Methods and kits for treating damaged connective tissue

Abstract

The growth or regeneration of the damaged connective tissue in the subject is achieved through a combination of the application of a support matrix and blood taken from the subject, where the blood is introduced between the support matrix and the damaged area of ​​the connective tissue to form a blood clot.

Description

Technical Field

[0001] Technical Field The present disclosure relates to the field of medical treatment of damaged connective tissues, particularly tendons, ligaments and cartilage.

Background Art

[0002] Background Art Reference materials considered relevant as background to the subject matter disclosed herein are listed below: - WO 2019 / 058373 - WO 2019 / 058375 - US Patent No. 9,180,142 - WO 2001 / 32229 - Markis EA, et al., Nature Reviews. Rheumatology, 23 Sep 2014, 11(1):21 - 34.

[0003] Approval of the above reference materials in this specification should not be construed as meaning that they are relevant in any way to the patentability of the subject matter disclosed herein.

Summary of the Invention

Problems to be Solved by the Invention

[0004] Summary In one aspect, the present disclosure provides a method for treating damaged connective tissue of a subject, or inducing its growth or regeneration, by combining the application of a support matrix with blood collected from the subject and introduced between the support matrix and the damaged portion of the connective tissue to form a blood clot there. Also provided by other aspects of this disclosure are kits, support matrices and conduit systems applicable to the method of the present disclosure.

Means for Solving the Problems

[0005] The term "the aforementioned site" is used to describe the location where whole blood is introduced between the supporting matrix and the damaged area of ​​connective tissue.

[0006] The term “support matrix” is used herein to refer to a matrix applied over a damaged portion of connective tissue, which may be a sheet, film, mesh, wrap or tube made of collagen, a polymer material that may be biodegradable, and may generally be any matrix that can be applied to the damaged portion to help retain introduced whole blood at the site. In some embodiments, the support matrix may be a matrix that is inert to the healing process, while in other embodiments, the matrix may be made of a material that aids the healing process. According to some embodiments of this disclosure, the support matrix is ​​positioned over the damaged portion of connective tissue and is not fastened. In other embodiments, the support matrix is ​​fastened to the tissue by suturing, by surgical staples and / or by other means.

[0007] Blood is introduced to the site in a still fluid state before it has completely coagulated, and the blood clot formed at the site and in physical contact with the damaged area of ​​connective tissue may improve the healing process, such as the regrowth of damaged connective tissue fibers, partial or complete restoration of function, etc.

[0008] Connective tissue can be, for example, tendons, ligaments, or cartilage.

[0009] In one embodiment of the present disclosure, a support matrix is ​​fitted over a damaged area of ​​connective tissue, and blood collected from the subject is introduced at the site, i.e., between the support matrix and the damaged area, using one or more catheters, tubes, or other types of conduits.

[0010] The term “conduit” is used herein to encompass catheters, tubes, or other conduits. The term “conduit system” is used to represent one or more conduits configured for the junctional application of whole blood to the site. A conduit system has a proximal end connectable to an applicator for pushing blood into the conduit system, and a distal end having one or more openings for delivering blood to the site. A conduit system may include a set of such conduits used in the manner disclosed herein. A conduit system typically includes a main portion of a feeder conduit connectable to an applicator, and one or more application conduits. In some embodiments, a conduit system includes one application conduit, which may be a terminal portion of a single conduit including a proximal feeder portion, the terminal portion often having a different and typically narrower diameter than the feeder portion. In other embodiments, a conduit system includes a feeder conduit branching into two or more downstream application conduits for delivering blood to the site, each of which has one or more openings in the terminal portion, through which whole blood is applied to the site.

[0011] The term "applicator" is used herein to refer to a device that can be connected to a feeder conduit, for example, through a Luer-type connector.

[0012] During introduction, the conduit or conduit system may be gradually withdrawn, thereby allowing the space between the supporting matrix and the injured area to be filled with blood to clot. Such introduction during the withdrawal of the conduit system may distribute the blood introduced into the site, resulting in a substantially uniform distribution of blood to clot within the site, particularly over the injured area beneath the supporting matrix, and ultimately a corresponding distribution of blood clots. The introduction of blood to clot into the site and the subsequent withdrawal of the catheter are performed while the blood is still flowable, i.e., before complete coagulation, i.e., before the coagulation process is completed. The coagulation process is then completed while the blood is still in the site.

