least two holes when the plunger is released.

[0313] In some embodiments, the spring 558 may be formed from stainless steel, type 302 stainless steel, and / or other metals. In some embodiments, the spring 558 may be about 1.25 inches long (or about 1 inch to 2 inches, or about 1 inch to 1.5 inches, or about 1.1 to 1.3 inches, or about 1.2 to 1.4 inches long). In some embodiments, the spring may have an outside diameter (OD) of about 0.36 inches (or about 0.3 to 0.4 inches, or about 0.25 to 0.5 inches) and an inner diameter of about 0.298 inches (or about 0.2 to 0.3 inches, or about 0.2 to 0.4 inches, where the inner diameter is less than the inner diameter of the spring).

[0314] 47 shows a side view of a delivery tip 544 of a matrix shuttle delivery device 540 with a cell-seeding support matrix 492 disposed across the delivery tip 544, according to aspects of the present embodiment. In some embodiments, the cell-seeding support matrix 492 may be cut using a matrix cutter according to method 460 and shaped like an oval or other shape. The arrow indicates the placement of the cell-seeding support matrix 492 across the delivery tip 544. In some embodiments, the delivery tip 544 may further comprise a cylindrical portion 543 connected to the shuttle body 542 at the proximal end of the delivery tip 544, a tapered portion 545 at the distal end of the delivery tip 544 that terminates in a flat edge 549, and an elliptical or oval contoured ledge 547 across the top and distal end of the delivery tip 544.

[0315] 48 shows a side view of the matrix shuttle device 540 with the deployment wings 548 extended and the plunger 554 depressed to deliver the cell-seeded support matrix 492 according to aspects of the present embodiment. An arrow near the plunger 554 indicates pushing the plunger 554 into the matrix shuttle device body 542. In some embodiments, the operator can use a thumb to push the plunger 554 and flat disk portion 556 while using one or more other fingers to pull the finger grip 552. As the plunger 554 is pushed, in some embodiments, the deployment wings 548 can extend out of the holes 550 at the distal end of the delivery tip 544. The extension of the deployment wings 548 can, in some embodiments, push the cell-seeded support matrix 492 out of the delivery tip 544.

[0316] 47 and 48, in some embodiments, the above-described movements can deliver a cell-seeded support matrix to a surgical site, as described in step 530 of method 520, and the surgical site can be treated by method 330. The shape of tapered portion 545 at the distal end of matrix shuttle device 540 allows for a minimized surface area, reducing the likelihood that cell-seeded support matrix 492 will adhere to, and potentially be damaged in the process of being delivered from, matrix shuttle device 540.

[0317] FIG. 49 shows an exploded perspective view of the parts of the matrix shuttle device 540 according to aspects of this embodiment. In addition to the above parts, in some embodiments, the shuttle body may include two shells 562, 564. In some embodiments, the plunger 554 includes a cylindrical body 560, a flat disk portion 556 at the proximal end of the cylindrical body 560, and a recess with a protruding pin 568 at the proximal end of the cylindrical body 560. In some embodiments, the protruding pin 568 includes a small cylinder disposed perpendicular to the longitudinal axis of the cylindrical body 560 and a round knob having a diameter larger than the diameter of the small cylinder. In some embodiments, the protruding pin 568 with the round knob may be inserted into a circular hole 572 (shown in FIG. 50) in the deployment wings 548 to attach the deployment wings 548 to the plunger 554, and compression of the plunger may actuate the deployment wings 548.

[0318] With further reference to Figures 45-49, the matrix shuttle body 542 and plunger 554 may include or be constructed of acrylonitrile butadiene styrene (ABS) or other polymeric or plastic materials or the like.

[0319] 50 shows a perspective view of a deployment wing 548 for use with a matrix shuttle device 540, according to aspects of this embodiment. In general, the deployment wing comprises a U-shaped body (570), at least two wing arms (574) comprising cylindrical rods extending parallel to and curving outward away from the U-shaped body (570), at least two rounded tips (576) at the distal ends of the at least two wing arms (574), and a circular hole at the proximal bottom of the U-shaped body (572). In some embodiments, the deployment wing 548 may comprise or be constructed of silicone or ethylene propylene diene monomer (EPDM) rubber, or other polymers, plastics, or equivalent materials. The two rounded tips 576 help prevent damage to the cell-seeding support matrix 492 (and / or cells disposed thereon) when the two wing arms 574 are deployed (or extended) to push the cell-seeding support matrix 492 out of the matrix shuttle device 540.

[0320] 49 and 50, each of the rounded tips 576 is angled outwardly from a centerline 577 of the deployment wings 548 at an angle of about 1 to about 20 degrees (e.g., about 5-10 degrees, about 3-20 degrees, about 5-18 degrees, about 6-12 degrees, about 15-20 degrees, about 10-15 degrees, about 2-6 degrees, about 3-30 degrees, 1-45 degrees, and other subranges therebetween). In some embodiments, when the deployment wings 548 are retracted within the shuttle body, the rounded tips 576 are compressed radially inward by the inner surfaces of the shells 562, 564. As the deployment wings 548 are deployed outward, the inherent resiliency of the deployment wings 548 causes the rounded tips to be forced radially outward (e.g., as shown by the arrows in FIG. 48 ), thereby forcing the support matrix 492 out of the distal delivery tip 544 of the matrix shuttle delivery device 540. Stated another way, when the rounded tips 576 are not compressed inwardly by the inner surface of the shuttle device 540 (i.e., when they are in the deployed position), the rounded tips 576 expand outward to their uncompressed shape (i.e., the shape shown in FIG. 50 ). Pressing the plunger 554 distally causes the rounded tips 576 to be deployed both distally as well as radially outward, thereby facilitating the release of the support matrix 492 from the tapered portion 545. Additionally, the radial outward action of rounded tip 576 (i.e., in addition to the distal movement of rounded tip 576) serves to spread support matrix 492 prior to application at the target site.

