Compressible appendages with a healing-dependent degradation curve

Abstract

The present invention provides a compressible appendage for use with a staple cartridge, the compressible appendage comprising a biocompatible appendage material designed to be releasably retained on the staple cartridge and designed to be delivered to tissue by deployment of staples within the cartridge. The appendage material is formed of a porous polymer matrix and is designed to exhibit a first stiffness that is substantially constant under compression during a first time period from contact with the tissue. The appendage material is further designed to exhibit a second stiffness under compression during a second time period following the first time period. The second stiffness is less than the first stiffness and is designed to decrease over time according to at least one of oxidation, enzymatic hydrolysis, and pH changes caused by interaction with at least one physiological element released from the tissue during the healing process.

Description

Technical Field

[0001] This disclosure relates in general to compressible appendages and methods of using compressible appendages. Background Technology

[0002] Surgical sutures are used in surgical procedures to close openings in tissues, blood vessels, catheters, shunts, or other objects or body parts involved in a particular surgical procedure. These openings can be naturally occurring, such as passages in blood vessels or internal organs similar to the stomach, or they can be created by a surgeon during the surgical procedure, such as by puncturing tissue or blood vessels to create bypasses or anastomoses or by cutting tissue during suturing.

[0003] Most suture devices have a handle with an elongated shaft having a pair of movable, opposing jaws formed at its end for holding and shaping staples between the jaws. The staples are typically housed in a staple cartridge that holds multiple rows of staples and is usually positioned in one of the two jaws for ejecting the staples to the surgical site. During use, the jaws are positioned such that the object to be sutured is positioned between the jaws, and the staples are ejected and shaped when the jaws are closed and the device is actuated. Some suture devices include a blade configured to travel between rows of staples in the staple cartridge to longitudinally cut and / or open sutured tissue between the rows of staples.

[0004] Despite years of improvement, surgical staplers still present several problems. One common issue is leakage that can occur when staples penetrate tissue or other objects in which they are placed, creating a hole. Blood, air, gastrointestinal fluids, and other fluids can leak through the opening formed by the staple, even after the staple is fully formed. The treated tissue can also become inflamed due to the trauma caused by the suture.

[0005] Various implantable materials have been developed for use in conjunction with sutured tissue; however, improved materials are still needed to address some of the aforementioned issues. Summary of the Invention

[0006] Generally, compressible appendages and methods for repairing tissue are provided. In one embodiment, a compressible appendage kit for use with a staple cartridge is provided, and the compressible appendage kit includes a biocompatible appendage material and a pretreatment fluid. The biocompatible appendage material is designed to be releasably held on the staple cartridge and is designed to be delivered to tissue via deployment of staples in the cartridge. The appendage material may be in the form of a porous polymer matrix. The pretreatment fluid is designed to be applied to the appendage material to change the appendage material from an untreated state to a treated state. The appendage material in the untreated state is designed to exhibit a first degradation profile upon delivery to tissue. The appendage material in the treated state is designed to exhibit a second degradation profile different from the first degradation profile upon delivery to tissue.

[0007] The pretreatment fluid may have various configurations. In one embodiment, the pretreatment fluid may be designed to increase the degradation rate of the second degradation curve relative to the first degradation curve. In another embodiment, the pretreatment fluid may be designed to cause the treated appendage to increase the pH adjacent to the appendage upon delivery to a tissue. In other aspects, the pretreatment fluid may be designed to increase the hydrophilicity of the treated appendage. In another embodiment, the pretreatment fluid may be designed to decrease the degradation rate of the second degradation curve relative to the first degradation curve. In another embodiment, the pretreatment fluid may be designed to form a coating deposited on at least a portion of the treated appendage. In another embodiment, the pretreatment fluid may be designed to react with the appendage material to alter the terminal functional groups of at least a portion of the polymer chains forming the porous polymer matrix in the treated state. In other aspects, the pretreatment fluid may be designed to increase the hydrophobicity of the treated appendage compared to the untreated state. In another embodiment, the pretreatment fluid may be designed to form a sealant that seals at least a portion of the pores in the porous polymer matrix. In other aspects, the pretreatment may be designed to terminate at least a portion of a plurality of polymer chains in the porous polymer matrix such that the average length of the plurality of polymer chains in the treated state is less than the average length of the plurality of polymer chains in the untreated state.

[0008] In another embodiment, a surgical method is provided, comprising treating an untreated biocompatible appendage comprising a porous polymer body to produce a treated appendage having a modified degradation profile relative to the untreated appendage. The method further includes releasably holding the treated appendage on a staple cartridge and actuating a surgical suturing device having the staple cartridge and the treated appendage thereon to suture the treated appendage to tissue.

[0009] In one embodiment, treating the biocompatible adjunct material includes immersing the adjunct material in a pretreatment fluid. The altered degradation profile may have a higher degradation rate than that of the untreated adjunct material. In other embodiments, treating the adjunct material causes an increase in the pH adjacent to the treated adjunct material upon delivery to the tissue. In another embodiment, treating the adjunct material increases its hydrophilicity compared to the untreated adjunct material. In yet another embodiment, the altered degradation profile has a lower degradation rate than that of the untreated adjunct material.

[0010] In another embodiment, treating the appendage material involves applying a coating to at least a portion of the appendage material. In another embodiment, treating the appendage material includes applying a pretreatment fluid that reacts with the porous polymer matrix of the appendage material and alters the terminal functional groups of the polymer chains forming the polymer matrix. In another embodiment, treating the appendage material increases the degree of hydrophobicity of the treated appendage material compared to an untreated appendage material. In yet another embodiment, treating the appendage material includes applying a pretreatment fluid that forms a sealant sealing at least a portion of the pores of the porous matrix.

[0011] In another embodiment, treating the accessory material includes applying a pretreatment fluid that terminates at least a portion of the polymer chains of the polymer matrix, such that the average length of the polymer chains of the polymer matrix of the treated accessory material is less than the average length of the polymer chains of the polymer matrix of the untreated accessory material. The degradation rate of the second degradation curve is increased relative to the first degradation curve.

[0012] In another embodiment, a compressible appendage for use with a staple cartridge is provided, the compressible appendage comprising a biocompatible appendage material designed to be releasably retained on the staple cartridge and designed to be delivered to tissue by deployment of staples within the cartridge. The appendage material is formed of a porous polymer matrix and is designed to exhibit a first stiffness that is substantially constant under compression during a first time period from contact with the tissue. The appendage material is further designed to exhibit a second stiffness under compression during a second time period following the first time period. The second stiffness is less than the first stiffness and is designed to decrease over time according to at least one of oxidation, enzymatic hydrolysis, and pH changes caused by interaction with at least one physiological element released from the tissue during the healing process.

[0013] In one embodiment, the appendage is configured to take on the second stiffness in response to oxidation caused by a reaction with the physiological element, which includes a reactive oxygen species. In another embodiment, the appendage is configured to oxidize in response to a reaction with a reactive oxygen species released by mature blood cells or fibroblasts. The reactive oxygen species may include superoxide. In another embodiment, the appendage is configured to oxidize in response to a reaction with a reactive oxygen species released by inflammatory cells. The inflammatory cells may be at least one of leukocytes, neutrophils, basophils, eosinophils, lymphocytes, monocytes, and macrophages. In another embodiment, the reactive oxygen species is at least one of an oxygen-containing enzyme, a free radical, superoxide, and a peroxide. In another embodiment, the reactive oxygen species is O2. - At least one of H2O2, NO and HOCl.

[0014] In another embodiment, the appendage is configured to take the second stiffness in response to enzyme-catalyzed hydrolysis. The enzyme may be lysozyme. In another embodiment, the appendage is configured to take the second stiffness in response to a decrease in pH caused by the presence of the at least one physiological element.

[0015] In other aspects, a suture assembly is provided, comprising a staple cartridge, an anvil, and an appendage. The staple cartridge has a plurality of staples disposed therein, arranged in a staple row and configured to be deployed into tissue. The staple cartridge also includes a blade slot extending through it between the staple rows for receiving a blade to cut tissue along a cutting line. The anvil is positioned opposite the staple cartridge. The appendage is configured to be releasably retained on the staple cartridge or the anvil. The appendage may be in the form of a biocompatible porous polymer material configured to be delivered to tissue from deployment of the staple cartridge by the plurality of staples. The appendage may have a first shape, and at least one first portion of the appendage may be configured to exhibit a first expansion behavior in response to the reception of a unit volume of fluid, and at least one second portion of the appendage may be configured to exhibit a second expansion behavior different from the first expansion behavior in response to the reception of the unit volume of fluid, such that the appendage adopts a second shape different from the first shape. The difference between the first expansion behavior and the second expansion behavior can be designed to apply different pressures to different parts of a tissue having appendages to which they are sutured.

[0016] In one embodiment, a certain amount of expansion of the appendage is designed to provide hemostasis at the cutting line. In another embodiment, a certain amount of expansion of the appendage is designed to seal the hole formed in the tissue by the staples when multiple staples are ejected into the tissue.

[0017] In another embodiment, the at least second portion of the appendage is positioned adjacent to the blade slot, and the at least first portion of the appendage is spaced apart from the blade slot, and the second shape can be designed to apply greater pressure compared to the first shape.

[0018] In another embodiment, the at least one second portion comprises a swellable material different from the biocompatible porous polymer material. The swellable material may include a hydrogel. In another embodiment, the swellable material comprises a porous solid material, and the swellable material is contained in a fluid-soluble capsule in a compressed state. The capsule may be configured to release the swellable material after a predetermined time period following contact with the fluid.

[0019] In another embodiment, the expansion rate of the at least second portion of the appendage in response to the reception of the fluid per unit volume is greater than the expansion rate of the at least first portion of the appendage in response to the reception of the fluid per unit volume.

[0020] In another embodiment, at least one of the plurality of nails includes at least one leg, the at least one leg including a plurality of barbs. When the plurality of nails are ejected into the appendage and tissue, the plurality of barbs are configured to allow the appendage to expand in a first direction and prevent the appendage from retracting in a second direction opposite to the first direction.

[0021] In another embodiment, the at least one second part includes a membrane covering the surface of the appendage.

[0022] In another embodiment, the appendage also includes a color-changing dye that changes color during the expansion of the appendage. The color-changing dye may be a water-chromic ink designed to change color in response to contact with at least one of a fluid and a lipid.

[0023] In another embodiment, an appendage for use with a staple cartridge is provided. The appendage includes a biocompatible appendage configured to be releasably retained on the staple cartridge body and configured to be delivered to tissue via deployment of staples within the cartridge body. The appendage is formed as a porous body comprising a first polymer and a second polymer. The first polymer is designed to degrade according to a first degradation profile that varies according to at least one of hydrolysis in response to interaction with water and heating to physiological temperatures. The second polymer is designed to degrade according to a second degradation profile that varies according to at least one of oxidation, enzymatic hydrolysis, and pH changes caused by interaction with at least one physiological element released from the tissue during the healing process of the tissue.

[0024] In one aspect, the first polymer is designed to swell in response to water absorption and apply a first compressive pressure to the tissue, the first compressive pressure having a magnitude dependent on the first degradation curve, and the second polymer is designed to swell in response to the degradation of the first polymer and apply a second compressive pressure to the tissue, the second compressive pressure having a magnitude dependent on the first degradation curve and the second degradation curve, and the maximum magnitude of the second compressive pressure being less than the maximum magnitude of the first compressive pressure.

[0025] In another embodiment, the first polymer is designed to inhibit the interaction between the second polymer and at least a portion of the at least one physiological element. The first polymer may cover the second polymer.

[0026] In another embodiment, the degradation rate of the first polymer according to the first degradation curve is greater than the degradation rate of the second polymer according to the second degradation curve.

[0027] In another embodiment, the first polymer is a hygroscopic powder or foam.

[0028] In another embodiment, the at least one physiological element includes reactive oxygen species. Reactive oxygen species may include at least one of oxygen-containing enzymes, free radicals, superoxides, and peroxides.

[0029] In another embodiment, the appendage includes a first drug held by the first polymer and designed to be released during the degradation of the first polymer. The first drug may include a hemostatic agent. The appendage may also include a second drug held by the second polymer and designed to be released during the degradation of the second polymer. The second drug may be designed to promote tissue remodeling. In another embodiment, the second drug is designed to be capable of at least one of bolus release and gradual release based on the geometry of the second polymer.

[0030] In one embodiment, a method for treating tissue is provided. The method includes attaching a porous biocompatible appendage to the tissue using one or more staples. The appendage may include a first polymer and a second polymer. The appendage receives at least one of water and heat sufficient to raise the temperature of the appendage to physiological temperature, thereby causing the first polymer to degrade according to a first degradation curve. The appendage receives at least one physiological element released from the tissue during the healing process of the tissue, thereby causing the second polymer to degrade according to a second degradation curve, the second degradation curve varying according to at least one of oxidation, enzymatic hydrolysis, and pH changes caused by interaction with the at least one physiological element.