[0013] The term "blood" is used herein to refer to whole blood, typically venous blood, taken from the subject being treated (interchangeable with "whole blood").

[0014] The term “coagulating blood” is used herein to refer to whole blood that is still flowable and in the process of coagulating. Coagulating blood is typically whole blood mixed with one or more coagulants, one or more anti-anticoagulants (i.e., agents that counteract or inhibit the action of anticoagulants mixed when whole blood is collected from a subject to prevent coagulation), or a combination of one or more coagulants, or one or more anti-anticoagulants.

[0015] The term "blood clot" is used herein to refer to a mass of blood clot formed from introduced, coagulating blood.

[0016] The term "coagulant" is used herein to refer to one or more drugs that induce coagulation, or one or more anticoagulants, i.e., drugs that counteract the action of anticoagulants that may be mixed with collected blood. Therefore, a coagulant may include one or more drugs that induce coagulation, one or more anticoagulants, or a combination thereof.

[0017] In one embodiment, the blood to be coagulated is a mixture of whole blood taken from a subject and one or more coagulants, which is introduced into the subject between the supporting matrix and the connective tissue before the mixture has completely coagulated, i.e., while the blood is still flowable. The coagulation process of the mixture proceeds after injection, and a blood clot is formed between the supporting matrix and the connective tissue.

[0018] Over time, the blood clot may induce the regeneration or growth of damaged connective tissue.

[0019] Thus, in one aspect, the present disclosure provides a method for treating a damaged portion of connective tissue, for example, by inducing the growth of connective tissue fibers throughout the damaged connective tissue portion. The method includes: (a) conforming a support matrix over the portion; (b) positioning the tip of one or more conduits between the portion and the support matrix; and (c) injecting a clotting blood clot from the proximal end of the one or more conduits between the damaged portion of the connective tissue and the support matrix such that the clotting blood clot accumulates between the damaged portion of the connective tissue and the support matrix and subsequently clots.

[0020] In one embodiment, the one or more conduits are retraced during the injection.

[0021] In one embodiment, the clotting blood clot is a mixture of whole blood collected from a subject and one or more clotting agents, and the introduction is performed before complete clotting of the mixture, i.e., when it is still in a flowable state, to enable clotting at the actual site of the blood.

[0022] It should be noted that in any aspect of the present disclosure, whole blood may be collected from a subject and first mixed with an anticoagulant to prevent natural clotting. At a desired time, the whole blood is mixed with one or more clotting agents that induce the clotting process to be completed at the site. The introduction of the clotting blood to the site must be at an appropriate timing such that the blood is still in a flowable state, i.e., before complete clotting.

[0023] In one embodiment, the connective tissue is a tendon, ligament or cartilage. For example, the connective tissue can be the anterior cruciate ligament, or any tendon or cartilage attached to the extremities, such as the shoulder, knee or ankle.

[0024] In one embodiment, the placement is performed in parallel with conforming the support matrix over the damaged area of the connective tissue.

[0025] In one embodiment, one or more conduits are inserted via a minimally invasive incision site using a minimally invasive procedure.

[0026] In one embodiment, the clotting blood clot is introduced into the conduit by an applicator, which may be, for example, a syringe.

[0027] In one embodiment, a conduit system for introducing clotting blood between a support matrix and a damaged connective tissue portion includes a supply tube connectable, for example by a luer-type connector, to an applicator branched into two or more application tubes, the two or more conduits being for introducing the clotting blood to the site.

[0028] In one embodiment, the support matrix is a patch or film, or a tube or wrap capable of enclosing the damaged connective tissue.

[0029] In some embodiments of the method, the support matrix is selected from the group consisting of collagen, polyglycolic acid (PGA), polycaprolactone (PCL), polyvinyl alcohol (PVA), and porcine small intestinal submucosa (SIS).

[0030] In one embodiment, the support matrix is a collagen sheet, film, or wrap.

[0031] In one embodiment, the damaged connective tissue portion includes incised connective tissue fibers.