[0321] 51 illustrates a perspective view of an applicator tool 580 according to aspects of the present embodiment. Generally, the applicator tool 580 is comprised of a cylindrical rod 582, an applicator swab 584 adhesively attached to one end of the cylindrical rod 582, and an applicator tip 586 adhesively attached to the other end of the cylindrical rod 582. In some embodiments, the applicator swab 584 may comprise cotton or polyurethane foam or other similarly flexible absorbent material. In some embodiments, the applicator tip 586 may comprise soft silicone or other similarly flexible material. In some embodiments, the cylindrical rod 582 may comprise a plastic material. In some embodiments, the adhesive may comprise Loctite 4011 adhesive.

[0322] FIG. 52 shows a schematic diagram of an arthroscopic surgical method 600 for repairing a cartilage defect, according to aspects of the present embodiment. In general, the method 600 may include forming an incision in a joint of a patient's body near a cartilage defect (step 602), inserting a cannula assembly into the incision (step 604), measuring the cartilage defect in the joint using an arthroscopic measurement tool inserted through the cannula (step 606), preparing the cartilage area surrounding the cartilage defect (step 608), preparing and cutting a portion of the cell-seeded matrix composition using a matrix cutter tool to match the shape of the prepared cartilage area (step 610), placing the portion of the cell-seeded matrix composition over a delivery tip of a matrix shuttle delivery device (step 612), inserting the matrix shuttle delivery device through the cannula (step 614), depressing a plunger on the matrix shuttle delivery device to deploy at least two deployment wings from within the delivery tip, thereby forcing the portion of the cell-seeded matrix composition out of the delivery tip and onto the prepared cartilage area (step 616), and removing the matrix shuttle delivery device from the cannula (step 618).

[0323] In some embodiments, step 608 may include using a first cutting tool to define an area of ​​cartilage surrounding the cartilage defect, and using one or more additional surgical cutting tools to scrape, cut, debride, and / or remove cartilage within the area of ​​cartilage defined by the first cutting tool. In some embodiments, the cell-seeded matrix composition of step 610 may include chondrocytes seeded on one side of a bioabsorbable matrix. In some embodiments, in step 610, the side of the cell-seeded matrix composition having the chondrocytes faces away from the delivery tip of the matrix shuttle delivery device. In some embodiments, method 600 may include the further steps of applying fibrin glue to the treated cartilage prior to delivery of the cell-seeded matrix composition, applying fibrin glue around the edges of the cell-seeded matrix composition after the cell-seeded matrix composition is delivered to the treated cartilage, removing the cannula from the incision, and surgically closing the incision.

[0324] In some embodiments, the article system may include cells seeded on the surface of the matrix. In some embodiments, the cells may include allogeneic chondrocytes. In some embodiments, the cells may include cells obtained from a non-human source.

[0325] In some embodiments, the instrument system may include one or more tools for measuring the cartilage defect, cutting the cartilage, preparing the surgical site, cutting the cell-seeded support matrix, delivering and implanting the cell-seeded support matrix. In some embodiments, the instrument system may include custom cutters (including, for example, articulated arthroscopic cutting tools, ring curettes, square curettes, and rake curettes), matrix cutters, measuring tools, and / or cutting blocks. Additional tools and materials that the surgeon or user may use while providing surgical materials may include scissors, razor blades, scalpels, surgical mallets, and / or cutting needles.

[0326] In some embodiments, the instrument system can include a device that is or includes a custom cannula assembly. In some embodiments, the custom cannula assembly provided in the kit can have an inner diameter ranging from about 15 mm to about 20 mm. The custom cannula assembly can include an obturator, a dam seal subassembly, and / or a cannula body.

[0327] In some embodiments, the instrument system may include one or more tools for securing the implanted composition at the surgical site. In some embodiments, the tool for securing the implanted composition may include one or more probes. In some embodiments, the tool for securing the implanted composition may include an applicator tool.

[0328] In some embodiments, additional materials and tools that a surgeon or user may use to perform the methods of the present disclosure may include forceps, tweezers, Adson forceps, neurosurgical putty, sutures, sterile dishes, sterile flasks, sterile solutions, epinephrine, and / or sterile saline.

[0329] Those skilled in the art will appreciate that numerous variations and / or modifications may be made to the invention shown in the specific embodiments without departing from the spirit and scope of the invention as broadly described.

[0330] All publications, patent applications, patents, and other references mentioned herein are incorporated herein in their entirety by reference.In addition, the materials, methods, and examples are illustrative only and are not intended to be limiting.Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by those skilled in the art to which this disclosure belongs.Although similar or equivalent methods and materials to those described herein can be used in the practice or testing of this disclosure, suitable methods and materials are described herein.

[0331] Working Example Example 1: Treatment of defective parts This example (Example 1) describes the treatment of a knee cartilage defect at a surgical site to be treated using the techniques provided in this disclosure. First, the surgical site can be flushed and washed with isotonic saline. The cartilage defect and the cartilage surrounding the defect can be physically and visually assessed via an arthroscopic device (e.g., an arthroscopic camera) inserted into the first surgical site adjacent to the defect and through a cannula 96 placed at the site. Attention should be paid to discoloration, irregular surface areas, lack of normal elasticity, thinning of the cartilage, and / or destabilization or damage of the cartilage. After inspection, the size of the defect should be measured using an arthroscopic measuring probe 210. The arthroscopic measuring probe 210 is a tool with a retractable and rotatable ruler 218 at its distal end that is inserted into the cannula 96 placed at the surgical site. The surgeon or operator should measure the dimensions of the defect using the marks 232 on the ruler 218 in order to select the appropriate cutting tool in the next step.

[0332] After measuring the defect, the area of ​​cartilage surrounding the defect may be contoured and shaped using, for example, but not limited to, a set of surgical cutting tools inserted into the cannula 92 at the second surgical site. The first tool is an articulated arthroscopic cutting tool 270 having a curved, oval shaped blade 278 at its distal end. The size of the blade 278 should be selected based on the measurements so that the blade can completely surround the defect. Using the thumb slider 274 on the cutting tool 270, the operator or surgeon can adjust the bevel angle of the blade 278 and then drive the blade into the cartilage to form a defined contour 52 in the cartilage.