[0031] In one embodiment, the first polymer expands in response to the reception of water to apply a first compressive pressure to the tissue, the first compressive pressure having a magnitude dependent on the first degradation curve, and the second polymer expands in response to the degradation of the first polymer and applies a second compressive pressure to the tissue, the second compressive pressure having a magnitude dependent at least on the first degradation curve and the second degradation curve. The maximum magnitude of the second compressive pressure is less than the maximum magnitude of the first compressive pressure.

[0032] In another embodiment, the second compression pressure depends on the first degradation curve and the second degradation curve.

[0033] In another embodiment, the first polymer inhibits the interaction between the second polymer and at least a portion of the at least one physiological element. The at least one physiological element may include reactive oxygen species.

[0034] In another embodiment, the first polymer covers the second polymer. In yet another embodiment, the first polymer is at least one of a hygroscopic powder and a foam.

[0035] In another embodiment, the degradation rate of the first polymer according to the first degradation curve is greater than the degradation rate of the second polymer according to the second degradation curve.

[0036] In another embodiment, the appendage further includes a first drug held by the first polymer, the first drug being released during the degradation of the first polymer. The first drug may be a hemostatic agent.

[0037] In another embodiment, the appendage also includes a second drug held by the second polymer, which is released during the degradation of the second polymer. The second drug can promote tissue remodeling.

[0038] In another embodiment, the method further includes at least one of bolus release and gradual release of the second drug based on the geometry of the second polymer. Attached Figure Description

[0039] The invention will be more fully understood from the following detailed description taken in conjunction with the accompanying drawings, in which:

[0040] Figure 1 This is a perspective view of an exemplary embodiment of a conventional surgical suturing and cutting instrument;

[0041] Figure 2 Is with Figure 1 A top view of a staple cartridge used in conjunction with surgical suturing and cutting instruments;

[0042] Figure 3 for Figure 1 A perspective view of the firing pin of a surgical stapler, with an electron beam at its distal end;

[0043] Figure 4 This is a perspective view of another embodiment of the surgical suture device;

[0044] Figure 5 This is a perspective view of yet another implementation of the surgical suture device;

[0045] Figure 6 A longitudinal sectional view of an exemplary embodiment of a staple cartridge having an exemplary appendage attached to the top surface or platform surface of the staple cartridge;

[0046] Figure 7 It is shown Figure 6 A partial schematic diagram of an appendage in an organized deployment state;

[0047] Figure 8 It is a graph showing exemplary degradation curves of the auxiliary material in the untreated state and in the treated state after the application of pretreatment fluid;

[0048] Figure 9 This is a top view schematic diagram of the upper tissue contact surface of an exemplary embodiment of a tissue thickness compensation appendage in an undeformed or pre-deployed state, the tissue thickness compensation appendage being configured to be used for sealing nails along the nail line;

[0049] Figure 10 This shows the state before deformation or deployment. Figure 9 A schematic diagram of the end view of the tissue thickness compensation appendage;

[0050] Figure 11 It shows the deformed or deployed state. Figure 9 A schematic diagram of an end view of a tissue thickness compensation appendage, wherein the expanded portion of the appendage applies sealing pressure to a nail extending through the appendage;

[0051] Figure 12 This is a top view schematic diagram showing an upper tissue contact surface of an appendage configured to apply pressure along a tissue cutting line, in another exemplary embodiment.

[0052] Figure 13 This shows the state before deformation or deployment. Figure 12 A schematic diagram of the end view of the tissue thickness compensation appendage;

[0053] Figure 14 It shows the deformed or deployed state. Figure 13 A schematic diagram of the end view of the tissue thickness compensation appendage;

[0054] Figure 15 This is a schematic diagram showing a side sectional view of a suture assembly in a pre-firing configuration, the suture assembly including an anvil and a staple cartridge, wherein another embodiment of a tissue compensation appendage is mounted on the anvil, the appendage being configured to work in combination with staples fired from the staple cartridge to prevent the appendage from retracting without contacting the tissue after the staples are fired;

[0055] Figure 16 This illustrates the sequence of events immediately following the firing of the staple from the staple cartridge, its passage through the appendages and tissue, and the release of the appendages and tissue from the suture assembly. Figure 15 A schematic diagram of the suture components and accessories;

[0056] Figure 17 This indicates the effects following the absorption of water and / or other physiological fluids from the body. Figure 16 A schematic diagram of the suture components and accessories;

[0057] Figure 18This is a schematic diagram showing a side sectional view of a suture assembly in a pre-firing configuration, the suture assembly including an exemplary embodiment of a composite appendage comprising a first polymer and a second polymer;

[0058] Figure 19 It is shown Figure 18 A schematic diagram of a side sectional view of the composite appendage;

[0059] Figure 20 It is shown Figure 19 A schematic diagram of a side sectional view of a composite appendage attached to the tissue immediately after the firing of the suture assembly;

[0060] Figure 21 It is shown Figure 20 A schematic diagram of an enlarged side sectional view of the composite appendage;

[0061] Figure 22 It is shown Figure 19 A schematic diagram of a side sectional view of a composite appendage attached to the tissue by staples for a predetermined duration after the firing of the suture assembly;

[0062] Figure 23 It is shown Figure 22 A schematic diagram of a side sectional view of the composite appendage;

[0063] Figure 24A It is a graph showing the changes in healing events within the tissue attached to the composite appendage over time;

[0064] Figure 24B It is shown by Figure 19 The curves showing the change in compressive pressure over time between the first and second polymers of the composite appendage applied to the tissue; and

[0065] Figure 24C This shows that they are respectively made by Figure 19 A graph showing the time-varying release rates of the first and second drugs held by the first and second polymers of the composite appendage. Detailed Implementation

[0066] Certain exemplary embodiments will now be described to provide a comprehensive understanding of the principles of the structure, function, manufacture, and use of the apparatuses and methods disclosed herein. One or more examples of these embodiments are illustrated in the accompanying drawings. Those skilled in the art will understand that the apparatuses and methods specifically described herein and illustrated in the drawings are non-limiting exemplary embodiments, and the scope of this disclosure is defined only by the claims. Features shown or described in conjunction with one exemplary embodiment may be combined with features of other embodiments. Such modifications and variations are intended to be included within the scope of the invention.

[0067] Furthermore, in this disclosure, components with similar names in various embodiments generally have similar features; therefore, in specific embodiments, not every feature of every component with a similar name is necessarily fully described. Additionally, the extent to which linear or circular dimensions are used in the description of the disclosed systems, devices, and methods is not intended to limit the types of shapes that can be used in conjunction with such systems, devices, and methods. Those skilled in the art will recognize that equivalent dimensions of such linear and circular dimensions can be readily determined for any geometry. The size and shape of systems and devices and their components may depend at least on the anatomy of the patient in which the system and device will be used, the size and shape of the components with which the system and device will be used, and the method and procedure in which the system and device will be used.

[0068] It should be understood that the terms "proximal" and "distal" are used in this article in relation to the user who grips the instrument handle, such as a clinician. Other spatial terms such as "anterior" and "posterior" similarly correspond to distal and proximal, respectively. It should also be understood that, for convenience and clarity, spatial terms such as "vertical" and "horizontal" are used in the illustrations. However, surgical instruments are used in many orientations and positions, and these spatial terms are not restrictive or absolute.

[0069] Various exemplary devices and methods for performing surgical procedures are provided. In some embodiments, the devices and methods are configured for open surgery, and in other embodiments, they are configured for laparoscopic, endoscopic, and other minimally invasive surgical procedures. These devices can be fired directly by a human user or remotely under the direct control of a robot or similar manipulator. However, those skilled in the art will understand that the various methods and devices disclosed herein can be used in many surgical procedures and applications. Those skilled in the art will further understand that the various instruments disclosed herein can be inserted into the body in any manner, such as through natural orifices, through incisions or perforations formed in tissue, or through an access device (such as a cannula). For example, the working portion or end effector portion of the instrument can be inserted directly into the patient's body or can be inserted through an access device having an end effector of the surgical instrument and a working channel through which an elongated shaft can be advanced.

[0070] It is anticipated that the use of one or more biomaterials and / or synthetic materials (referred to herein as “appendages”) in conjunction with surgical instruments can help improve surgical procedures. “Appendages” are also referred to herein as “appendage materials.” While a variety of different surgical end effectors can benefit from the use of appendages, in some exemplary embodiments, the end effector may be a surgical stapler. When used in conjunction with a surgical stapler, the one or more appendages may be positioned between and / or on the stapler jaws, integrated into a staple cartridge disposed within the jaws, or otherwise placed adjacent to the staple. When the staple is deployed, the one or more appendages can remain at the treatment site with the staple, thereby providing numerous benefits. For example, the one or more appendages can reinforce the tissue at the treatment site, preventing it from being torn or ripped apart by the staple. If the tissue is diseased, healing, and / or undergoing another change in tissue properties, tissue reinforcement may be required to prevent the staple from tearing the tissue. In some cases, appendages can minimize tissue movement (e.g., lung expansion, gastrointestinal distension, etc.) in and around the staple perforation site, which can occur due to tissue deformation that occurs after suturing. Those skilled in the art will recognize that the nail puncture site can act as a stress concentration point, and the size of the hole formed by the nail will increase when the surrounding tissue is under tension. Restricting the movement of the tissue around these puncture sites minimizes the size to which the hole can increase under tension. In some cases, the one or more appendages may be configured to wick or absorb beneficial fluids that further promote healing, such as sealants, blood, glue, etc., and in some cases, the one or more appendages may be configured to degrade to form gels that further promote healing, such as sealants. In some cases, the one or more appendages may be used to help seal the hole formed by the nail when it is implanted in tissue, blood vessels, and various other objects or body parts.

[0071] In other embodiments, the one or more appendages may be used with surgical instruments configured to seal tissue without the use of nails (e.g., by using energy, such as RF or ultrasound), for example, as described in U.S. Patent No. 10,172,611, the entire contents of which are incorporated herein by reference.

[0072] In some cases, the one or more appendages may be configured to compensate for changes in tissue thickness as the appendages are sutured to the tissue. In such cases, the appendage may also be referred to as a "tissue thickness compensator." The tissue thickness compensator has an uncompressed (undeformed) or pre-deployed height that is greater than the height of the staple in its shaped configuration. Additional details regarding exemplary tissue thickness compensators can be found, for example, in U.S. Patent No. 8,864,007, the entire contents of which are incorporated herein by reference. The tissue thickness compensator may be attached to and released from the staple cartridge in a variety of ways, for example, as described in U.S. Patents Nos. 9,272,406 and 10,136,890, each of which is incorporated herein by reference in its entirety.

[0073] In addition to the disclosure herein, further details relating to the one or more of these appendages and other exemplary appendages can be found, for example, in U.S. Patent Nos. 10,172,611 and 10,433,846 and U.S. Patent Application No. 17 / 009,769, filed September 1, 2020, entitled “Compressible Non-Fibrous Adjuncts,” each of which is incorporated herein by reference in its entirety.

[0074] Alternatively or additionally, the one or more appendages may be configured to promote inward tissue growth. In various cases, it is desirable to promote inward tissue growth within the implantable appendage to facilitate the healing of treated tissue (e.g., sutured tissue and / or cut tissue) and / or accelerate patient recovery. More specifically, inward tissue growth within the implantable appendage can reduce the incidence, extent, and / or duration of inflammation at the surgical site. Inward tissue growth within and / or around the implantable appendage can control the spread of infection at the surgical site, for example. Inward growth of blood vessels, particularly leukocytes, within and / or around the implantable appendage can resist infection in and / or surrounding the implantable appendage and adjacent tissues. Inward tissue growth can also facilitate the acceptance of foreign bodies (e.g., implantable appendages and nails) by the patient's body and reduce the likelihood of the patient's body rejecting the foreign body. Rejection of foreign bodies can lead to infection and / or inflammation at the surgical site.

[0075] Alternatively or additionally, one or more agents may be present on and / or therein of the one or more appendages. The one or more agents may vary depending on the desired effect of the one or more agents on the surrounding tissue. As a non-limiting example, the one or more agents may be provided to affect hemostasis, inflammation, macrophages, and / or fibroblasts. Also depending on the desired effect on the tissue, one or more agents may be mixed or combined in any combination, or a single agent may be provided. The one or more agents may be eluted from the one or more appendages in a variety of different ways. As a non-limiting example, the coating on the one or more appendages may be varied to be absorbed at different time points, thereby releasing the one or more agents at different time points; the one or more appendages may be varied to allow the one or more agents to diffuse through the one or more appendages at different rates; the one or more appendages may differ in molecular weight and / or physical properties, thereby causing the one or more agents to be released at different time points; etc. In addition to the disclosure herein, further details regarding drug-eluting appendages can be found in U.S. Patents 9,232,941 and 10,569,071, each of which is incorporated herein by reference in its entirety.