[0032] In one embodiment, the connective tissue portion includes two incised connective tissue stumps surgically joined or approximated.

[0033] In one embodiment, the joining or approximating includes suturing the two stumps to the support matrix.

[0034] In one embodiment, the introduction is performed such that the clotting blood clot is in close contact with the stump.

[0035] In some embodiments, the method of the present invention further includes passing an oxygen-containing gas through the blood before introducing the blood into the site (for example, to saturate the blood with oxygen). Contact between the blood and the oxygen-containing gas may occur before or after the addition of a coagulant. The oxygen-containing gas may be air or an oxygen-rich gas, such as oxygen-enhanced air or pure oxygen.

[0036] In some embodiments, additional components may be added to the blood. Non-limiting examples include keratin, growth factors, bone marrow, gases, or cells, such as stem cells.

[0037] In some embodiments, the method of the present invention further comprises mixing the blood prior to introduction with one or more autologous cells.

[0038] In another embodiment, the present invention provides a kit for inducing the growth of or regenerating a damaged connective tissue portion of a subject, the kit comprising: (i) one or more blood collection devices for enabling the collection of blood from the subject; (ii) one or more blood collection containers for receiving the blood collected from the subject; (iii) a coagulation assembly configured to enable the mixing of the collected blood with one or more coagulants to initiate a coagulation process of the collected blood; and a conduit system of the above type configured to deliver the blood to be coagulated to the site. The kit may optionally include: (a) an applicator for introducing the blood to be coagulated into the conduit; and (b) instructions for using the kit for inducing the growth of or regenerating a damaged connective tissue portion of a subject.

[0039] In one embodiment, the kit further includes a support matrix.

[0040] In one embodiment, one or more collection containers are vacuum test tubes.

[0041] In one embodiment, the coagulation assembly includes equipment for bringing collected blood into contact with one or more coagulants.

[0042] In one embodiment, the kit further comprises one or more anticoagulants for mixing with collected blood to avoid uncontrolled coagulation.

[0043] In one embodiment, one or more anticoagulants are contained in the one or more blood collection containers.

[0044] In one embodiment, the anticoagulant is selected from the group consisting of ACD-A (anticoagulant citrate-dextrose solution A), EDTA (ethylenediaminetetraacetic acid), EGTA (ethylene glycol tetraacetic acid), citrate, heparin, and oxalate.

[0045] In one embodiment, one or more coagulants or anticoagulants are Ca in the form of a calcium salt such as kaolin, for example, calcium gluconate. 2+ Mg 2+ It is selected from negatively charged phospholipids (PL) and protamine sulfates.

[0046] In one embodiment, one or more conduits are connectable to an applicator at their base end.

[0047] In one embodiment, the kit includes a conduit system for introducing clotting blood to a site, which includes a supply tube that can be connected to an applicator by, for example, a Luer-type connector, extending into two or more application tubes that are conduits for introducing clotting blood to a site between a support matrix and a damaged connective tissue portion.

[0048] In one embodiment, the damaged connective tissue portion to which the kit is used is an incised connective tissue having first and second connective tissue stumps.

[0049] In one embodiment, the kit further includes sutures, surgical staples, or other means for securing the damaged connective tissue portion to a support matrix.

[0050] The connective tissue to which the kit is used may be a ligament, tendon, or cartilage.

[0051] In another embodiment, the Disclosure provides a kit for treating a damaged tissue portion of a subject (for example, for inducing the growth of a damaged connective tissue portion or for regenerating such portion), the kit comprising (i) fitting a support matrix over a damaged area of ​​connective tissue; (ii) positioning the tip of one or more conduits between the damaged area of ​​connective tissue and the support matrix; (iii) collecting whole blood from the subject; (iv) mixing the subject's blood with one or more coagulants or anti-anticoagulation agents; (v) injecting the blood with the coagulants through the proximal end of one or more conduits before complete blood coagulation; and (vi) enabling blood coagulation between the damaged connective tissue and the support matrix (in any applicable order).

[0052] In one embodiment, steps (iii) and (iv) are performed before or concurrently with steps (i) and (ii).

[0053] In several embodiments, the kit can be used in the manner described above.