[0333] The defect must then be debridemented peripherally down to the subchondral bone and until a vertical wall of healthy, stable cartilage 52 surrounds the defect site. Debridement may be performed with a second, third, and / or fourth surgical cutting tool. These tools may include a ring curette 350, a square curette 400, and / or a rake curette 430. Each of these tools may be inserted through the cannula 92 and have at least one surgically sharp edge or blade attached to the end of the shaft and a handle protruding outside the cannula. These cutting tools may be manipulated by a user or operator to place the surgically sharp edge at the defect site to cut or scrape away the cartilage. All damaged and fibrous tissue on the defect bed must be removed. Care must be taken to minimize removal of healthy cartilage outside the contour formed by the shape defined by the articulated arthroscopic cutting tool 270. Care must also be taken to avoid penetration of the subchondral bone. The resulting exposed area of ​​subchondral bone 54 and surrounding stable cartilage 42 may form a well-defined shape 52, such as an oval, that fits the shape of the curved blade of an articulated arthroscopic cutting tool. In preparation for placing an implant into the defect at the surgical site, the knee joint may be drained of fluid by incision or suction. Excess fluid around the defect may also be dried using kitners ("peanuts"), which wick excess fluid away from the cartilage defect. Petechial bleeding from the subchondral bone may be stopped by compressing with neurosurgical putty saturated with diluted epinephrine (e.g., 1 cc of 1:1000 epinephrine diluted in 20 cc of sterile saline) or by applying fibrin sealant to the bleeding site.

[0334] Example 2: Preparation of cell-seeded support matrix The cell-seeded support matrix needs to be prepared by cutting it to the appropriate size and shape before delivery and implantation at the surgical site. In Example 1 above, the defect site was treated by forming a well-defined shape 52 of exposed subchondral bone area with surrounding stable cartilage. The next step is to prepare a piece of cell-seeded support matrix that fits the shape of the treated defect site, so that it can be placed to cover the subchondral bone with minimal gaps or overlaps. A matrix cutter 500 can be selected that has dimensions and shapes that fit the treated site. A piece of cell-seeded support matrix 482 can be placed on a cutting mat 480 with the cells facing up. The cutting mat 480 may be made of a soft, flexible material such as silicone or rubber. To avoid damage to the cells, the cells should face up and have minimal contact with the cell-seeded surface. The matrix cutter 500 is then placed on the cell-seeded support matrix 482 with the blade side 510 facing down. A user or operator then applies a downward force to the top surface 506 of the matrix cutter 500 using at least one of a hand, a hammer, a mallet 486, and / or other tool. The downward force causes the blade 510 of the matrix cutter 500 to cut into the cell-seeded support matrix 482 in a manner similar to how a cookie cutter cuts cookies from a sheet of dough. The matrix cutter 500 can then be removed and the portion of the cell-seeded support matrix that has been cut to the same shape 492 as the matrix cutter 500 can be retrieved by tweezers 490 and / or other handling tools. To minimize damage to the cells, handling of the cell-seeded support matrix should occur primarily at the cut edges.

[0335] Example 3: Delivery of cell-seeded support matrix using a matrix shuttle delivery device Following preparation of the cell-seeded support matrix 492 by cutting with the matrix cutter tool 500 shown in Example 2, the cell-seeded support matrix 492 can be delivered to the surgical defect site prepared in Example 1. The user or operator can pick up the prepared cell-seeded support matrix 492 with tweezers to gently grab one or more edges, taking care to minimize contact with the matrix interior and to handle the matrix gently to minimize damage to the cells. The cell-seeded support matrix 492 can then be carefully placed, cell-seeded side facing up, over the distal delivery tip 544 of the matrix shuttle delivery device 540. The delivery tip 544 has a contour 547 engraved as a recess to match the shape and size of the prepared cell-seeded support matrix. Matrix shuttle delivery devices are available in different sizes to accommodate different sizes of cell-seeded support matrix pieces. The delivery tip also has a narrow flat tip area 549 at its most distal end to minimize the contact area between the device and the cell-seeded support matrix 492. The cell-seeding support matrix 492 remains in contact with the matrix shuttle delivery device 540 by capillary forces due to moisture between the shuttle and the matrix, and no additional mechanism for attachment is required.

[0336] Next, the matrix shuttle delivery device 540 with the cell-seeded support matrix 492 disposed in the delivery tip 544 is inserted into the cannula 92 at the surgical site. The user or operator must then move and rotate the matrix shuttle delivery device 540 to position the delivery tip 544 so that the cell-seeded support matrix 492 is closely aligned with the treated defect site 52. The plunger 556 on the matrix shuttle delivery device 540 is then pushed into the body of the matrix shuttle delivery device 540 by the user or operator using the finger grip to provide opposing force. As the plunger 556 is pushed, at least two deployment wings 548 in the delivery tip 544 protrude outward from at least two holes 550 and push against the cell-free bottom side of the cell-seeded support matrix 492. The tips 576 of the deployment wings 548 are rounded and have a small radius to minimize the contact area with the cell-seeded support matrix 492. The cell-seeded support matrix 492 is then pushed out of the delivery tip 544 of the matrix shuttle delivery device 540 and into the prepared defect site 52. The cell-seeded side of the matrix should be in contact with the exposed subchondral bone of the prepared defect site. The user or operator can use the applicator tool 580 to gently reposition the cell-seeded support matrix 492 so that it is properly aligned within the prepared defect site 52.

[0337] Example 4: Fixation of cell-seeded support matrix in cartilage defect This example (Example 4) describes a method for fixing a cell-seeded support matrix 492 to a defect at a surgical site. The cell-seeded support matrix 492 can be fixed using a fibrin glue fixation step that can be performed following arthroscopic delivery of the cell-seeded support matrix 492 to the defect in a patient. After the cell-seeded support matrix 492 is inserted into the defect, a fibrin sealant (such as Tisseel®, a fibrin-based adhesive available from Baxter, Austria) can be applied to the edges (i.e., periphery) of the implant with the cell-seeded side of the implant facing the defect. Light pressure can then be applied using an applicator tool 580 or another tool.