[0076] Surgical suture instruments

[0077] Various surgical instruments can be used in conjunction with one or more appendages and / or one or more agents disclosed herein. Surgical instruments may include surgical staplers. A variety of surgical staplers can be used, such as linear surgical staplers and circular staplers. Typically, linear staplers are configured to produce longitudinal staple sutures and may include elongated jaws having a magazine connected thereto to receive longitudinal staple rows. The elongated jaws may include a blade or other cutting element capable of making incisions between staple rows along tissue held within the jaws. Typically, circular staplers are configured to form annular staple sutures and may include circular jaws having a magazine receiving annular staple rows. Circular jaws may include a blade or other cutting element capable of making incisions within the staple rows to define an opening through tissue held within the jaws. Staplers can be used in a variety of different surgical procedures on a variety of tissues, such as thoracic surgery or gastric surgery.

[0078] Figure 1An example of a linear surgical stapler 10 suitable for use with one or more appendages and / or one or more agents is shown. The stapler 10 typically includes a handle assembly 12, a shaft 14 extending distally from a distal end 12d of the handle assembly 12, and an end effector 30 located at the distal end 14d of the shaft 14. The end effector 30 has opposing lower jaws and upper jaws 32, 34, but other types of end effectors may be used with the shaft 14, the handle assembly 12, and associated components. The lower jaw 32 has a staple channel 56 configured to support a staple cartridge 40, and the upper jaw 34 has an anvil surface 33 facing the lower jaw 32 and configured to operate as an anvil to aid in the deployment of staples from the staple cartridge 40. Figure 1 and Figure 2 (The central nail is obstructed). At least one of the opposing lower jaws and upper jaws 32, 34 is movable relative to the other to clamp tissue and / or other objects disposed therebetween. In some embodiments, at least one of the opposing lower jaws and upper jaws 32, 34 may be fixed or otherwise immovable. In some embodiments, both the opposing lower jaws and upper jaws 32, 34 may be movable. Components of the firing system may be configured to pass through at least a portion of the end effector 30 to eject the nail into the clamped tissue. In various embodiments, a blade 36 or other cutting element may be associated with the firing system to cut tissue during suturing.

[0079] Operation of the end effector 30 can begin with input from a user (e.g., a clinician, surgeon, etc.) at the handle assembly 12. The handle assembly 12 can have many different configurations designed to manipulate and operate the associated end effector 30. In the illustrated example, the handle assembly 12 has a pistol grip housing 18 with various mechanical and / or electronic components disposed therein to operate the instrument 10. For example, the handle assembly 12 may include a knob 26 mounted adjacent to its distal end 12d, which may facilitate rotation of the shaft 14 and / or the end effector 30 about the longitudinal axis L of the shaft 14 relative to the handle assembly 12. The handle assembly 12 may also include a clamping element as part of a clamping system actuated by a clamping trigger 22 and a firing element as part of a firing system actuated by a firing trigger 24. The clamping trigger 22 and the firing trigger 24 may be biased, for example, by a torsion spring to an open position relative to the fixed handle 20. Movement of the clamping trigger 22 toward the fixed handle 20 actuates the clamping system, as described below, which causes the jaws 32, 34 to collapse toward each other and thereby clamp the tissue between them. Movement of the firing trigger 24 actuates the firing system, as described below, which ejects the nail from the nail magazine 40 in which it is disposed and / or advances the blade 36 to cut the tissue trapped between the jaws 32, 34. Those skilled in the art will recognize that various configurations (mechanical, hydraulic, pneumatic, electromechanical, robotic, or other) of the firing system can be used to eject the nail and / or cut the tissue.

[0080] like Figure 2 As shown, the end effector 30 of the illustrated embodiment has a lower jaw 32 that serves as a cartridge assembly or carrier and an opposing upper jaw 34 that serves as an anvil. A staple cartridge 40, containing a plurality of staples, is supported in a staple tray 37, which in turn is supported within a cartridge channel of the lower jaw 32. The upper jaw 34 has a plurality of staple-forming recesses (not shown), each positioned above a corresponding staple from the plurality of staples housed within the staple cartridge 40. Although in the illustrated embodiment, the upper jaw 34 has a proximal pivoting end 34p only on its distal side of engagement with the shaft 14, which is pivotally received within the proximal end 56p of the staple channel 56, the upper jaw 34 can be connected to the lower jaw 32 in various ways. When the upper jaw 34 pivots downward, it moves the anvil surface 33 and causes the staple-forming recesses formed thereon to move toward the opposing staple cartridge 40.

[0081] Various clamping components can be used to open and close the jaws 32 and 34 to selectively clamp tissue between them. As shown, the pivoting end 34p of the upper jaw 34 includes a closing feature structure 34c distal to its pivot attachment to the pin channel 56. Thus, in response to the clamping trigger 22, the closing tube 46 selectively imparts an opening action to the upper jaw 34 during proximal longitudinal movement and a closing action to the upper jaw 34 during distal longitudinal movement, the distal end of which includes a horseshoe-shaped hole 46a engaging the closing feature structure 34c. As described above, in various embodiments, the opening and closing of the end effector 30 can be achieved by the relative movement of the lower jaw 32 relative to the upper jaw 34, the relative movement of the upper jaw 34 relative to the lower jaw 32, or by the movement of both jaws 32 and 34 relative to each other.

[0082] The firing mechanism shown in the specific embodiment includes, for example: Figure 3 The figure shows a firing lever 35 with an electron beam 38 at its distal end. The firing lever 35 is included within a shaft 14, for example, in a longitudinal firing lever slot 14s of the shaft 14, and is guided by a firing action from the shank 12. Actuation of the firing trigger 24 can affect the distal action of the electron beam 38 through at least a portion of the end effector 30, thereby causing the firing of a nail housed in the nail cartridge 40. As shown, a guide 39 protruding from the distal end of the electron beam 38 can engage... Figure 2 The wedge-shaped slider 47 shown in the diagram then pushes the nail driver 48 upward through the nail cavity 41 formed in the nail magazine 40. The upward movement of the nail driver 48 applies an upward force to each of the plurality of nails in the magazine 40, thereby pushing the nail upward against the anvil surface 33 of the upper jaw 34 and producing a shaped nail.

[0083] In addition to firing the nail, the electron beam 38 is also configured to facilitate the closure of jaws 32, 34, the separation of the upper jaw 34 relative to the nail cartridge 40, and / or the cutting of tissue captured between jaws 32, 34. Specifically, a pair of top pins and a pair of bottom pins can engage one or both of the upper and lower jaws 32, 34 to compress jaws 32, 34 toward each other as the firing rod 35 advances through the end effector 30. Simultaneously, a blade 36 extending between the top and bottom pins is configured to cut the tissue captured between jaws 32, 34.

[0084] In use, the surgical stapler 10 can be placed in a cannula or mouth and positioned at the surgical site. The tissue to be cut and sutured can be placed between the jaws 32, 34 of the surgical stapler 10. The characteristic structure of the stapler 10 can be manipulated by the user as needed to achieve the desired position of the jaws 32, 34 at the surgical site and the tissue relative to the jaws 32, 34. After proper positioning has been achieved, the clamping trigger 22 can be pulled toward the fixed handle 20 to actuate the clamping system. The trigger 22 actuates a component of the clamping system, causing the closing tube 46 to be advanced distally through at least a portion of the shaft 14 to cause at least one of the jaws 32, 34 to collapse toward the other to clamp the tissue positioned between them. The trigger 24 can then be pulled toward the fixed handle 20 to actuate a component of the firing system, causing the firing rod 35 and / or the electron beam 38 to be advanced distally through at least a portion of the end effector 30 to fire the staple and optionally sever the tissue trapped between the jaws 32, 34.

[0085] Another example of a surgical instrument in the form of a linear surgical suture device 50 is shown in Figure 4 In the middle. The suture device 50 can usually be used with Figure 1 The suture device 10 is similarly constructed and used. Similar to... Figure 1 The surgical instrument 10, surgical instrument 50 includes a handle assembly 52 having a shaft 54 ​​extending distally from the handle assembly and having an end effector 60 for treating tissue at the distal end of the shaft. The upper and lower jaws 64, 62 of the end effector 60 are configured to capture tissue between them, suture the tissue by firing a pin from a cartridge 66 disposed in the lower jaw 62, and / or create an incision in the tissue. In this specific embodiment, an attachment portion 67 on the proximal end of the shaft 54 ​​is configured to allow the shaft 54 ​​and the end effector 60 to be removably attached to the handle assembly 52. ​​Specifically, a mating feature structure 68 of the attachment portion 67 can mate with a complementary mating feature structure 71 of the handle assembly 52. ​​The mating features structures 68, 71 can be configured to be coupled together via, for example, snap-fit ​​couplings, bayonet couplings, etc., but any number of complementary mating features and any type of coupling can be used to removably attach the shaft 54 ​​to the handle assembly 52. While the entire shaft 54 ​​in the illustrated embodiment is configured to be detachable from the handle assembly 52, in some embodiments, the attachment portion 67 is configured to allow only the distal portion of the shaft 54 ​​to be detached. This detachable connection of the shaft 54 ​​and / or the end effector 60 allows for selective attachment of the desired end effector 60 for a specific procedure, and / or reuse of the handle assembly 52 for multiple different procedures.

[0086] The handle assembly 52 may have one or more features located thereon for manipulating and operating the end effector 60. As a non-limiting example, a knob 72 mounted on the distal end of the handle assembly 52 may facilitate rotation of the shaft 54 ​​and / or the end effector 60 relative to the handle assembly 52. ​​The handle assembly 52 may include a clamping member as part of a clamping system actuated by a movable trigger 74 and a firing member as part of a firing system also actuated by the trigger 74. Thus, in some embodiments, movement of the trigger 74 toward the fixed handle 70 through a first range of motion actuates the clamping member, causing opposing jaws 62, 64 to approach each other to a closed position. In some embodiments, only one of the opposing jaws 62, 64 may move to the closed position. The trigger 74 moves further toward the fixed handle 70 through the second action range to actuate the firing member, causing the nail to be ejected from the nail magazine 66 and / or causing the advance of a knife or other cutting element (not shown) to cut the tissue captured between the jaws 62, 64.

[0087] An example of a surgical instrument in the form of a circular surgical suture device 80 is shown in Figure 5 In the middle. The suture device 80 is typically compatible with... Figure 1 and Figure 4 The linear suture devices 10 and 50 are similarly constructed and used, but some of their features are adapted to their function as circular suture devices. Similar to surgical instruments 10 and 50, surgical instrument 80 includes a handle assembly 82 and a shaft 84 extending distally from the handle assembly, with an end effector 90 for treating tissue at the distal end of the shaft. The end effector 90 may include a cartridge assembly 92 and an anvil 94, each having a tissue contact surface that is substantially circular in shape. The cartridge assembly 92 and anvil 94 may be coupled together via a shaft 98 extending from the anvil 94 to the handle assembly 82 of the suture device 80, and an actuator 85 on the handle assembly 82 may retract and advance the shaft 98 to move the anvil 94 relative to the cartridge assembly 92. The anvil 94 and cartridge assembly 92 can perform various functions and can be configured to capture tissue between them, suture tissue by firing staples from a cartridge 96 of the cartridge assembly 92, and / or create incisions in the tissue. Generally speaking, the chamber assembly 92 can accommodate a chamber containing nails, and the nails can be deployed against the anvil 94 to form a circular nail pattern, such as nails surrounding the periphery of a tubular main organ.

[0088] In one embodiment, shaft 98 may be formed of a first portion and a second portion (not shown) configured to be releasably coupled together to allow disengagement of the anvil 94 from the storage chamber assembly 92, allowing greater flexibility in positioning the anvil 94 and storage chamber assembly 92 within the patient's body. For example, the first portion of shaft may be disposed within the storage chamber assembly 92 and extend distally beyond it, terminating in a distal mating feature. The second portion of shaft may be disposed within the anvil 94 and extend proximally beyond it, terminating in a proximal mating feature. In use, the proximal and distal mating features may be coupled together to allow movement of the anvil 94 and storage chamber assembly 92 relative to each other.

[0089] The shank assembly 82 of the stapler 80 may have various actuators disposed thereon capable of controlling the movement of the stapler. For example, the shank assembly 82 may have a knob 86 disposed thereon for positioning the end effector 90 by rotation, and / or a trigger 85 for actuating the end effector 90. Movement of the trigger 85 toward the fixed shank 87 through a first range of motion may actuate a component of the clamping system toward the jaws, for example, moving the anvil 94 toward the cartridge assembly 92. Movement of the trigger 85 toward the fixed shank 87 through a second range of motion may actuate a component of the firing system to deploy a staple from the cartridge assembly 92 and / or advance the blade to cut tissue captured between the cartridge assembly 92 and the anvil 94.