[0054] Also provided by this disclosure is a support matrix for use in treating damaged connective tissue or in inducing the growth of connective tissue fibers throughout a portion of damaged connective tissue, wherein the treatment comprises binding the matrix to the damaged portion of the connective tissue and introducing coagulating blood between the matrix and the damaged portion.

[0055] The support matrix of the present disclosure may be used in a method comprising (a) fitting the support matrix onto the portion; (b) positioning the tip of one or more conduits between the portion and the support matrix; and (c) injecting a blood clot to coagulate from the proximal end of one or more conduits between the portion and the support matrix (so that the blood clot to coagulate accumulates between the damaged portion of connective tissue and the support matrix and subsequently coagulates).

[0056] The support matrix may be in the form of a patch or film. It may also be in the form of a tube or wrap capable of enclosing the damaged connective tissue portion. The support matrix may be made of collagen sheets, films, or wraps.

[0057] The support matrix of this disclosure may be used in the manner described above.

[0058] Also provided by the present disclosure is a conduit system for use in treating damaged connective tissue or in inducing the growth of connective tissue fibers throughout a portion of damaged connective tissue, wherein the treatment comprises binding the matrix to the damaged portion of the connective tissue and introducing clotting blood into a site between the matrix and the damaged portion; the conduit system is connectable to an applicator at its proximal end and has one or more openings at its tip for introducing clotting blood into the site.

[0059] In one embodiment, the conduit system includes a supply conduit that typically branches into two or more downstream application conduits through a multi-branching element in order to deliver blood to the site.

[0060] In one embodiment, the conduit system is provided in a parts kit that also includes an applicator.