[0338] The safety of the implant should be tested by fully flexing and extending the knee several times to ensure that the implant remains in place. The joint may then be cleaned and irrigated to remove any loose particles of bone or cartilage remaining at the site. Care should be taken to ensure that the implant is protected during irrigation and does not become dislodged. The wound can then be closed using standard techniques known to those skilled in the art.

[0339] In general, the above examples illustrate how arthroscopic surgery can be performed on a knee joint to repair a cartilage defect using the present embodiment. The defect site is measured using an arthroscopic measuring tool 210. An appropriately sized cutting tool 270 is selected and used to cut a contour around the defect. The defect site is prepared using one or more surgical cutting tools to remove damaged cartilage and form a well-defined area 52 of exposed subchondral bone surrounded by healthy cartilage. A portion of the cell-seeded support matrix 492 is cut with a matrix cutter 500 to prepare it to the size and shape of the prepared defect site 52. The cell-seeded support matrix 492 is delivered to the defect site using a matrix delivery shuttle device 540 to minimize contact with and damage to the cells. The cell-seeded support matrix 492 is then secured using fibrin glue, the joint is cleaned and irrigated, and the wound site is closed.

[0340] Example 5: Cell viability bench test In this example (Example 5), the delivery methods described in Examples 3, 4, and 5 are compared based on their effect on cell number and viability after simulating delivery to a defect at a surgical site in knee joint tissue. The experiment was performed using a human anatomical knee model. Positive controls included a condition in which the cell-seeded matrix was not delivered to the site in any way, and a condition in which the cell-seeded matrix was delivered to the site using conventional open surgical techniques.

[0341] Delivery of cell-seeded support matrix implants via the methods, tools, and devices disclosed herein resulted in the unexpected and surprising result of improved cell number and cell viability values ​​compared to conventional surgical methods, as measured qualitatively.

[0342] As a qualitative visual measure of cell viability, cellular metabolic activity was measured by staining cells on the matrix with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and visually inspecting for insoluble formazan-positive cells, a dark conversion product characteristic of actively respiring cells. Compared to other methods tested, matrices delivered using the current method and tools retained the highest number of metabolically active cells, approaching the number of undelivered positive control matrices. The MTT assay also showed that minimizing contact and handling of the cell-seeded support matrix was important to achieve the highest cell viability across the cell-seeded support matrix.

[0343] Conventional methods for implanting MACI (and / or cell-seeded support matrix 492) result in less than 4% cell viability using arthroscopic methods and less than 40% cell viability using open techniques (see Biant et al. (Biant, LC, Simons, M., Gillespie, T. and McNicholas, MJ, 2017. Cell viability in arthroscopic versus open autologous chondrocyte implantation. The American Journal of Sports Medicine, 45(1), pp. 77-81.)). [Table 1]

[0344] Table 1 includes results of bench testing using the devices and methods described herein. The table includes a summary of minimum cell count (MCN) and cell viability results from various exemplary steps including delivery of cell-seeded matrix 492 by shuttle delivery device 540, manipulation of cell-seeded matrix 492 by silicone tip 586 (also shown in some embodiments as applicator tip), and manipulation of cell-seeded matrix 492 by sponge tip 584 (also shown in some embodiments as applicator swab). MCN and cell viability were also reported for control experiments in which various pressures (e.g., from about 370 grams to about 1635 grams) were applied to cell-seeded matrix 492 with a thumb for 30 seconds. In all cases, both minimum cell count (MCN, measured in relative fluorescence units (RFU)) and cell viability (measured in percentage and assessed as an overall average) met the relevant acceptance criteria (i.e., greater than 5000 RFU and 80% or greater cell viability, respectively). Note that all cell viability values ​​were within the range of 94%-99%.

[0345] Equivalent Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, many equivalents to the specific embodiments of the invention described herein. The scope of the invention is not intended to be limited to the above Description, but rather is as set forth in the following claims.

Claims

1. a shuttle body, the shuttle body comprising a substantially hollow cylinder; a delivery tip at a distal end of the shuttle body; a plunger disposed longitudinally within the shuttle body and projecting from a proximal end of the shuttle body; at least two deployment wings disposed within the delivery tip and attached to the plunger; at least two holes on a distal surface of the delivery tip, The matrix shuttle delivery device, wherein pressing the plunger longitudinally into the shuttle body causes the at least two deployment wings to extend outwardly through the at least two holes in the delivery tip.

2. 10. The matrix shuttle delivery device of claim 1, further comprising a spring disposed longitudinally within the shuttle body and attached to the plunger.

3. The matrix shuttle delivery device of claim 1 , further comprising one or more finger grips disposed at the proximal end of the shuttle body.

4. 4. The matrix shuttle delivery device of claim 3, wherein the one or more finger grips each comprise a rod having one end connected to an outer surface of the shuttle body and extending radially outward from the shuttle body, the distal side of each rod being curved to accommodate a user's finger.

5. The delivery tip comprises: a cylindrical portion connected to the shuttle body at a proximal end of the delivery tip; a tapered section including two sloping sides that meet at a flat surface at a distal end of the delivery tip; a contoured ledge around the distal end of the delivery tip that comprises an elliptical or oval shape; The matrix shuttle delivery device of claim 1 , wherein a centerline of the contoured ledge is substantially parallel to the flat surface at the distal end of the delivery tip.

6. 6. The matrix shuttle delivery device of claim 5, wherein the at least two holes are respectively disposed on the two sloping side surfaces of the delivery tip, such that when the deployment wings are extended, a line connecting the rounded tips of the deployment wings is substantially perpendicular to the flat surface at the distal end of the delivery tip.

7. The matrix shuttle delivery device of claim 1 , wherein each of said at least two holes comprises a diameter greater than a diameter of each of said at least two deployment wings.