[0090] The illustrated examples of surgical suturing instruments 10, 50, and 80 are merely a few examples of many different configurations and associated methods of use that can be used in conjunction with the disclosure provided herein. While the illustrated examples are all configured for use in minimally invasive surgery, it should be understood that instruments configured for use in open surgery, such as the open linear suture device described in U.S. Patent No. 8,317,070, filed February 28, 2007, entitled “Surgical Stapling Devices That Produce Formed Staples Having Different Lengths,” can be used in conjunction with the disclosure provided herein. Further details of the examples shown, as well as additional examples of surgical suture devices, their components, and related methods of use, are provided in the following patents: U.S. Patent Publication No. 2013 / 0256377, filed February 8, 2013, entitled “Layer Comprising Deployable Attachment Members”; U.S. Patent No. 8,393,514, filed September 30, 2010, entitled “Selectively Orientable Implantable Fastener Cartridge”; U.S. Patent No. 8,317,070, filed February 28, 2007, entitled “Surgical Stapling Devices That Produce Formed Staples Having Different Lengths”; and U.S. Patent No. 7,143, filed June 21, 2005, entitled “Surgical Instrument Incorporating EAP Blocking Lockout Mechanism”.U.S. Patent No. 925, filed November 8, 2013, entitled "Sealing Materials For Use in Surgical Stapling"; U.S. Patent No. 2015 / 0134077, filed November 8, 2013, entitled "Sealing Materials for Use in Surgical Procedures"; U.S. Patent No. 2015 / 0134076, filed November 8, 2013, entitled "Hybrid Adjunct Materials for Use in Surgical Stapling"; U.S. Patent No. 2015 / 0133996, filed November 8, 2013, entitled "Positively Charged Implantable Materials and Method of Forming the Same"; and U.S. Patent No. 2015 / 0133996, filed November 8, 2013, entitled "Tissue Ingrowth Materials and Method of Using the U.S. Patent Publication No. 2015 / 0129634 entitled "Same", U.S. Patent Publication No. 2015 / 0133995 entitled "Hybrid Adjunct Materials for Use in Surgical Stapling" filed November 8, 2013, U.S. Patent Application No. 14 / 226,142 entitled "Surgical Instrument Comprising a Sensor System" filed March 26, 2014, and U.S. Patent Application No. 14 / 300,954 entitled "Adjunct Materials and Methods of Using Same in Surgical Methods for Tissue Sealing" filed June 10, 2014, are all incorporated herein by reference in their entirety.

[0091] Implantable appendages

[0092] As noted above, various implantable appendages are provided for use in conjunction with surgical suture instruments. When used in conjunction with a surgical suture device, one or more of these appendages may be positioned between and / or on the jaws of the suture device, integrated into a staple cartridge disposed within the jaws, or otherwise placed adjacent to the staples. For example, as... Figure 6 As shown, the accessory 104 is positioned against the staple cartridge 102. For simplicity, the accessory 104 is typically located... Figure 6 The various structural configurations of the appendages are shown below, and are described in more detail below. Although in Figure 6 The center is partially obscured, but the staple cartridge 102 includes staples 106 configured to be deployed into tissue. Staples 106 may have any suitable unformed (pre-deployed) height. For example, staples 106 may have an unformed height between approximately 2 mm and 4.8 mm. Prior to deployment, the crown of the staple may be supported by a staple driver (not shown).

[0093] In the illustrated embodiments, the appendage 104 may releasably engage with at least a portion of the top surface or platform surface 108 of the staple cartridge 102. In some embodiments, the top surface 108 of the staple cartridge 102 may include one or more surface feature structures. Alternatively or additionally, one or more adhesives may be used to releasably engage the appendage with the staple cartridge 102. The one or more surface feature structures and / or the one or more adhesives may be configured to engage the appendage 104 to prevent undesired movement of the appendage 104 relative to the staple cartridge 102 and / or to prevent premature release of the appendage 104 from the staple cartridge 102. Exemplary surface feature portions are described in U.S. Patent Publication 2016 / 0106427, the entire contents of which are incorporated herein by reference. Additional details regarding adhesives and other exemplary adhesives for temporary attachment to devices can be found in U.S. Patents 9,282,962, 10,172,617, 10,172,618, 10,258,332, 10,517,592, 10,548,593, 10,568,621, and 10,588,623, each of which is incorporated herein by reference in its entirety. Additional details regarding attachment methods and other exemplary methods can be found in U.S. Patents 10,166,023 and 10,349,939 and U.S. Patent Application 17 / 022,520, filed September 16, 2020, entitled “Method of Applying Buttress to End Effector of Surgical Stapler,” each of which is incorporated herein by reference in its entirety.

[0094] In some cases, the appendage can be compressible to allow it to compress to different heights, thereby compensating for varying tissue thicknesses trapped within the deployed nail. For example, as... Figure 6 As shown, the appendage 104 has an uncompressed (undeformed) or pre-deployed height and is configured to deform to one of a plurality of compressed (deformed) or deployment heights. Therefore, the appendage 104 may have a firing height greater than that of the nail 106 disposed within the nail magazine 102 (e.g., Figure 7The uncompressed height (H) of the firing pin 106a. That is, the appendage 104 may have an undeformed state in which the maximum height of the appendage 104 is greater than the maximum height of the firing pin (e.g., a pin in a shaped configuration). In such cases, the appendage may be referred to as a "tissue thickness compensation member". In one embodiment, the uncompressed height of the appendage 104 may be about 10%, about 20%, about 30%, about 40%, about 50%, about 60%, about 70%, about 80%, about 90%, or about 100% higher than the firing height of the pin 106. In some embodiments, for example, the uncompressed height of the appendage 104 may be more than 100% higher than the firing height of the pin 106.

[0095] The appendage can have various configurations and can be formed from a variety of materials. Typically, the appendage can be formed from one or more of the following: membranes, foams, injection-molded thermoplastics, vacuum thermoforming materials, fibrous structures, additive manufacturing materials, and mixtures thereof. The appendage may also include one or more bio-derived materials and one or more pharmaceuticals. Each of these materials is discussed in more detail below.

[0096] The appendages can be formed from foams, such as closed-cell foams, open-cell foams, or sponges. An example of how such appendages can be manufactured is from animal-derived collagen (such as porcine tendons), which can then be processed and freeze-dried into a foam structure. Examples of various foam appendages are further described in the previously mentioned U.S. Patent No. 8,393,514, entitled “Selectively Orientable Implantable Fastener Cartridge,” filed September 30, 2010, the entire contents of which are incorporated herein by reference.

[0097] The appendage may also be formed from a membrane of any suitable material or combination thereof discussed below. The membrane may comprise one or more layers, each layer having a different degradation rate. Furthermore, the membrane may have various regions formed therein, for example, reservoirs capable of releasably retaining one or more different forms of a pharmaceutical agent. One or more different coatings may be used to seal the reservoir containing at least one pharmaceutical agent; these coatings may comprise absorbable or non-absorbable polymers. The membrane may be formed in various ways, for example, it may be an extruded molding membrane or a compression molding membrane.

[0098] The appendage may also be formed from injection-molded thermoplastic or vacuum-formed materials. Examples of various molded appendages are further described in U.S. Patent Publication 2013 / 0221065, filed February 8, 2013, entitled “Fastener Cartridge Comprising A Releasably Attached Tissue Thickness Compensator,” the entire contents of which are incorporated herein by reference. The appendage may also be a fiber-based lattice, which may be woven, knitted, or nonwoven, such as a loosely woven fabric constructed by meltblowing, needle punching, or thermal bonding. The appendage may have multiple regions that can be formed from lattices of the same type or different types, which can be combined to form the appendage in a variety of different ways. For example, fibers may be woven, braided, knitted, or otherwise interconnected to form regular or irregular structures. Fibers may be interconnected such that the resulting appendage is relatively loose. Alternatively, the appendage may comprise tightly interconnected fibers. The appendage may be in the form of a sheet, tube, spiral, or any other structure that may include flexible portions and / or more rigid reinforcing portions. Appendages can be configured to allow for denser fibers in certain areas and lower-density fibers in other areas. Depending on the intended application of the appendage, the fiber density can vary in different directions along one or more dimensions of the appendage.

[0099] In other embodiments, the appendages may be formed using a 3D printing process compatible with the absorbable polymer. Non-limiting examples of suitable 3D printing processes include stereolithography (SLA or SL), material jetting, selective laser sintering (SLS), and filament fabrication as understood by those skilled in the art.

[0100] The appendages can also be hybrid constructs, such as laminated composites or melt-interlocked fibers. Examples of various hybrid constructs are further described in the following patents: U.S. Patent Publication 2013 / 0146643, filed February 8, 2013, entitled "Adhesive FilmLaminate," and U.S. Patent Publication 7,601,118, filed September 12, 2007, entitled "Minimally Invasive Medical Implant And Insertion Device And Method For Using The Same," the entire contents of which are incorporated herein by reference.

[0101] Material

[0102] The appendages according to the technology can be formed from a variety of materials. These materials can be used in various embodiments for different purposes. These materials can be selected according to the desired treatment to be delivered to the tissue in order to facilitate tissue ingrowth. The materials described below can be used to form appendages in any desired combination.

[0103] These materials may include bioabsorbable polymers and biocompatible polymers, including homopolymers and copolymers. Non-limiting examples of homopolymers and copolymers include p-dioxane (PDO or PDS), polyglycolic acid (PGA) (e.g., Dexon and Neoveil), poly(lactic-co-glycolic acid copolymer) (PLGA), polycaprolactone (PCL), polyglycolic acid (PGL), trimethylene carbonate (TMC), polylactic acid (PLA) (e.g., Linvatec Bioscrew and Bionx Implants SmartScrew), poly(trimethylene carbonate) (PTMC), polyethylene diglycolate (PEDG), poly(propylene fumarate) (PPF), polyvinyl ether (PEE), poly(ethylene glycol) (PEG), poly(N-isopropylacrylamide), poly(amino acids), poly(epoxy carbonate), poly(propylene 2-oxide carbonate), poly(diol citrate), polymethacrylate anhydride, poly(ethoxyethylene diglycolate), poly(glycolic acid-lactic acid copolymer) (PLA / PGA) (e.g., for Vicryl, Vicryl PLA / PGA materials from Rapide, PolySorb, and Biofix, polyurethanes (such as Elastane, Biospan, Tecoflex, Bionate, and Pellethane fibers), polyorthoesters, polyanhydrides (e.g., Gliadel and Biodel polymers), polyoxyesters, polyesteramides (e.g., REVA ReZolve scaffolds), and tyrosine-based polyesteramides (e.g., TYRX). Copolymers may also include poly(lactic acid-polycaprolactone copolymer) (PLA / PCL) (e.g., hydrolyzed for 16-18 months), poly(L-lactic acid-polycaprolactone copolymer) (PLLA / PCL), poly(glycolic acid-trimethylene carbonate copolymer) (PGA / TMC) (e.g., Maxon), poly(glycolic acid-caprolactone copolymer) (PCL / PGA) (e.g., Monocryl and Capgly), PDS / PGA / TMC (e.g., Biosyn), PDS / PLA, PGA / PCL / TMC / PLA (e.g., Caprosyn), LPLA / DLPLA (e.g., Optima), PLGA-PCL (e.g., 15:85 (PCL: 50% D,L-lactide: 50% glycolide), 40:60 (PCL: 50% D,L-lactide: 50% glycolide), and 40:60 (PCL: 85%). D,L-lactide (15% glycolide), PLGA-PCL-PLGA and PLGA-PEG-PLGA.

[0104] The appendages may also include specialty polymer end groups, including (meth)acrylates and organically derived polymers. Non-limiting examples of organically derived polymers include those derived from collagen (e.g., Avitene, Endoavitene, Instat, Integran, Veritas, and microfibrillary collagen (MFC)).

[0105] The appendages may also include active agents, such as viable cell cultures (e.g., excised autologous tissue, reagents for stem cell therapy (e.g., Biosutures and Cellerix SL), hemostatic agents, and tissue healing agents). Non-limiting examples of hemostatic agents may include cellulose such as oxidized regenerated cellulose (ORC) (e.g., Surgicel and Interceed), fibrin / thrombin (e.g., Thrombin-JMI, TachoSil, Tiseel, Floseal, Evicel, TachoComb, Vivostat, and Everest), autologous platelet plasma, gelatin (e.g., Gelfilm and Gelfoam), hyaluronic acid such as microfibers (e.g., yarns and textile fabrics) or other hyaluronic acid-based structures or hyaluronic acid-based hydrogels. Hemostatic agents may also include polymeric sealants, such as, for example, bovine serum albumin and glutaraldehyde, human serum albumin and polyethylene crosslinking agents, and ethylene glycol and trimethylene carbonate. Polymer sealants may include FocalSeal surgical sealant developed by Focal Inc.