[0061] Embodiment Several embodiments of this disclosure are described herein in the following numbered paragraphs, which are referenced in subsequent paragraphs by reference to those numbers (in a form similar to the claims). These embodiments are added to (and not limit) the disclosure herein. 1. A method for treating a damaged area of ​​connective tissue in a subject (for example, for inducing the growth of connective tissue fibers throughout the damaged area of ​​connective tissue), (a) fitting the support matrix onto the portion; (b) positioning the tip of one or more conduits between the portion and the support matrix; and (c) Injecting a coagulating blood clot from the proximal end of one or more conduits between the damaged portion of connective tissue and the supporting matrix, so that the coagulating blood clot accumulates between the damaged portion and the supporting matrix and subsequently coagulates. Methods that include... 2. The method of Embodiment 1, wherein one or more conduits are retracted during injection. 3. The method of Embodiment 1 or 2, wherein the blood clot to be coagulated is a mixture of whole blood collected from the subject and one or more coagulants, and the introduction is performed before the complete coagulation of the mixture. 4. Any one of embodiments 1 to 3, wherein the connective tissue is a tendon, ligament, or cartilage. 5. Any one of embodiments 1 to 4, wherein the arrangement is carried out in parallel with fitting the support matrix over the damaged area of ​​connective tissue. 6. Any one of embodiments 1 to 5, wherein the conduit is a tube or a catheter. 7. The method of Embodiment 6, wherein one or more conduits are inserted and positioned through a minimal incision site. 8. Any one of Embodiments 1 to 7, wherein the coagulating blood clot is introduced into the conduit by an applicator. 9. The method of Embodiment 8, wherein the applicator is a syringe. 10. Any one of embodiments 1 to 9, wherein the support matrix is ​​a patch mesh, sheet, membrane, or film for placing over or covering a damaged portion of connective tissue. 11. Any one of embodiments 1 to 9, wherein the support matrix is ​​a tube or wrap for placement around a damaged area of ​​connective tissue, for example, around a damaged tendon or ligament. 12. Any one of embodiments 1 to 11, wherein the support matrix is ​​made of collagen. 13. Any one of embodiments 1 to 12, wherein the damaged connective tissue portion includes incised connective tissue fibers. 14. The method of Embodiment 13, wherein the damaged connective tissue portion includes two incised connective tissue stumps that are surgically joined or brought close together. 15. The method of Embodiment 14, wherein the joining or approach includes suturing the two cut ends to the support matrix. 16. The method of embodiment 14 or 15, wherein the introduction is carried out such that the coagulating blood clot comes into contact with the stump. 17. Any one of embodiments 1 to 16, further comprising passing an oxygen-containing gas through the blood. 18. Any one of Embodiments 1 to 17, further comprising mixing the blood prior to introduction with one or more autologous cells. 19. A kit for use in treating a damaged tissue portion of a target (e.g., inducing the growth of a damaged connective tissue portion or regenerating said portion), One or more blood collection devices for collecting blood from the subject; One or more blood collection containers for receiving blood collected from the subject; Apparatus for mixing collected blood with one or more coagulants to initiate blood clotting; One or more conduits (e.g., tubes or catheters) for delivering the blood to clot between the support matrix and the portion, This includes, and in some cases One or more applicators connectable to one or more conduits for introducing coagulating blood into the conduits; optionally Instructions for using a kit to induce growth of or regenerate damaged connective tissue, One or both of the following, A kit that includes this. 20. A kit of embodiment 19, further comprising a support matrix. 21. A kit of Embodiment 20, wherein the support matrix is ​​a patch mesh, sheet, membrane, film, tube, or wrap. 22. A kit of Embodiment 21, wherein the support matrix contains collagen or is made entirely of collagen. 23. Any one of the kits from Embodiments 19 to 22, comprising a conduit system having one or more openings at its tip and being connectable to an applicator at its proximal end, for introducing coagulating blood into the site. 24. The kit of Embodiment 23, wherein the conduit system includes a supply conduit that branches into two or more downstream application conduits for delivering blood to the site. 25. Any one of the kits from Embodiments 21 to 24, comprising an applicator connectable to the conduit system for supplying blood into the conduit system. 26. Any one of the kits from Embodiments 19 to 25, wherein one or more blood collection containers are vacuum test tubes. 27. Any one of the kits from Embodiments 19 to 26, wherein the coagulation assembly includes equipment for bringing collected blood into contact with one or more coagulants. 28. Any one of the kits from Embodiments 19 to 27, further comprising one or more anticoagulants for mixing with collected blood. 29.1 A kit according to Embodiment 28, wherein one or more anticoagulants are contained in one or more blood collection containers. 30. A kit of Embodiment 28 or 29, wherein the anticoagulant is selected from the group consisting of ACD-A (anticoagulant citrate-dextrose solution A), EDTA (ethylenediaminetetraacetic acid), EGTA (ethylene glycol tetraacetic acid), citrate, heparin, and oxalate. 31. Any one of the kits from Embodiments 19 to 30, wherein the one or more coagulants or anticoagulants are selected from kaolin, Ca2+, Mg2+, negatively charged phospholipids (PL), and protamine sulfates. 32. A kit according to any one of embodiments 19 to 31, wherein the damaged connective tissue portion is incised connective tissue having first and second connective tissue stumps. 33. Any one of the kits from Embodiments 19 to 32, further comprising an anchoring element for fixing the damaged connective tissue portion to a support matrix. 34. Any one of the kits from Embodiments 19 to 33, wherein the damaged connective tissue portion is incised connective tissue having first and second connective tissue stumps. 35. A kit according to any one of embodiments 19 to 34, wherein the connective tissue is a ligament, tendon, or cartilage. 36. Any one of the kits from Embodiments 19 to 35 for use in a method for treating, inducing growth of, or regenerating a damaged connective tissue portion, the method being (i) Fitting the support matrix onto the damaged area of ​​connective tissue; (ii) Positioning the tip of one or more conduits between the damaged area of ​​connective tissue and the supporting matrix; (iii) Collect whole blood from the subject; (iv) Mixing the target blood with one or more coagulants; (v) Injecting blood containing a coagulant through the proximal end of one or more conduits before the blood has completely coagulated; and (vi) To enable blood clotting between damaged connective tissue and supporting matrix, Includes. 37. A kit of embodiment 35, wherein steps (iii) and (iv) are performed before or concurrently with steps (i) and (ii). 38. A kit of any one embodiment 19 to 37 for use in a method according to any one of claims 1 to 18. 39. A support matrix for use in treating damaged connective tissue or in inducing the growth of connective tissue fibers throughout a portion of damaged connective tissue, wherein the treatment comprises binding the matrix to the damaged portion of the connective tissue and introducing coagulating blood between the matrix and the damaged portion. 40. Support matrix of embodiment 39, (a) fitting the support matrix onto the portion; (b) positioning the tip of one or more conduits between the portion and the support matrix; and (c) Injecting a coagulating blood clot from the proximal end of one or more conduits between the portion and the supporting matrix (so that the coagulating blood clot accumulates between the damaged portion of connective tissue and the supporting matrix and subsequently coagulates), A support matrix for use in methods including the following. 41. A support matrix of embodiment 40, in which one or more conduits are retracted during injection. 42. A support matrix of Embodiment 40 or 41, wherein the coagulating blood clot is a mixture of whole blood taken from the subject and one or more coagulants, and the introduction is performed before the complete coagulation of the mixture. 43. A support matrix in the form of a patch or film, one of any of embodiments 40 to 42. 44. A support matrix in the form of a tube or wrap, capable of enclosing a damaged portion of connective tissue, as described in any one of embodiments 40 to 42. 45. A support matrix, any one of embodiments 40 to 44, which is a collagen sheet, film, or wrap. 46. ​​A support matrix of any one of embodiments 40 to 45 for use in any one of embodiments 1 to 18. 47. A conduit system for use in treating damaged connective tissue or in inducing the growth of connective tissue fibers throughout a portion of damaged connective tissue, wherein the treatment comprises binding the matrix to the damaged portion of the connective tissue and introducing coagulating blood into a site between the matrix and the damaged portion; the conduit system is connectable to an applicator at its proximal end and has one or more openings at its apical end for introducing coagulating blood into the site. 48. A conduit system of Embodiment 47, comprising a supply conduit branched into two or more downstream application conduits for delivering blood to the site. 49. A conduit system of embodiment 47 or 48, provided in a parts kit that also includes an applicator connectable to the conduit system for supplying blood to the conduit system. 50. A conduit system according to any one of embodiments 47 to 49 for use in any one of embodiments 1 to 18.