8. The deployment wing includes: A U-shaped body; at least two wing arms extending parallel from the U-shaped body and including cylindrical rods curving outwardly away from the U-shaped body; at least two rounded tips at a distal end of the at least two wing arms; a circular hole at the proximal bottom of the U-shaped body; 2. The matrix shuttle delivery device of claim 1 comprising:

9. 10. The matrix shuttle delivery device of claim 1, wherein said deployment wings comprise at least one member from the group consisting of silicone, ethylene propylene diene monomer (EPDM) rubber, plastic, and flexible polymeric materials.

10. The plunger is A cylindrical body; a flat disk portion at a proximal end of the cylindrical body; a recess with a protruding pin at the proximal end of the cylindrical body; 9. The matrix shuttle delivery device of claim 8, wherein the ejector pin comprises a small cylinder disposed perpendicular to the longitudinal axis of the cylindrical body and a rounded knob having a diameter larger than the diameter of the small cylinder.

11. The matrix shuttle delivery device of claim 10 , wherein the ejection pin of the plunger passes through the circular hole in the proximal bottom of the U-shaped body of the deployment wing.

12. 10. The matrix shuttle delivery device of claim 1, wherein the plunger and the shuttle body comprise at least one of acrylonitrile butadiene styrene (ABS) or plastic.

13. The matrix shuttle delivery device of claim 3 , wherein the shuttle body, the delivery tip, and the finger grip are formed as two continuous identical shells that collectively form the matrix shuttle delivery device.

14. The matrix shuttle delivery device of claim 2 , wherein the spring retracts the at least two deployment wings into the at least two holes when the plunger is released.

15. An arthroscopic measurement probe (210), comprising: a handle (212) including a top shell piece (211) and a bottom shell piece (213); An adjustment knob (214); A rotating plug (222); Dowel pin (224), A stroke arm (226); A sizer tube (216); A flexible ruler (218); the rotating plug, the adjustment knob, the stroke arm, the sizer tube, and the flexible ruler are coaxially connected; The arthroscopic measurement probe (210), wherein the flexible ruler is disposed through an interior of the sizer tube.

16. The flexible ruler (218) a cylindrical rod (230) comprising polyetheretherketone (PEEK); an inner flexible wire comprising nickel titanium (or nitinol); a plurality of marks (232) distributed along a length of an outer surface of the cylindrical rod near a distal end of the cylindrical rod (230); 16. The measurement probe of claim 15, wherein the marks (232) comprise thin lines perpendicular to a longitudinal axis of the cylindrical rod (230) and spaced apart at 2.5 mm and 5.0 mm intervals.

17. The sizer tube is a hollow cylindrical tube (234) comprising at least one of stainless steel T304, stainless steel T316, and fractional hypodermic tubing; two diametrically opposed slits (236) disposed at a proximal end of the hollow cylindrical tube; a curved portion (238) of said hollow cylindrical tube (234) at a distal end, said curve including a right angle bend within said tube; an opening (240) at the distal end of the hollow cylindrical tube (234); The measurement probe of claim 15 , comprising:

18. The measurement probe of claim 15, wherein the top shell piece (211) and the bottom shell piece (213) comprise acrylonitrile butadiene styrene (ABS) or other similar plastic.

19. 1. An articulated arthroscopic cutting tool (270), comprising: A handle (272); Sam Slider (274) and A linear stator shaft (276); a curved elliptical blade (278) connected to said linear stator shaft (276) by a hinge joint (280); a linear transmission shaft (292) connected to the thumb slider (274); a link piece (282) connected to both the linear transmission shaft (292) and the curved elliptical blade (278); The articulated arthroscopic cutting tool (270), wherein movement of the thumb slider (274) causes the curved elliptical blade (278) to tilt relative to the linear stator shaft (276).

20. The handle (272) is an upper shell (286) comprising a ridged semi-cylinder and a rectangular opening (290) cut longitudinally along said ridged semi-cylinder proximate a distal end thereof; a lower shell (288) comprising a semi-cylinder with projections; said upper shell and said lower shell are closed together to form a complete cylinder having a circular opening (298) at said distal end; The cutting tool of claim 19, wherein a plurality of notches are disposed on the underside of the top shell (286) about the rectangular opening (290).

21. 21. The handle of claim 20, wherein the upper and lower shells comprise acrylonitrile butadiene styrene (ABS) or an equivalent plastic.

22. The thumb slider is a slide button (274) including a raised top surface at a distal end of the button and a protruding top surface at a proximal end of the button; A slider clamp piece (296); a spring (294) attached at one end to the slide button (274) and at the other end to the slider clamp piece (296), the spring (294) being disposed vertically between the slide button (274) and the slider clamp piece (296); 20. The cutting tool of claim 19, wherein a cylindrical pin (275) actuated by the slide button (274) is capable of interfacing with the plurality of notches in the underside of the top shell (286).

23. The linear stator shaft (276) A cylindrical rod (300); a rectangular groove (302) cut longitudinally along said cylindrical rod; a reduced diameter section (304) along said cylindrical rod (300) near a proximal end of said cylindrical rod (300); a circular ring (306) projecting perpendicularly from the distal end of the cylindrical rod; 20. The cutting tool of claim 19, comprising:

24. The linear stator shaft of claim 23, wherein the linear stator shaft comprises stainless steel type 17-4PH(630), UNS S17400, conforming to ASTM A564.

25. The curved elliptical blade (278) An oval ring (310); at least three crossbar pieces (312, 314, 316) spanning across an upper surface of the elliptical ring (310); a circular ring (318) extending perpendicularly from said first crossbar piece; Two circular rings (320) extending perpendicularly from the second crossbar piece; a curved cut surface (322) along a bottom periphery of the elliptical ring; the elliptical ring is thicker at a narrow end of the elliptical ring; The cutting tool of claim 19 , wherein the curved cutting surface includes a surgically sharp edge.