[0106] The appendages described herein are capable of releasably retaining at least one pharmaceutical agent, selectable from a large number of different agents. The agents include, but are not limited to, drugs or other agents having the desired function contained within or associated with the appendages. The agents include, but are not limited to, antimicrobial agents (such as antibacterial agents and antibiotics), antifungal agents, antiviral agents, anti-inflammatory agents, growth factors, analgesics, anesthetics, tissue matrix degradation inhibitors, anticancer agents, hemostatic agents, and other agents that induce biological responses.

[0107] Non-limiting examples of antimicrobial agents include ionic silver, aminoglycosides, streptomycin, polypeptides, bacitracin, triclosan, tetracycline, doxycycline, minocycline, demeclocycline, tetracycline, oxytetracycline, chloramphenicol, nitrofurans, furazolidone, nitrofurantoin, β-lactams, penicillin, amoxicillin, amoxicillin + clavulanic acid, azlocillin, flucloxacillin, ticarcillin, piperacillin + tazobactam, tebuconazole, and Biopiper. TZ, Piperacillin, Carbapenems, Imipenem, Meropenem, Ertapenem, Donipenem, Biapenem, Panipenem / Betamilon, Quinolones, Ciprofloxacin, Enoxacin, Gatifloxacin, Gemimifloxacin, Levofloxacin, Lomefloxacin, Moxifloxacin, Naproxic Acid, Norfloxacin, Sulfonamides, Sulfamiron, Sulfaacetyl, Sulfadiazine, Silver Sulfadiazine, Sulfamethazine, Sulfamethazine, Sulfamethoxazole, Sulfasylpyridinium, Sulfamethoxazole, Compound Sulfamethoxazole, Prontocillin, Lodosin, Geldermycin, Atrazine, Fidamycin, Glycopeptides Teicoplanin, vancomycin, tervanomycin, dabazomycin, orivoxil, lincosamides, clomacromycin, lincomycin, lipopeptides, dapoxetine, macrolides, azithromycin, clarithromycin, erythromycin, roxithromycin, tebuconazole, spiramycin, oxazolidinone, linezolid, aminoglycosides, amikacin, gentamicin, kanamycin, neomycin, netilmicin, tobramycin, paromomycin, cephalosporins, cefbiprexa, cefoloza, cefixime, fluoxetine, monoclonal cyclophosphamide, aztreonam, colistin, and polymyxin B.

[0108] Non-limiting examples of antifungal agents include triclosan, polyene, amphotericin B, candidiasis, ferulic acid, haramicin, natamycin, nystatin, sclerotinib, azoles, imidazoles, triazoles, thiazoles, allylamine, amorolfine, butenafine, naftifine, terbinafine, echinococcins, anisoflurane, caspoflurane, miafungin, ciclopirox olamine, and benzoic acid.

[0109] Non-limiting examples of antiviral agents include: uncoated inhibitors, such as, for example, amantadine, rimantadine, and pleconaril; reverse transcriptase inhibitors, such as, for example, acyclovir, lamivudine, antisense, fomivirsen, morpholino compounds, ribosylase, and rifampin; and virucidal agents, such as, for example, cyanovirin-N, griffithsin, scytovirin, α-lauroyl-L-arginine ethyl ester (LAE), and ionic silver.

[0110] Non-limiting examples of anti-inflammatory agents include nonsteroidal anti-inflammatory agents (e.g., salicylates, aspirin, diflunisal, propionic acid derivatives, ibuprofen, naproxen, fenolofen, and cloxoprofen), acetic acid derivatives (e.g., tometidine, sulindac, diclofenac sodium), enolic acid derivatives (e.g., piroxicam, meloxicam, doxicoxicam, and lornoxicam), anthranilic acid derivatives (e.g., mefenamic acid, meclofenamic acid, and flufenamic acid), selective COX-2 inhibitors (e.g., celecoxib (Celebrex), parecoxib, rofecoxib (Vox), sulfonylureas, nimesulide, and clotrimazole), immunoselective anti-inflammatory derivatives, corticosteroids (e.g., dexamethasone), and iNOS inhibitors.

[0111] Non-limiting examples of growth factors include cellular signaling molecules that stimulate cell growth, healing, remodeling, proliferation, and differentiation. Exemplary growth factors can be short-range (paracrine), long-range (endocrine), or autostimulatory (autocrine). Further examples of growth factors include growth hormones (e.g., recombinant growth factor, Nutropin, Humatrope, Genotropin, Norditropin, serotonin, omeprazole, and biosynthetic growth factors), epidermal growth factor (EGF) (e.g., inhibitors, gefitinib, erlotinib, afatinib, and cetuximab), heparin-bound EGF-like growth factors (e.g., epidermal regulatory factors, β-cytokinin, bimodalin, and Epigen protein), transforming growth factor α (TGF-α), neuromodulators 1-4, fibroblast growth factor (FGF), etc. FGFs (e.g., FGF1-2, FGF2, FGF11-14, FGF18, FGF15 / 19, FGF21, FGF23, FGF7 or keratinocyte growth factor (KGF), FGF10 or KGF2 and phenytoin), insulin-like growth factor (IGFs) (e.g., IGF-1, IGF-2 and platelet-derived growth factor (PDGF)), vascular endothelial growth factor (VEGFs) (e.g., inhibitors, bevacizumab, ranibizumab, VEGF-A, VEGF-B, VEGF-C, VEGF-D and becapprenomy).

[0112] Additional non-limiting examples of growth factors include cytokines such as granulocyte-macrophage colony-stimulating factor (GM-CSF) (e.g., inhibitors that suppress inflammatory responses and GM-CSF manufactured using recombinant DNA technology and via recombinant yeast-derived sources), granulocyte colony-stimulating factor (G-CSF) (e.g., filgrastim, levofloxacin, and eubrazol), tissue growth factor β (TGF-B), leptin, and interleukins (ILs) (e.g., IL-1a, IL-1b, konnabidiol, IL-2, adelin, interking, dentine, IL-3, IL-6, IL-8, IL-10, IL-11, and olprespin). Non-limiting examples of growth factors also include erythropoietin (e.g., dabepoetin, epcept, dynepo, epmax, neorecormon, silapo, and retacrit).

[0113] Non-restrictive examples of analgesics include anesthetics, opioids, morphine, codeine, oxycodone, hydrocodone, buprenorphine, tramadol, non-anesthetics, acetaminophen, paracetamol, nonsteroidal anti-inflammatory drugs, and flupirtine.

[0114] Non-limiting examples of anesthetics include local anesthetics (e.g., lidocaine, benzocaine, and ropivacaine) and general anesthetics.

[0115] Non-limiting examples of tissue matrix degeneration inhibitors that inhibit the action of metalloproteinases (MMPs) and other proteases include MMP inhibitors (e.g., exogenous MMP inhibitors, hydroxamic acid-based MMP inhibitors, barmasta (BB-94), ilomastasta (GM6001), marimastasta (BB2516), thiols, periodat (doxycycline), squaric acid, BB-1101, hydroxyurea, hydrazine, endogenous carbamoyl phosphate, β-lactams, and tissue inhibitors of MMPs (TIMPs)).

[0116] Non-limiting examples of anticancer agents include monoclonal antibodies, bevacizumab (Avastin), cell / chemical inducers, alkylating agents (e.g., bifunctional, cyclophosphamide, dichloromethyldiethylamine, chlorambucil, melphalan, monofunctional, nitrosourea, and temozolomide), anthracyclines (e.g., doxorubicin, epirubicin, idarubicin, mitoxantrone, and pentorubicin), cytoskeleton disruptors (e.g., paclitaxel and docetaxel), epothilone agents that limit cell division by inhibiting microtubule function, inhibitors of various enzymes required to block cell division or certain cellular functions, histone deacetylase inhibitors (e.g., vorinostat and romidesin), and topoisomers. Enzyme I inhibitors (e.g., irinotecan and topotecan), topoisomerase II inhibitors (e.g., etoposide, teniposide, and tafluposide), kinase inhibitors (e.g., bortezomib, erlotinib, gefitinib, imatinib, vemurafenib, and vemodigine), nucleotide analogs (e.g., azacitidine, azathioprine, capecitabine, cytarabine, deoxyfluorouridine, fluorouracil, 5-FU, Adrucil, Carac, Efudix, Efudex, Fluoroplex, gemcitabine, hydroxyurea, mercaptopurine, and thioguanine), and peptide antibiotics that cleave DNA and disrupt DNA unwinding / entanglement (e.g., bortezomib, erlotinib, gefitinib, imatinib, vemurafen ... Platinum-based antitumor agents that inhibit DNA repair and / or synthesis of cross-linked DNA (e.g., carboplatin, cisplatin, oxaliplatin, and eloxatin), retinoids (e.g., retinoic acid, retinoic acid, and besalodin), vinblastines that inhibit mitosis and microtubule formation (e.g., vincristine, vinorelbine, vinorelbine, vinorelbine), and angiogenesis inhibitors that inhibit cell growth or cell expansion (e.g., axitinib (Inritar), bevacizumab (Avastin), cabozantinib (Cometriq), everolimus (Afinil, Zortress), lenalidomide (Lepril), pazopanib (Vitrant), and remoxicillin). Rucizumab (Cyramza), Regorafenib (Stivarga), Sorafenib (Nexavar), Sunitinib (Sutent), Thalidomide (Cilavir, Sesylvaline), Vandertanib (Caprelsa), Zib-Aflibercept (Zaltrapezil), Anti-angiogenic polysaccharides, Alpradine (Dehydrometasine B), Saponins (20(S)-Protopanaxadiol and 20(S)-Protopanaxtriol), Anti-intestinal obstruction agents, Prokinetic agents, Immunosuppressants (e.g., Tacrolimus), Blood modulators (e.g., Vasodilators, Viagra and Nifedipine), 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitors (e.g., Atorvastatin), and Anti-angiogenic agents.

[0117] Exemplary agents also include agents that passively promote wound healing, such as nutrients, oxygen-removing agents, amino acids, collagen-synthesizing agents, glutamine, insulin, butyrate, and dextran. Exemplary agents also include anti-adhesion agents, non-limiting examples of which include hyaluronic acid / carboxymethyl cellulose (seprafilm), oxidized regenerated cellulose (Interceed), and 4% icodextrin (Extraneal, Adept).

[0118] Exemplary agents also include those that promote coronary artery disease (CAD) (e.g., VEGF). 165 Protein, AdVEGF 165 ,AdVEGF 121 and VEGF 165 Plasmids) or peripheral artery disease (PAD) (e.g., VEGF) 165 plasmids, AdVEGF 121 SB-509 (SFP-VEGF plasmid), AdVEGF 165 A blood supply regeneration agent following Ad2-HIF1α-VP16 (WALK trial).

[0119] Drug release

[0120] The appendage according to the technology can be associated with at least one agent in a variety of different ways to provide a desired effect, such as promoting inward growth of tissue. The at least one agent can be designed to be released from the appendage in a variety of spatial and temporal patterns to trigger a desired healing process at the treatment site. The agent can be disposed in, combined with, incorporated into, dispersed within, or otherwise associated with the appendage. For example, the appendage may have one or more regions that releasably hold one or more different agents. These regions can be different reservoirs of various sizes and shapes that hold agents in various ways, or other different or continuous regions within the appendage. In some aspects, a particular configuration of the appendage allows it to releasably hold one or more different agents.

[0121] Regardless of how the drug is disposed within the appendage, an effective amount of at least one drug can be encapsulated in a container, such as a microcapsule, a pellet in the form of microbeads, or any other container. The container may be formed from a bioabsorbable polymer.

[0122] Targeted delivery and release of at least one agent from an appendage can be accomplished in a variety of ways depending on various factors. Typically, the at least one agent can be released from the appendage material as a bolus dose, such that the agent is released substantially immediately upon delivery of the appendage material to the tissue. Alternatively, the at least one agent can be released from the appendage over a period of time, which can be minutes, hours, days, or longer. The rate of timed release and the dose of drug released can depend on various factors, such as the degradation rate of the area where the agent is released, the degradation rate of one or more coatings or other structures used to retain the agent in the appendage, environmental conditions at the treatment site, and various other factors. In some aspects, when the appendage has more than one agent disposed therein, the bolus dose release of the first agent can modulate the release of a second agent that begins to be released after the release of the first agent. The appendage may include multiple agents, each of which can influence the release of one or more other agents in any suitable manner.