[0062] For the purpose of better understanding the subject matter disclosed herein and illustrating how it can be implemented in practice, embodiments are described herein by reference only to non-limiting examples with reference to the accompanying drawings. [Brief explanation of the drawing]

[0063] [Figure 1] Figure 1 is a schematic diagram of an exemplary embodiment of the present disclosure after arthroscopic placement of a regenerative-support matrix to the shoulder tendon. The figure shows a tube inserted through one of the openings formed for the arthroscopic procedure, introducing coagulating blood, and still in place. [Figure 2] Figure 2 is a schematic diagram showing a shoulder tendon (skin removed for illustrative purposes) according to an embodiment of the present disclosure, along with the tip of a tube positioned between the matrix and the tendon. [Figure 3] Figure 3 is a schematic diagram of multiple (three in this example) distal tubes connected to a single multi-branch element. [Figure 4A] Figure 4A is a schematic diagram of an exemplary embodiment of the present disclosure for the treatment of damaged cartilage. [Figure 4B] Figure 4B is a schematic diagram of an exemplary embodiment of the present disclosure for the treatment of damaged cartilage. [Figure 5] Figure 5 is a block diagram of the procedure according to an exemplary embodiment of the present disclosure. [Modes for carrying out the invention]

[0064] Description of specific embodiments Accordingly, aspects of the present disclosure provide a method for regenerating connective tissue in or in a portion of a damaged connective tissue. The method includes fitting a support matrix over the damaged area. The support matrix may be in the form of a patch, or in the form of a hollow element having a lumen that can be wrapped around or enclose the damaged tissue portion, such as a collagen sheet or wrap. The support matrix is ​​for covering or enclosing the damaged connective tissue portion, and the procedure is designed to allow coagulating blood taken from the subject to be introduced into a closed space to form a blood clot over the damaged connective tissue.

[0065] The tip of one or more tubes or catheters is positioned between the damaged area of ​​connective tissue and the supporting matrix to allow the clotting blood to spread evenly within the space. The proximal end of the tube or catheter protrudes outside the body of the subject.

[0066] Referring to Figure 1, it is a schematic diagram showing a portion of the catheter 101, which protrudes (i.e., extends from) the incision site 102 and is temporarily retained in the subject's body after the implantation procedure and before the injection of coagulating blood.