26. 26. The curved oval blade of claim 25, wherein the curved oval blade comprises stainless steel type 17-4PH (630), UNS S17400, conforming to ASTM A564.

27. a shuttle body, the shuttle body comprising a substantially hollow cylinder; a delivery tip at a distal end of the shuttle body, a cylindrical portion connected to the shuttle body at a proximal end of the delivery tip; a tapered section including two sloping sides that meet at a flat surface at a distal end of the delivery tip; a contoured ledge across a top and distal end of the delivery tip comprising an elliptical or oval shape; a plunger disposed longitudinally within the shuttle body and projecting from a proximal end of the shuttle body, the plunger comprising: A cylindrical body; a flat disk portion at a proximal end of the cylindrical body; a recess with a protruding pin at the proximal end of the cylindrical body; the plunger, wherein the ejector pin comprises a small cylinder disposed perpendicular to the longitudinal axis of the cylindrical body and a rounded knob having a diameter greater than the diameter of the small cylinder; A matrix shuttle delivery device comprising:

28. At least two deployment wings disposed within the delivery tip and attached to the plunger, the deployment wings comprising: A U-shaped body; at least two wing arms extending parallel from the U-shaped body and including cylindrical rods curving outwardly away from the U-shaped body; at least two rounded tips at a distal end of the at least two wing arms; a circular hole at the proximal bottom of the U-shaped body; The deployable wing comprises: one or more finger grips disposed at the proximal end of the shuttle body; 28. The matrix shuttle delivery device of claim 27, further comprising: at least two holes, each hole disposed on one of the two angled sides of the delivery tip; a spring disposed longitudinally inside the shuttle body and attached to the plunger; Further comprising: pressing the plunger longitudinally into the shuttle body causes the at least two deployment wings to exit the at least two holes in the delivery tip; the device, when the plunger is released, causes the spring to retract the at least two deployment wings into the at least two holes.

29. 1. An arthroscopic surgical method for repairing a cartilage defect, comprising: making an incision in a joint of a patient's body proximate the cartilage defect; Inserting a cannula assembly into the incision; measuring the cartilage defect in the joint using an arthroscopic measurement tool inserted through the cannula; Treating the cartilage area surrounding the cartilage defect; and using a matrix cutter tool to manipulate and cut a portion of the cell-seeded matrix composition to conform to the shape of the manipulated cartilage region; disposing a portion of the cell-seeded matrix composition over a delivery tip of a matrix shuttle delivery device; inserting the matrix shuttle delivery device through the cannula; depressing a plunger on the matrix shuttle delivery device to deploy at least two deployment wings from within the delivery tip, thereby forcing a portion of the cell-seeded matrix composition out of the delivery tip and onto the treated cartilage region; removing the matrix shuttle delivery device from the cannula; The method comprising:

30. Treating the cartilage area includes: using a first cutting tool to define a region of cartilage surrounding the cartilage defect; using one or more additional surgical cutting tools to scrape, cut, debride, and / or remove cartilage within the area of ​​the cartilage defined by the first cutting tool; 30. The method of claim 29, comprising:

31. 30. The method of claim 29, wherein the cell-seeded matrix composition comprises chondrocytes seeded on one side of a bioabsorbable matrix, the side of the matrix having chondrocytes facing away from the delivery tip of the matrix shuttle delivery device.

32. applying a fibrin glue to the treated cartilage prior to delivery of the cell-seeded matrix composition; applying fibrin glue around the edges of the cell-seeded matrix composition after the cell-seeded matrix composition has been delivered to the treated cartilage; removing the cannula from the incision; surgically closing the incision; and 30. The method of claim 29, further comprising:

33. A cannula body (96); a dam seal subassembly (94) disposed proximally from the cannula body, the dam seal subassembly (94) and the cannula body (96) being coaxially aligned; an obturator (92) coaxially inserted into both the cannula body (96) and the dam seal subassembly (94); A cannula assembly (90).

34. The cannula body (96) a hollow cylindrical portion (120) including a helical thread (126) wrapping around the entire length of an outer surface of the hollow cylindrical portion (120); a lip portion (122) at a proximal end of the hollow cylindrical portion (120), the lip portion (122) including a diameter greater than a diameter of the hollow cylindrical portion (120); two diametrically opposed tabs (128) located on the outer edge of said lip portion (122); a curved opening (130) at the distal end of the hollow cylindrical portion (120); 34. The assembly of claim 33, comprising:

35. 35. The cannula body of claim 34, wherein the curved opening (130) is marked by a visible outline around a periphery of the curved opening and by two small visible marks (132) diametrically opposed to each other around the curved opening.

36. The assembly of claim 33, wherein the cannula body (96) comprises a translucent polycarbonate material.

37. The dam seal subassembly (94) A dam upper piece (148); a first dam seal (154) including at least one hole; a second dam seal (156) including at least one slit; a third dam seal (158) including at least one slit; and a dam bottom piece (150); 34. The assembly of claim 33, wherein the dam top piece (148), the first dam seal (154), the second dam seal (156), and the third dam seal are all coaxially aligned (or longitudinally or axially aligned) and stacked parallel to one another.

38. The dam top piece (148) a circular portion (151) containing concentrically arranged circular holes (154) therein; a plurality of legs (152) extending perpendicularly from the bottom surface of the circular portion and distributed circumferentially around the circular portion (151); two notches (112) located diametrically opposite each other around said circular hole (154); 38. The subassembly of claim 37 comprising:

39. 38. The subassembly of claim 37, wherein the dam top piece and the dam bottom piece comprise acrylonitrile butadiene styrene (ABS).

40. The first dam seal (154) A circular disk (173); a circular hole (176) concentrically disposed in the center of said circular disk; a plurality of smaller circular holes (174) arranged circumferentially around the edge of said disk; 38. The subassembly of claim 37 comprising:

41. The second dam seal and the third dam seal each include A circular disk (171); three slits (172) spaced apart from each other by 120 degrees along the radial direction from the center of the circular disk; a plurality of smaller circular holes (170) arranged circumferentially around the edge of said circular disc (171); Equipped with 38. The subassembly of claim 37, wherein the second dam seal and the third dam seal are coaxially stacked on top of each other and rotated such that the slits of each seal do not overlap.