[0123] The release of at least one agent, as a bolus dose or a timed release, may occur or begin substantially immediately after the adjuvant material is delivered to the tissue, or may be delayed for a predetermined time. The delay may depend on the structure and properties of the adjuvant or one or more regions thereof.

[0124] The adjuvant material can be designed to facilitate the dispensing of an effective amount of one or more agents carried within the adjuvant to provide the desired effect. For example, targeted delivery of the agent can be achieved by incorporating the agent into a patterned region within the adjuvant (e.g., a reservoir such as a hole or other structure), the pattern allowing the agent to form a spatial distribution during delivery. The agent disposed within the reservoir can be incorporated into different containers. The reservoir may include more than one type of different agent. The one or more agents can be eluted from the adjuvant in a homogeneous or non-homogeneous spatial and / or temporal manner to deliver the desired treatment. The structure of the adjuvant and the manner in which the agent is released from it can be used to influence or control tissue regeneration. Furthermore, tissue regeneration can be promoted at certain locations at the treatment site, while not at other locations.

[0125] Implantable appendages with adjustable degradation profiles

[0126] As discussed above, the implementation of an appendage can serve a variety of functions, such as enhancing tissue at the treatment site, minimizing tissue movement in and around the pin insertion site, and compensating for tissue thickness. This functionality relies on one or more mechanical properties of the appendage, such as strength (e.g., compressive strength, tensile strength), elastic modulus / stiffness, etc., which remain at or above a predetermined level after implantation to ensure the appendage's functionality. However, after implantation, the appendage can absorb bodily fluids (e.g., water and / or aqueous fluids). These fluids can chemically react with the appendage material (e.g., via hydrolysis), causing the appendage material to degrade over time, thereby altering its mechanical properties.

[0127] For a given appendage, the mechanical properties that change over time can be characterized in the form of a degradation curve. However, it is understood that surgeons may wish to adjust the degradation curve of the appendage based on considerations such as implantation location, type of surgery, etc. Therefore, as discussed in detail below, embodiments of this disclosure provide a compressible appendage with an adjustable degradation curve.

[0128] In one embodiment, a compressible appendage kit for use with a staple cartridge may be provided, and the kit may include a biocompatible appendage material and a pretreatment fluid. The appendage material is designed to be releasably held on the staple cartridge body or anvil and is designed to be delivered to tissue via deployment of staples within the cartridge body. The appendage material may be in the form of a porous polymer body. Prior to implantation, a pretreatment fluid may be applied to the appendage material to change it from a stock or untreated state to a treated state, the untreated state being designed to exhibit a first degradation curve upon delivery of the appendage material to tissue, and the treated state being designed to exhibit a second degradation curve upon delivery of the appendage material to tissue. The first and second degradation curves may be different from each other.

[0129] Figure 8 This is a graph illustrating several exemplary degradation curves, one curve representing the degradation of untreated appendages and two curves representing the degradation of treated appendages. A degradation curve is a curve representing the change in the mechanical properties of a given appendage over time. As shown, the degradation rate of the treated appendage, represented by the slope of the degradation curve, can be greater or less than the degradation rate of the untreated appendage. Embodiments of the kit may include at least one pretreatment fluid configured to increase or decrease the degradation rate. In some embodiments, the kit may include multiple pretreatment fluids configured to increase or decrease the degradation rate to a predetermined degradation rate, thus allowing the user to select a pretreatment fluid designed to produce the desired degradation rate.

[0130] As discussed in more detail below, pretreatment fluids can employ various mechanisms to increase or decrease the degradation rate of adjunct materials upon delivery to tissues. In one aspect, pretreatment fluids can increase or decrease the rate of chemical reactions (e.g., hydrolysis) between aqueous body fluids and treated adjunct materials compared to untreated adjuncts. In another aspect, pretreatment fluids can be designed to promote or inhibit the absorption of adjunct materials into body fluids, thereby correspondingly increasing or decreasing the surface area of ​​the adjunct material in contact with body fluids and thus capable of chemically reacting with them. By increasing or decreasing the surface area of ​​the treated adjunct material in contact with body fluids, the degradation rate of the treated adjunct material can be increased or decreased relative to the untreated adjunct.

[0131] In another embodiment, a compressive force may be applied to the appendage material before it is attached to the cartridge or anvil to alter the connectivity between the pores of the appendage material, and thus change the relative ease with which fluid flows into the interior of the appendage material. As discussed above, the pores of the appendage material can be classified as open or closed. Open pores allow fluid to flow through, while closed pores do not. In one embodiment, the compressive force applied to the appendage material can create channels (e.g., cracks) between adjacent pores, thereby converting a closed pore into an open pore. Opening the pores in this way promotes fluid flow through the appendage material, thereby increasing the surface area of ​​the appendage material available for contact with bodily fluids, and thus increasing the degradation rate of the appendage material. In other embodiments, the compressive force applied to the appendage material can close the channels between adjacent pores, thereby converting an open pore into a closed pore. Closing the pores in this way inhibits fluid flow through the appendage material, thereby reducing the surface area of ​​the appendage material available for contact with bodily fluids, and thus reducing the degradation rate of the appendage material.

[0132] The pretreatment fluid can be applied to the appendage material in several ways. In one aspect, the appendage material can be immersed in a container containing the pretreatment fluid. In another aspect, a delivery device (e.g., a pipette, eye dropper, etc.) can be used to apply the pretreatment fluid to the appendage material. In some embodiments, the pretreatment fluid is applied to the appendage while it is being separated from the staple cartridge. In other embodiments, the pretreatment fluid is applied to the appendage while it is being held in the staple cartridge or anvil.

[0133] Compared to untreated appendages, certain embodiments of the pretreatment fluid can be designed to increase the degradation rate of the treated appendages using various mechanisms. In one aspect, the pretreatment fluid is designed to alter (e.g., raise) the pH of any aqueous tissue or fluid adjacent to the appendage material once the appendage material is implanted. As an example, the pretreatment fluid may be mixed with water contained in the fluid in contact with the appendage material and / or in the aqueous fluid adjacent to the appendage. By raising the pH at the location of the appendage, the hydrolysis rate of the appendage material can be increased, thereby increasing the degradation rate of the treated appendage. Examples of pretreatment fluids that effectively raise the pH include, but are not limited to, fluids comprising one or more salts, bicarbonates, or other buffering agents. In an embodiment, the pretreatment fluid is a solution of sodium chloride and water (e.g., a saline solution).

[0134] In another aspect, the pretreatment fluid is designed to make the appendage material more hydrophilic. As an example, the pretreatment fluid can form a coating or film on at least a portion of the surface of the appendage material (e.g., the outer surface of a pore, the inner surface of a pore, etc.). Generally, when water comes into contact with the surface of a hydrophilic material, the water tends to spread or "wet" the surface. As the degree of hydrophilicity of the surface increases, the contact area between a given volume of water and the surface increases. Therefore, increasing the hydrophilicity of the appendage can increase the degradation rate of the appendage material by increasing the contact area between the appendage material and water and / or aqueous body fluids. Examples of pretreatment fluids that effectively increase the hydrophilicity of appendage materials include, but are not limited to, wetting agents or surfactants such as loosely cross-linked polymers.

[0135] In other embodiments, crosslinking may be used alone or in combination with a pretreatment fluid to increase the hydrophilicity of the adjunct material. For example, the adjunct material may be physically crosslinked (e.g., by ultraviolet (UV) and gamma radiation irradiation and dehydrogenation heat treatment) or chemically crosslinked (e.g., using chemical crosslinking agents such as genipin and glutaraldehyde). In some embodiments, the pretreatment fluid may include one or more chemical crosslinking agents. Non-limiting examples of chemical crosslinking agents include bifunctional / polyfunctional molecules that bridge free carboxylic acid groups, amino groups, and hydroxyl groups between adjacent polymer molecules (e.g., glutaraldehyde, polyepoxides, and isocyanates), chromium sulfate, aldehydes, and isocyanates.

[0136] In an alternative embodiment, the pretreatment fluid can be designed to reduce the degradation rate of the appendage material using a variety of mechanisms compared to untreated appendages. In one aspect, the pretreatment fluid can be designed to make the appendage material more hydrophobic. As an example, the pretreatment fluid can form a coating or film on at least a portion of the surface of the appendage material (e.g., the outer surface of a pore, the inner surface of a pore, etc.). Generally, when water comes into contact with the surface of a hydrophobic material, the water tends to form beads rather than spread or “wet” the surface. As the degree of hydrophobicity of the surface increases, the contact area between a given volume of water and the surface increases. Therefore, increasing the hydrophobicity of the appendage can reduce the degradation rate of the appendage material by reducing the contact area between the appendage material and water and / or aqueous body fluids. Examples of such pretreatment fluids include, but are not limited to, siloxanes and other materials suitable for increasing the hydrophobicity of the surface of the appendage material.

[0137] In another aspect, the pretreatment fluid can be designed to form a coating that, in the treated state, deposits on at least a portion of the surface of the appendage (e.g., the outer surface of a pore, the inner surface of a pore, etc.). This coating forms a barrier that inhibits contact between the appendage material and water and / or aqueous body fluids. That is, water or aqueous fluid needs to penetrate the coating (e.g., via diffusion) and then react with and degrade the appendage material. Because the penetration of the coating is not instantaneous and takes time to complete, the presence of the coating delays the onset of hydrolysis and increases the time required to achieve a given amount of degradation, thereby reducing the degradation rate. Examples of such pretreatment fluids include, but are not limited to, oils (e.g., mineral oils, food-grade oils), greases, biocompatible lubricants, and perfluoropolyethers (PFPEs).

[0138] In another aspect, the pretreatment fluid is designed to form a sealant that seals at least a portion of the pores of the porous polymer matrix, thereby inhibiting the ingress of water or aqueous fluids into the matrix of the accessory material. As an example, the sealant formed by the pretreatment fluid may be located on the surface and / or interior of the accessory material to partially and / or completely block the corresponding flow pathways from the surface of the accessory material to the pores within the matrix of the accessory material. Therefore, the sealant can reduce the degradation rate of the accessory material by reducing the contact area between the accessory material and water and / or aqueous fluids. Examples of such pretreatment fluids include, but are not limited to, oils (e.g., mineral oils, food-grade oils), greases, biocompatible lubricants, and other highly viscous materials capable of preventing fluid inflow into the pores of the accessory material, as well as perfluoropolyethers (PFPEs).

[0139] In another aspect, the pretreatment fluid is designed to react with the associated material (e.g., via a substitution reaction) to alter the terminal functional groups of at least a portion of the polymer chains forming the porous polymer matrix in the treated state compared to the untreated state. The difference in terminal functional groups inhibits contact between the polymeric associated material and water or an aqueous body fluid. Therefore, the terminal functional groups can reduce the degradation rate of the associated material by decreasing the contact area between the associated material and water and / or the aqueous body fluid. Examples of such pretreatment fluids include, but are not limited to, brine and acids (e.g., carbonic acid).

[0140] As another example, the pretreatment fluid can be designed to terminate at least a portion of the multiple polymer chains in the porous polymer matrix. Therefore, the average length of the multiple polymer chains in the treated state is less than the average length of the multiple polymer chains in the untreated state. This reduction in average chain length decreases the contact area between the polymer adjuncts and water, thereby reducing the degradation rate of the adjuncts.

[0141] As indicated above, the appendage can be used in conjunction with a staple cartridge or anvil for tissue handling. Prior to implantation, it can be attached to the staple cartridge (e.g., such as...) Figure 6 The staple cartridge 102 shown Figure 2 The appendage material is treated with a pretreatment fluid before or after the anvil (e.g., upper jaw surface 34). Therefore, the pretreatment fluid may be present at least on the surface of the appendage material. In some embodiments, the pretreatment fluid may also flow from the surface of the appendage material to its interior or body via an open orifice. Once properly treated, and wherein the treated appendage material is releasably held on the anvil or staple cartridge, and the cartridge is positioned on surgical staples such as… Figure 1 Within the jaws of the suture device 10, the manipulator can engage the tissue between jaws 32 and 34 and actuate the device to drive the staple through the accessory material and tissue to secure the accessory material to the tissue, for example, as Figure 7 As shown.

[0142] Once implanted, the pretreated appendage can interact with water adjacent to the appendage. This water can be water alone or in the form of a mixture with other bodily fluids. Additionally, water can be located on the surface of the appendage and within at least a portion of the appendage's interior (e.g., via flow through fluid pathways, such as open pores in fluid communication with the appendage's surface).