[0067] Referring to Figure 2, it is a schematic diagram showing a portion of the distal section of a catheter 101 in the body of a subject, the tip portion represented by the dashed line 105, which is positioned between a regenerative-support matrix 104, for example, a collagen-based matrix, attached using a surgical anchoring element 106, and a tendon 103. In this exemplary embodiment, the catheter 101 is positioned such that its tip 107 approaches the tip of the support matrix 104. In some embodiments, a tube or catheter having a single distal section 105 is used. In other embodiments, a catheter having multiple distal sections may be used, such as the catheter 110 shown in Figure 3, which has a single proximal section 111 (referred to above as the “feeder conduit”) and multiple distal sections 112 (three in this embodiment, referred to above as the “application conduit”) extending from a multi-branching element 113. One or more distal sections may have a single opening at their end, or, in other embodiments, the ends of the distal sections may each have two or more openings, for example, one end opening and one or more formed in the end wall, to allow for the release of coagulating blood at more than one location along the end. If a distal section has a single opening at its tip, the tip may be positioned below the central portion of the matrix 104, thereby allowing the injected coagulating blood to spread to the peripheral portion below the matrix during injection, or the distal section may be gradually withdrawn during injection, thereby allowing the coagulating blood to spread below the matrix. In other embodiments, it is also possible to use multiple catheters with tips distributed at different locations between the connective tissue and the matrix to ensure sufficient spread of the coagulating blood clot.

[0068] An applicator containing a blood clot to coagulate, such as a syringe, may then be attached to the protruding proximal end of a tube or catheter, and the blood clot to coagulate may then be injected.

[0069] Figures 4A and 4B illustrate exemplary embodiments for treating cartilage damage. The treatment according to this embodiment is an adaptation of the treatment method generally described by Markis EA et al. (Nature Reviews. Rheumatology, 23 Sep 2014, 11(1):21-34), see, for example, Figure 1 of this reference. Generally, cartilage 120 having a full-thickness cartilage-limited lesion 122 is wound cleaned to ensure a healthy and stable margin, and after some further treatment, the lesion is covered with a periosteal flap or collagen membrane 124. A tube 126 is inserted between the membrane and the lesion, and the tube is withdrawn while coagulating whole blood collected from the patient, delivered from an applicator 128 which is a syringe in this specific example, is introduced into the gap 130 between the membrane and the lesion, thereby forming a blood clot 132 at this site, which may assist in the healing process.

[0070] Referring hereto to Figure 5, a block diagram of the procedure according to an exemplary embodiment of the present disclosure, in the first step 140, whole blood is collected from the subject using standard blood collection techniques, typically from venous blood, for example, by using a Vacutainer into which the collected blood is collected. In step 150, the blood is mixed with an anticoagulant, which may be pre-contained in a blood collection container, such as a Vacutainer, as is commonly practiced in the art.

[0071] In step 160, a support matrix, which may be made of collagen, for example, is applied over the damaged area of ​​connective tissue, and the applicator tube of the distal portion of the conduit system, as shown in Figure 3, for example, is positioned between the support matrix and the tissue.

[0072] In step 170, the collected blood is mixed with one or more coagulants or anticoagulants, such as those described above, to initiate whole blood coagulation. Then, in step 180, the syringe is filled with the coagulating blood, and the syringe is connected to a feeder conduit. In some embodiments, the coagulant is contained in the syringe, and as a result, steps 170 and 180 are essentially combined. Next, in step 190, the syringe is operated to push the coagulating blood into the conduit system, introducing the coagulating blood between the support matrix and the tissue. During such introduction, by gradually withdrawing the conduit system, the coagulating blood can be distributed over the injured area and deposited in a substantially uniform manner.

[0073] The order of the steps may be changed. For example, in some embodiments, step 160 may come after step 180.

Claims

1. A kit for use in treating the damaged tissue portion of the target, One or more blood collection devices for collecting blood from the subject; One or more blood collection containers for receiving the blood collected from the subject; Apparatus for mixing the collected blood with one or more coagulants that initiate coagulation of the collected blood; To deliver clotting blood from a blood applicator to a site between the support matrix and the portion, one or more conduits are provided, each connectable to the applicator at its proximal end and having one or more openings at its tip. A kit that includes this.