42. 38. The subassembly of claim 37, wherein the first dam seal, the second dam seal, and the third dam seal all comprise one of a silicone rubber or an EPDM rubber.

43. The dam bottom piece (140) comprises: A hollow cylindrical portion (150); a flat circular top portion (146); a circular hole (144) concentrically disposed in said flat circular top portion (146); two depressions (112) arranged diametrically opposite each other around said circular hole (144); two dam release clips diametrically disposed on a distal edge of said hollow cylindrical portion; 38. The subassembly of claim 37 comprising:

44. 38. The subassembly of claim 37, wherein the dam top piece and the dam bottom piece comprise acrylonitrile butadiene styrene (ABS) or equivalent.

45. The obturator comprises: a handle portion (100) at the proximal end of the obturator; A shaft portion (104); a tip (106) at a distal end of the obturator; The handle portion (100) includes a rounded dome-shaped structure with slats (102) of constant thickness aligned parallel to and perpendicular to the axial direction; the shaft portion (104) comprises a cylindrical rod connecting the handle portion and the tip portion; The tip (106) comprises a conical tip at the distal end and a plurality of support fins (108); 34. The assembly of claim 33, wherein the handle portion, the shaft portion, and the tip portion are all coaxially aligned (or longitudinally or axially aligned).

46. The obturator comprises: two or more rotation tabs (110) projecting from a bottom distal end of said handle portion (100) diametrically opposed to one another; one or more concave portions (180) in the dome-shaped structure of the handle portion; 34. The assembly of claim 33, comprising:

47. 34. The assembly of claim 33, wherein the obturator comprises acrylonitrile butadiene styrene (ABS) or equivalent.

48. An arthroscopic surgery method (10), comprising: Making an incision in a joint of a patient's body; Inserting a cannula assembly into the incision; measuring a cartilage defect in the joint using an arthroscopic measurement tool inserted through the cannula; Treating the cartilage area surrounding the cartilage defect; and using a matrix cutter tool to manipulate and cut a portion of the cell-seeded matrix composition; The method comprising:

49. Treating the cartilage area includes: scoring the endochondral area surrounding the defect using a cutter tool; debride the scored area using one or more cutting and scraping tools to expose a bone surface in a defined area or shape; drying the exposed bone area using an applicator tool; 49. The method of claim 48, further comprising:

50. 49. The method of claim 48, wherein the joint site may include one of the medial femoral condyle, the lateral femoral condyle, the patella, or the trochlea.

51. 49. The method of claim 48, wherein debriding the incision area further comprises using at least one of a ring curette, a square curette, or a rake curette.

52. 1. A method (200) for determining lesion size during arthroscopic surgery, comprising: inserting a measurement tool into the cannula through the dam seal subassembly; extending a ruler from the measurement tool; measuring at least one dimension of at least one lesion using at least one or more marks on the ruler; Retracting the ruler into the measurement tool; removing the measurement tool from the cannula and the dam seal subassembly; The method comprising:

53. 1. A method (250) for scoring cartilage using an articulated arthroscopic cutting tool, comprising: selecting an articulated arthroscopic cutting tool based on the measured dimensions of the defect or lesion; removing the dam seal subassembly from the cannula; Inserting an articulated arthroscopic cutting tool into the cannula; Using a thumb slider to adjust the tilt angle of the blade; locking the tilt angle; forcing the blade into the area of ​​cartilage surrounding the defect; removing the articulated arthroscopic cutting tool from the cannula; The method comprising:

54. 1. A method for removing cartilage and preparing a surgical site, comprising: inserting a surgical cutting tool selected from at least one of a ring curette, a square curette, or a rake into the cannula and dam seal subassembly; using a surgical cutting tool to scrape, cut, debride, and remove cartilage within an area of ​​cartilage defined by the arthroscopic cutting tool; removing the cutting tool from the cannula and the dam seal subassembly; repeating the procedure with one or more surgical cutting tools until the cartilage within the region of cartilage is completely removed; The method comprising:

55. A ring curette assembly (350), comprising: A handle (352); a shaft (354) coupled to a distal end of the handle; a ring curette blade (356) coupled to a distal end of the shaft; the shaft (354) comprises a cylindrical rod having at least two bends (362, 364) such that the distal end of the shaft has an axis parallel to and eccentric from a main longitudinal axis of the shaft; The ring curette assembly (350), wherein the ring curette blade (356) includes at least one surgically sharp edge (374).

56. The shaft (354) A cylindrical rod (358); a flat portion (360) at a proximal end of said cylindrical rod (358) for mounting within said handle (352); a first bend (362) in the cylindrical rod (358) near a distal end of the rod such that the rod axis is angled away from a primary longitudinal axis of the cylindrical rod; a second bend (364) of the cylindrical rod (358) further near the distal end of the rod such that the rod axis is angled parallel to and eccentrically disposed from the main longitudinal axis of the cylindrical rod; a cylindrical portion (366) of reduced diameter near the distal end of the rod; a recessed opening (368) at the distal end of the shaft having a flat inner surface; 56. The ring curette assembly of claim 55, comprising:

57. The ring curette blade is A hollow right circular truncated cone-shaped ring (372); a rounded edge (370) around the larger periphery of said ring (372); a surgically sharpened edge (374) around the larger periphery of the ring (372); a cylindrical connecting shaft (376) disposed radially outwardly on the outer wall of said ring (372); a cylindrical welding shaft (378) arranged coaxially with the connecting shaft (376); 56. The ring curette assembly of claim 55, wherein said cylindrical welding shaft (378) is smaller in diameter than said cylindrical connecting shaft (376).

58. 56. The ring curette assembly of claim 55, wherein said shaft (354) and said ring curette blade (356) comprise stainless steel type 17-4PH (630) per ASTM A564 or equivalent, UNS S17400.