[0143] The configuration of the pretreatment fluid determines whether it increases or decreases the degradation rate of the adjunct material. Implementations of pretreatment materials designed to increase the degradation rate of adjunct materials can do so by increasing the rate of chemical reactions (e.g., hydrolysis) between the adjunct material and water, or by increasing the contact area between water and the adjunct material. In one example, the pretreatment fluid may be mixed with water on the surface in contact with the adjunct (e.g., the outer or inner surface of a pore). The mixture of pretreatment fluid and water may have a higher pH than water alone and accelerate the rate of hydrolysis with the adjunct material. In another example, the pretreatment fluid may form a coating or film on the surface of the adjunct material (e.g., the outer or inner surface of a pore), which increases the hydrophilicity of these surfaces. The increased hydrophilicity causes water in contact with these surfaces to spread and wet the surfaces, thereby increasing the contact surface area between the adjunct material and water, and thus increasing the degradation rate of the adjunct material.

[0144] Implementations of pretreatment materials designed to increase the degradation rate of adjunct materials can increase the degradation rate of adjunct materials by reducing the contact area between water and the adjunct materials via physical or chemical mechanisms. Pretreatment fluids that physically reduce the contact area may include coatings or sealants. A coating of the pretreatment fluid can be formed by the pretreatment fluid flowing onto the surface of the adjunct material (e.g., the outer or inner surface of a pore). Once present on the surface of the adjunct material, the coating can form a physical barrier to the interaction between water and the adjunct material. A sealant can be formed by the pretreatment fluid flowing to and residing between adjacent surfaces of the adjunct material, which act as a fluid pathway between the outer surface of the adjunct material and the interior of the adjunct material. Once present in the flow pathway, the sealant can prevent water from flowing through, thereby isolating the interior regions of the adjunct material from interaction with water. Alternatively, the pretreatment fluid can react with the polymer chains forming the adjunct material to cleave these polymer chains, thereby physically reducing the length of the polymer chains and thus reducing the area of ​​the adjunct material accessible to water. Pretreatment fluids that chemically reduce the contact area may include hydrophobic agents and substitutes. Hydrophobic agents can form a coating or film on the surface of an accessory material (e.g., the outer or inner surface of a pore), which increases the hydrophobicity of these surfaces. This increased hydrophobicity causes water contacting these surfaces to pool rather than spread and wet the surface. Substituents can chemically react with the polymer chains forming the accessory material, thereby changing the terminal groups of the polymer chains to functional groups that inhibit the interaction of water with them.

[0145] Compressible implantable appendages that degrade based on healing progress

[0146] When an appendage is implanted adjacent to cut tissue, one function of the appendage can be to apply pressure to the tissue when sutured to it (e.g., a cutting suture) to promote the healing process (e.g., hemostasis). As healing progresses, it may be further desirable to reduce the pressure applied to the tissue (compression pressure) to promote angiogenesis (angiogenesis). Existing appendages can be constructed to degrade over time and thus reduce the pressure applied to the tissue through degradation due to a chemical reaction with water (hydrolysis). However, this degradation and pressure reduction are not directly related to tissue healing. Therefore, the pressure level maintained by existing degradable appendages at a given time may be unsuitable for the extent of healing progress at that time and may actually inhibit rather than promote the healing process.

[0147] Therefore, in another embodiment, an implantable appendage is provided that can be configured to exhibit reduced stiffness after implantation. This reduction in stiffness can be caused by degradation of the appendage material due to chemical reactions with physiological elements released during the healing process. Upon suture to tissue, the reduction in stiffness further results in a decrease in the pressure exerted on the tissue by the appendage. In this way, the applied pressure is correlated with the progress of tissue healing, rather than simply the duration of exposure to water.

[0148] In one embodiment, the biocompatible adhesiodine is designed to be releasably held on a staple cartridge and to be delivered to the tissue via the deployment of staples from the cartridge. The adhesiodine may be in the form of a porous polymeric body exhibiting a generally constant first compressive stiffness during a first time period from contact with the tissue. After the first time period, the porous polymeric body may also exhibit a second compressive stiffness less than the first compressive property. This second compressive property may decrease over time due to interaction (e.g., chemical reaction) with at least one physiological element released from the tissue during the healing process. In other words, as the healing process progresses, physiological elements released from the tissue during different stages of the healing process may interact with the adhesiodine, thereby causing changes in the compressive properties of the adhesiodine. Examples of interactions between the porous polymeric body and at least one physiological element, as discussed in more detail below, may include oxidation, enzymatic hydrolysis, and changes in pH adjacent to the adhesiodine.

[0149] The first time period represents the duration before the porous polymer matrix substantially reacts with at least one physiological element. That is, the duration during which any change in the first compressive stiffness is negligible (e.g., less than about 5%, less than about 4%, less than about 3%, less than about 2%, less than about 1%, etc.). Conversely, the second time period can represent the duration during which the porous polymer matrix reacts with at least one physiological element.

[0150] In one embodiment, the interaction between the porous polymer matrix and at least one physiological element leads to enzymatic degradation due to the progression of the healing response and the introduction of at least one physiological element into the healing site as the wound is remodeled.

[0151] As indicated above, in one embodiment, the interaction between the porous polymer host and at least one physiological element is an oxidation reaction, wherein the at least one physiological element is an oxygen-containing enzyme. Generally speaking, wound healing can be divided into four stages: hemostasis, inflammation, proliferation, and remodeling, and oxygen is required in almost every stage of the wound healing process, as outlined below.

[0152] Healing tissue requires energy, which is produced by the oxidative metabolism of glucose. In the aerobic metabolism of glucose, cells use oxygen to produce adenosine triphosphate (ATP), which fuels most cellular processes during wound healing. Therefore, healing tissue increases its oxygen demand. This increased oxygen consumption, in turn, leads to hypoxia and activates the initial steps of the healing process by enhancing the activity of reactive oxygen species.

[0153] During the inflammatory phase of healing, the inflammatory area is a site of significant production of reactive oxygen species (ROS). In one aspect, this production is due to phagocytosis, the uptake of cells or other materials by phagocytes as a defense against infection and invasion by foreign substances. The presence of ROS further stimulates other functions necessary for wound repair, such as the recruitment and activation of inflammatory cells, such as leukocytes (white blood cells), and the activation of fibroblasts at the wound site. Examples of leukocytes include neutrophils, basophils, eosinophils, lymphocytes, monocytes, and macrophages. These inflammatory cells are also capable of producing at least one physiological element in the form of highly reactive OOS. Examples of highly reactive OOS types may include at least one of oxygen-containing enzymes, free radicals, superoxide, and peroxides. Specific examples of ROS may include O2. 2- At least one of H2O2, NO, and HOCl is involved. At this point, a group of growth factors is released, which stimulate and attract wound healing components such as wound leukocytes and fibroblasts. Hydrogen peroxide (H2O2) can act as a mediator for these interactions. As wound healing progresses, cell proliferation and migration occur due to redox signaling by reactive oxygen species. The final step or stage of wound healing is remodeling. During remodeling, the wound gains tensile strength, and collagen fibers contract, thus causing wound contraction. The most important mediators of the collagen process are compounds released by macrophages, keratinocytes, endothelial cells, and fibroblasts / fibroblasts, all of which are oxygen-dependent.

[0154] In another implementation, reactive oxygen species can be directed from other areas of the body to the wound healing site. Generally, cells consume oxygen during their function. To keep these cells alive, the body typically provides oxygen via biological processes such as hemoglobin transport. When more cells are observed in a region of the body, angiogenesis develops blood pathways to that site to supply nutrients and oxygen to maintain the cell population.

[0155] Based on the above, it can be understood that the healing process leads to the generation and / or attraction of reactive oxygen species to the wound healing site. These reactive oxygen species can participate in the oxidative reaction with polymer adjuncts to induce polymer chain scission and contribute to the degradation of the adjuncts. Specifically, O 2- The degradation of polymers such as aliphatic polyesters can be accelerated by ester bond cleavage via nucleophilic attack. Oxygen-induced degradation chemically breaks down polymeric appendages, weakening and reducing their rigidity, thereby altering the pressure (e.g., compressive force) applied to the tissue. Because the concentration of reactive oxygen available for reaction with polymeric appendages varies with the healing process, the extent of oxygen-induced degradation of the polymeric appendages and, consequently, the pressure exerted on the tissue by the appendages, also varies with the healing process.

[0156] In another embodiment, enzyme-catalyzed hydrolysis can contribute to the degradation of the polymer matrix and the associated reduction in stiffness of the appendages. As an example, the adsorption and rate of the hydrolysis reaction can be influenced by: (i) the biochemical properties of the polymer matrix (e.g., molecular weight, chemical composition, crystallinity, surface area, etc.), (ii) the characteristics of the specific enzyme (e.g., activity, stability, local concentration, amino acid composition, and three-dimensional conformation), and (iii) medial conditions such as pH and temperature. The presence of stabilizers, activators, and / or inhibitory products in the local environment adjacent to the appendages (e.g., caused by degradation of the appendages or leaching of processing additives) can also affect the enzyme-catalyzed reaction by influencing enzyme adsorption and activity. Examples of such enzymes include, but are not limited to, hydrolases such as proteases, esterases, glycosidases, phosphatases, and other suitable hydrolases.

[0157] In another embodiment, chemical modifications to the polymer host (e.g., crosslinking, removal, or introduction of chemical groups into the polymer chain) can affect the enzymatic degradation rate. It is noteworthy that, depending on the degree of chemical modification, the modification may impair the enzyme's ability to recognize the modified polymer host. As an example, lysozyme, an enzyme responsible for degrading peptidoglycans and chitinous materials, exhibits low activity towards deacetylated chitosans with high degrees of deacetylation or crosslinked deacetylated chitosans. Examples of such enzymes include, but are not limited to, lysozyme.

[0158] In other embodiments, degradation can be linked to other in-situ physiological and chemical changes. For example, pH is one of the most affected changes in the local chemical environment due to the healing process as infection develops. The pH adjacent to the wound directly and indirectly affects at least some, or even all, of the biochemical reactions that occur during wound healing. As an example, the surface pH of the wound plays an important role in wound healing because it helps control infection and increases antimicrobial activity, oxygen release, angiogenesis, protease activity, and biotoxicity. Therefore, pH can influence routine cellular events in wound healing.

[0159] Furthermore, wounds with a high alkaline pH have a lower healing rate in both acute and chronic wounds compared to wounds with a pH closer to neutral. In other words, wound healing progresses slower as the pH rises to alkaline levels. The environment of both acute and chronic wounds progresses from an alkaline state to a neutral state, and then to an acidic state as healing begins.

[0160] Therefore, embodiments of the appendages can be configured to adopt a second stiffness in response to a decrease in pH in the local environment adjacent to the polymer matrix due to the presence of at least one physiological element. As discussed above, the pH of the water or hydrolytic biomaterial involved in the hydrolysis reaction can affect the hydrolysis rate. Specifically, the hydrolysis rate can decrease as pH decreases. Since the pH in the local environment of a wound decreases as healing progresses, it is expected that the water and hydrolytic fluids involved in the hydrolysis reaction with the appendages will also experience a decrease in pH. Therefore, the hydrolysis rate of the appendages and the relative contribution of hydrolysis to the degradation of the appendages can decrease over time compared to the relative contribution of oxidation to the degradation of the appendages. However, it is understood that the total degradation rate of the appendages caused by the combination of oxidation and hydrolysis processes can exceed the degradation rate caused by oxidation alone.

[0161] As indicated above, the appendages can be used with the staple cartridge or anvil of the surgical suture device 10 for tissue handling, such as... Figure 6 The staple cartridge 102 shown Figure 2 The anvil (e.g., upper jaw surface 34) is shown. During implantation, the adjoint material can be delivered to the tissue by deploying the staples in the staple cartridge body, securing the adjoint material to the tissue, and applying pressure (e.g., compression pressure) to the wound (e.g., cutting line) with the adjoint material.

[0162] In use, the healing process occurs within the tissue attached to the appendage. The healing process begins with hemostasis, where blood flow from the wound ceases. Generally, it is beneficial that the appendage applies relatively high pressure (compression pressure) to the wound to promote hemostasis. As discussed above, the appendage can be compressed as it is delivered to the tissue via the deployment of the pins (e.g., via the upper jaw 22 and lower jaw 34) and can expand upon release. Therefore, the appendage material can be designed to exhibit a primary stiffness upon compression, such that the compressive pressure applied by the appendage material against the tissue expansion when the appendage is deployed is sufficiently high to aid in hemostasis.

[0163] The appendage can be further configured to maintain a first stiffness at a substantially constant level during a first time period from contact with the tissue. That is, during this first time period, the appendage material may experience little to no degradation due to reactions with bodily fluids such as water or aqueous fluids (e.g., oxidation, enzymatic hydrolysis, etc.). By maintaining the first stiffness at a substantially constant level during the first time period, the compressive pressure exerted on the tissue by the appendage material also remains substantially constant.