2. The kit according to claim 1, comprising one or more applicators connectable to one or more conduits for delivering coagulating blood to the conduits.

3. The kit according to claim 2, comprising a support matrix.

4. The kit according to claim 3, wherein the support matrix is ​​a patch mesh, membrane, film, tube, or wrap.

5. The kit according to claim 4, wherein the support matrix is ​​made of collagen.

6. The kit according to claim 5, wherein the conduit system includes one or more conduits, each containing a supply conduit that branches into two or more downstream application conduits for delivering the blood to the site.

7. The kit according to any one of claims 1 to 6, wherein the coagulation assembly includes a device for bringing the collected blood into contact with one or more coagulants.

8. A kit according to any one of claims 1 to 7 for use in a method for treating a damaged connective tissue portion, inducing the growth of the portion, or regenerating the portion, wherein the method is (i) fitting the support matrix onto the damaged area of ​​the connective tissue; (ii) Positioning the tip of one or more conduits between the damaged area of ​​the connective tissue and the support matrix; (iii) Collect whole blood from the subject; (iv) Mixing the blood of the subject with one or more coagulants; (v) Injecting the blood containing the coagulant from the proximal end of one or more conduits before the blood has completely coagulated; and (vi) To enable the coagulation of the blood between the damaged connective tissue and the supporting matrix, A kit that includes this.

9. The kit according to claim 8, wherein steps (iii) and (iv) are performed before or concurrently with steps (i) and (ii).

10. A support matrix for use in treating damaged connective tissue or in inducing the growth of connective tissue fibers throughout a portion of damaged connective tissue, wherein the treatment comprises binding the matrix to the damaged portion of the connective tissue and introducing coagulating blood between the matrix and the damaged portion.

11. A support matrix according to claim 10, (a) fitting the support matrix onto the portion; (b) positioning the tip of one or more conduits between the portion and the support matrix; and (c) Injecting a coagulating blood clot from the proximal end of one or more conduits between the portion and the supporting matrix (so that the coagulating blood clot accumulates between the damaged portion of the connective tissue and the supporting matrix and subsequently coagulates), A support matrix for use in methods including the following.

12. The support matrix according to claim 11, wherein one or more conduits are retraced during injection.

13. The support matrix according to claim 11 or 12, wherein the coagulating blood clot is a mixture of whole blood taken from the subject and one or more coagulating agents, and the introduction is performed before the complete coagulation of the mixture.

14. A support matrix according to any one of claims 11 to 13, in the form of a patch, mesh, membrane, film, tube, or wrap.

15. The support matrix according to claim 14, comprising collagen.

16. A conduit system for use in treating damaged connective tissue or in inducing the growth of connective tissue fibers throughout a portion of damaged connective tissue, wherein the treatment comprises binding the matrix to the damaged portion of the connective tissue and introducing coagulating blood into a site between the matrix and the damaged portion; the conduit system having one or more openings at its tip and connectable at its proximal end to an applicator for introducing coagulating blood into the site.

17. The conduit system according to claim 16, comprising a supply conduit branched into two or more downstream application conduits for delivering the blood to the site.

18. The conduit system according to claim 16 or 17, provided in a parts kit that also includes an applicator connectable to the conduit system for supplying blood to the system.

19. A method for treating damaged connective tissue portions in a subject, (a) fitting the support matrix onto the portion; (b) positioning the tip of one or more conduits between the portion and the support matrix; and (c) Injecting the coagulating blood clot from the proximal end of one or more conduits between the damaged portion of the connective tissue and the supporting matrix so that the coagulating blood clot accumulates between the portion and the supporting matrix and subsequently coagulates. Methods that include...

20. The method according to claim 19, wherein one or more of the conduits are retracted during injection.

21. The method according to claim 19 or 20, wherein the coagulating blood clot is a mixture of whole blood collected from the subject and one or more coagulating agents, and the introduction is performed before the complete coagulation of the mixture.

22. The method according to any one of claims 19 to 21, wherein the connective tissue is a tendon, ligament, or cartilage.

23. The method according to any one of claims 19 to 22, wherein the support matrix is ​​a patch mesh, sheet, membrane, film, tube or wrap.

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