59. The handle (352) is A cylindrical body (390); a plurality of protrusions (392) on an outer surface and a bottom surface of the cylindrical body (390) disposed perpendicular to a longitudinal axis of the cylindrical body (390); a flat surface (394) along the top surface of said cylindrical body; a circular opening (396) at a distal end of said cylindrical body; 56. The ring curette assembly of claim 55, comprising:

60. 56. The ring curette assembly of claim 55, wherein said handle (352) comprises acrylonitrile butadiene styrene (ABS) or equivalent.

61. A square curette assembly (400), comprising: A handle (402); a shaft (404) coupled to a distal end of the handle; a square curette blade (406) coupled to a distal end of the shaft (404); the shaft (404) comprises a cylindrical rod having at least two bends (408, 410) such that the distal end of the shaft has an axis parallel to and eccentric from a main longitudinal axis of the shaft; The quadrangular curette assembly (400), wherein the quadrangular curette blade (406) includes at least two surgically sharp edges (412, 414) at a distal end of the quadrangular curette blade.

62. The square curette blade is A ring (416) in the form of a hollow rounded rectangular prism; at least two surgically sharpened edges (412, 414) on the top and bottom edges of the ring (416) distal to the right angle prism; a cylindrical connecting shaft (422) facing outwardly at the outer wall of said ring (416) and disposed opposite said two surgically sharp edges (412, 414); a cylindrical welding shaft (424) arranged coaxially with the connecting shaft (422); 62. The square curette assembly of claim 61, wherein the cylindrical welding shaft (424) is smaller in diameter than the connecting shaft (422).

63. 63. A square curette assembly as defined in claim 62, wherein said shaft and said square curette blade comprise stainless steel type 17-4PH (630) per ASTM A564 or equivalent, UNS S17400.

64. A rake curette assembly (430), comprising: A handle (432); a rake shaft (434) coupled to a distal end of the handle (432); a rake head blade (436) coupled to a distal end of said shaft (434); The rake shaft (434) comprises a cylindrical rod tapered to a smaller diameter near a distal end of the shaft (434); The rake curette assembly (430), wherein the rake head blade (436) includes a tapered wedge having at least one surgically sharp edge (454).

65. The rake shaft (434) A cylindrical rod (440); a flat portion (442) at the proximal end of the shaft for mounting within the handle (432); a tapered section (444) in which the diameter of said cylindrical rod (440) gradually decreases towards the distal end of said rake shaft (434); a cylindrical weld shaft (446) of further reduced diameter disposed coaxially with the tapered portion (444) of the rake shaft (434); 65. The rake curette assembly of claim 64 comprising:

66. The rake head blade is a wedge-shaped body (450) having a thickness that decreases with increasing depth; a rounded top portion (456) having a cylindrical opening (452) for welding; a surgically sharp edge (454) at the end of said wedge-shaped body (450); 65. The rake curette assembly of claim 64, comprising:

67. 65. The rake curette assembly of claim 64, wherein said shaft and said rake head blade (436) comprise stainless steel type 17-4PH (630) conforming to ASTM A564 or equivalent, UNS S17400.

68. 1. A method for cutting a cell-seeded support matrix (460), comprising: Selecting a size of matrix cutter to fit the surgical site to be treated by cutting and removing cartilage surrounding the defect or lesion; Placing a cell-seeding support matrix on a cutting mat with the cells on the matrix facing upward; placing the selected matrix cutter onto the cell-seeded support matrix with a surgically sharp edge facing downward; applying a downward force to an upper surface of the matrix cutter using at least one of a hand, a mallet, a hammer, or other tool; Removing the matrix cutter and removing the uncut portion of the cell-seeding support matrix; The method comprising:

69. A matrix cutter comprising: An elliptical cylindrical body (502); a stadium-shaped internal bore (504) aligned parallel to a semi-major axis of the elliptical cylindrical body (502) and longitudinally aligned parallel to the longitudinal axis of the elliptical cylindrical body (502); A flat upper surface (506) of the elliptical cylindrical body; at least two flat gripping notches (508) on opposing exterior surfaces of the elliptical cylindrical body; a surgically sharpened edge (510) around the bottom periphery of said elliptical cylindrical body (502); The matrix cutter.

70. 70. The matrix cutter of claim 69, wherein the matrix cutter comprises stainless steel type 17-4PH (630), UNS S17400, conforming to ASTM A564.

71. 1. A method for delivering and implanting a cell-seeded support matrix into a treated cartilage surgical site (520), comprising: stopping fluid flow and removing the dam seal subassembly at the surgical site; using a first applicator swab to cleanse and dry the surgical site where cartilage was previously cut and removed around the lesion or defect; using tweezers to pick up a pre-cut piece of cell-seeded support matrix by grasping an edge of said matrix; placing the cell-seeded support matrix over a delivery tip of a matrix shuttle delivery device such that the matrix is ​​within the contour of the delivery tip and a cell-containing side of the matrix faces away from the delivery tip; applying fibrin glue to the surgical site using a second applicator swab; inserting the matrix shuttle delivery device into a cannula at the surgical site; depressing a plunger on the matrix shuttle device to deploy at least one antenna from within the delivery tip of the matrix shuttle device, thereby extruding the cell-seeded support matrix and forcing it onto the surgical site; removing the matrix shuttle device from the cannula; Optionally, repositioning said cell-seeded support matrix using a third applicator swab; applying fibrin glue around the edges of the cell-seeded support matrix at the surgical site using a fourth applicator swab; The method comprising:

72. An applicator tool (580), A cylindrical rod (582); an applicator swab (584) attached by adhesive to one end of said cylindrical rod (582); an applicator tip (586) attached by adhesive to another end of the cylindrical rod (582); said cylindrical rod (582) comprising a plastic material; said applicator swab (584) comprising cotton, polyurethane foam, or other similarly flexible, absorbent material; The applicator tool (580), wherein the applicator tip (586) comprises a flexible silicone or other similar flexible material.

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