[0164] The adjunct material can be designed to maintain a primary stiffness in a variety of ways during a first time period. As discussed above, in one aspect, the adjunct material can be treated with a pretreatment fluid to reduce its degradation rate. In another aspect, the adjunct material can be mechanically compressed to close at least a portion of its pores, thereby inhibiting the flow of bodily fluids. It is understood that one or more other mechanisms for reducing the degradation rate of the adjunct material can be employed, either alone or in any combination with those mechanisms discussed above, and can be used without limitation.

[0165] As healing progresses into the inflammation, proliferation, and remodeling phases, it is desirable to reduce the compressive stress exerted on the tissue by the appendage material to promote angiogenesis. Therefore, the appendage material can be designed to exhibit a second stiffness less than the first stiffness during a second time period following the first time period.

[0166] As an example, during the second time period, these late-stage healing phases may occur, and the tissue may release at least one physiological element to promote healing. For example, at least one physiological element may include reactive oxygen species. While reactive oxygen species are generated to provide energy for the healing process, they may also interact with the appendage material to induce degradation. Examples of such interactions may include oxidation via reaction with reactive oxygen species, hydrolysis catalyzed by enzymes (e.g., oxygen-containing enzymes), and pH changes caused by the presence of at least one physiological element in the local fluid environment of the appendage material. Oxidation may contribute to the degradation of the appendage material through polymer chain scission, while enzyme-catalyzed hydrolysis may contribute to degradation through the chemical decomposition of the polymeric appendage material. pH can contribute to degradation by influencing the degradation rate, with the increased degradation rate being maximized when the pH is relatively high (e.g., alkaline in the relatively early stages of healing). Minimal oxidation may vary depending on the healing process, as it depends on the concentration of reactive oxygen species generated during healing. Therefore, the degradation of the appendage material may vary according to the progress of healing, resulting in the appendage material exhibiting a second stiffness less than the first stiffness, which decreases as the healing process progresses. Advantageously, as noted above, the reduction in stiffness of the accessory material from the first stiffness to the second stiffness can promote angiogenesis.

[0167] Tissue thickness compensation appendages with different expansion zones

[0168] As discussed above, in some embodiments, the appendage may be configured to compensate for changes in tissue thickness during suturing, thus presenting an uncompressed (undeformed) or pre-deployed height, and may be configured to deform to one of a plurality of compressed (deformed) or deployment heights. Understandably, leakage of bodily fluids (e.g., blood, air, gastrointestinal fluids, etc.) may occur when the staple penetrates the appendage and tissue. Notably, staple penetration of the appendage can create a hole in the appendage larger than the diameter of the staple leg. Furthermore, when cutting tissue, blood may flow along the cutting line before hemostasis begins. Therefore, it is desirable to use appendage material to seal staple perforations and / or apply pressure to the staple line to promote hemostasis.

[0169] In other embodiments discussed in detail below, tissue thickness-compensating appendages are provided, which are formed of a material that swells upon exposure to moisture and have a structure in which thickness and / or pressure vary depending on location within the appendage. As an example, predefined portions of the appendage are configured to allow or restrict expansion of the appendage, thereby altering the sealing pressure applied to the tissue at those predefined portions of the appendage. In one aspect, the portion of the appendage adjacent to the corresponding initial pin line (where the pin leg is intended to penetrate the appendage material) may be configured to expand upon exposure to moisture, compared to the portion of the appendage distant from the initial pin line. This expansion of the appendage forces the appendage material into contact with the pin leg and seals the pin hole. In another aspect, the portion of the appendage adjacent to the initial cutting line (where the blade is expected to pass through and cut the tissue and appendage) may be configured to expand upon exposure to moisture, compared to the portion of the appendage distant from the initial cutting line. This expansion of the appendage allows the appendage to apply compressive pressure to the cutting line and / or the tissue region adjacent to the cutting line to promote hemostasis.

[0170] Figure 9 This is a schematic top view (e.g., xy-plane) of the upper tissue contact surface of an exemplary embodiment of a tissue thickness compensation appendage 3000 in an undeformed or pre-deployed state. The appendage 3000 includes one or more first portions 3002 and one or more second portions 3004. Although the appendage 3000 is configured to be releasably held on the staple cartridge or anvil of the suture assembly, it is shown in isolation for clarity.

[0171] The first portion 3002 of the appendage 3000 may be formed of a first material designed to exhibit a first expansion behavior in response to the reception of a unit volume of fluid. The second portion 3004 of the appendage 3000 may be configured to exhibit a second expansion behavior, different from the first expansion behavior, in response to the reception of a unit volume of fluid. The expansion behavior may include, but is not limited to, expansion volume and expansion rate. In some embodiments, the second expansion behavior of the second material gives an expansion volume and / or expansion rate greater than the corresponding expansion volume and / or expansion rate given by the first expansion behavior of the first material.

[0172] The first part 3002 may be formed from a biocompatible porous polymer material as discussed above. In contrast, the second part 3004 may be formed from a swellable material that is different from the biocompatible porous polymer material of the first part 3002. Examples of swellable materials may include, but are not limited to, hydrogels, low molecular weight polymers (e.g., polymers having an average molecular weight sufficient to be cleared from the patient's body, such as less than about 30,000 kDa), and polymers with relatively low crosslinking.

[0173] It is understood that alternative embodiments of the appendage may be configured to alter the relative expansion characteristics (e.g., expansion volume, expansion rate, etc.) of the first and second portions relative to those discussed above. For example, in response to receiving substantially the same volume of moisture, the expansion volume and / or expansion rate of the first portion of the appendage may be greater than that of the second portion. Furthermore, although not shown, alternative embodiments of the appendage may include more than two regions, each configured to swell by a different amount in response to the receipt of substantially the same volume of moisture.

[0174] As noted above, a common problem encountered when using surgical staples and appendages is leakage of one or more fluids (e.g., water, blood, air, gastrointestinal fluid, etc.) through the opening formed by the staple, even after the staple is fully formed. Therefore, in another embodiment of appendage 3000, the relative arrangement of the first portion 3002 and the second portion 3004 can be configured to apply pressure to the staple along the staple line to seal the hole formed by the staple within the appendage. Figure 9 As shown in the top view, the initial nail line 3006 extends along the length of the appendage 3000 (e.g., in the longitudinal or x-direction). The second portion 3004 is generally aligned with (e.g., generally parallel to) the initial nail line 3006 and has a width greater than that of the initial nail line 3006. In the presence of multiple initial nail lines 3006, these multiple initial nail lines can be separated from each other in the width direction (e.g., the y-direction) by the first portion 3002 and extend in the longitudinal direction (e.g., the x-direction) of the appendage, aligned with the corresponding nail line 3006.

[0175] Figure 10 yes Figure 9 An end view of the appendage 3000 (e.g., in the yz plane). As shown, the second portion 3004 may extend through the entire thickness of the appendage 3000 (e.g., in the z direction).

[0176] Before deployment and receipt of water or other physiological fluids, the appendage 3000 has a first shape. Once implanted, and upon receipt of water or other fluids, the second portion 3004 expands to form a corresponding expanded second portion 3004” and takes a second shape different from the first shape, such as... Figure 11 As shown. As a result of expansion, the second portion 3004 applies compressive force or pressure (arrow 3012) to the nail 3010, thereby partially or substantially completely sealing the hole formed by the nail 3010 passing through the appendage 3000. The expansion behavior of the correspondingly expanding second portion 3004' may be the same or different depending on the position along the nail line 3006 (e.g., along the x-direction).

[0177] In another embodiment, the relative placement of the first portion 3002 and the second portion 3004 may be configured such that the expansion of at least one of the first portion 3002 and the second portion 3004 applies pressure sufficient to provide hemostasis along and / or adjacent tissue cutting lines. Figure 12 This is a top view schematic diagram of the upper tissue contact surface of another exemplary embodiment of the tissue thickness compensation appendage 3020 in an undeformed or pre-deployed state. Figure 13 yes Figure 12 End view of accessory 3020. Figure 14 This is an end view of the appendage 3020 in its deformed or deployed state. Although the appendage 3000 is configured to be releasably held on the staple cartridge or anvil of the suture assembly, the appendage 3020 is shown in isolation for clarity.

[0178] like Figure 12 and Figure 13 As shown, similar to appendage 3000, appendage 3020 includes a first portion 3002 and a second portion 3004. However, compared to appendage 3000, the second portion 3004 at least covers the first portion 3002 on and / or adjacent to the initial tissue incision line 3022. In other embodiments, the second portion may substantially cover the entire first portion. Appendage 3020 may be positioned on the staple cartridge of the suture assembly, wherein the first portion 3022 is adjacent to the initial tissue incision line 3022 as defined by... Figure 3 The intended paths of the blades 36 are spaced apart, and the second portion 3004 is positioned on or adjacent to the blade path / initial tissue cutting line 3022. Constructed in this way, when the appendage 3020 receives water or other fluid (arrow 3024), the second portion 3004 expands relative to the first portion 3002 to form an expanded second portion 3004', as shown. Figure 14 As shown. The expanded second portion 3004' applies pressure (arrow 3026) along the cutting line 3022 to promote hemostasis. The expansion behavior of the corresponding expanded second portion 3004' may be the same or different depending on the position along the blade path / initial tissue cutting line 3022.

[0179] In another embodiment of appendages 3000 and 3020, the second portion 3004 may be formed of a porous solid material and contained in a compressed state within a fluid-soluble capsule. The capsule may be configured to degrade relatively rapidly in response to contact with water and / or other physiological fluids after a predetermined time period (e.g., approximately several seconds to several minutes) to release the second portion from the capsule. Advantageously, this encapsulation provides timed release control over pressure applied to tissue by appendages 3000 and 3020.

[0180] In other implementations, tissue thickness-compensating appendages may be configured to degrade over time, thereby providing a short-term mechanism for tissue compression. As discussed in more detail below, such appendages may be combined with other mechanisms that provide relatively long-term compression, such as nails. These short-term and long-term compression mechanisms can work together to promote tissue healing.

[0181] Generally, the mechanical properties of bioabsorbable appendages change (e.g., decrease) over time as the degree of degradation increases. In one embodiment, appendage 3020 may be configured to degrade at a rate that maintains sufficient compression (e.g., through expansion of the second portion 3004') to allow the body to coagulate / clot bleeding within the region of the cutting line 3022. The compressive pressure provided by the nail can be provided to further enhance the cutting line for a longer duration and at a lower magnitude compared to the compressive pressure provided by the appendage. Advantageously, the relatively high compressive pressure provided by appendage 3020 promotes coagulation in the short term, while the relatively low compressive pressure provided by the nail provides enhancement in the long term without restricting blood flow to the cutting line 3022.

[0182] In another embodiment, a tissue thickness compensation appendage 3030 is provided and the tissue thickness compensation appendage is configured to work in combination with the nail 3036 to prevent the appendage 3030 from retracting from contact with the tissue 3038 after expansion. Figure 15 This is a schematic side sectional view of a suture assembly 3040 in a pre-firing configuration, which includes a first jaw having an anvil 3042 (partially shown) opposite a staple cartridge 3044 that accommodates a plurality of staples (only one staple 3036 is shown). An appendage 3020 is positioned on the anvil 3042 and includes one or more first portions 3032 below one or more second portions 3034. The first portions 3032 contact the anvil 3042, and the second portions 3034 are spaced apart from the anvil 3042 and face the tissue. In this pre-firing configuration, the appendage 3020 has a total initial thickness s. o As shown in the figure, the first part 3032 and the second part 3034 are generally planar. However, other non-planar configurations can be used without restriction. Furthermore, although... Figure 15 The embodiment shows an appendage positioned on the anvil, but in an alternative embodiment, the appendage may be positioned on the staple cartridge.

[0183] In operation, such as Figure 16 As shown, tissue 3038 is clamped between anvil 3042 and staple cartridge 3044, and one or more staples 3036 are fired from the staple cartridge, pass through appendage 330, and enter tissue 3038, thereby stapled appendage 3030 to tissue 3038. Figure 17As further shown, appendage 3030 and tissue 3038 are subsequently released from suture assembly 3040 after nail firing. Due to the removal of the clamping force applied by suture assembly 3040, the total thickness of appendage 3030 after release from suture assembly 3040 decreases from the initial thickness s. o Increase to the implantation thickness s1. Tissue 3038 has a thickness t1.

[0184] After being sutured to tissue 3038, the appendage receives a unit volume of fluid (e.g., water and / or other physiological fluids). At least one of the first portion 3032 and the second portion 3034 is formed of a polymer configured to expand in response to the reception of water and / or other physiological fluids. In some embodiments, the first portion 3032 may be formed of a hygroscopic, swelling polymer. The second portion 3034 may be formed of a semi-porous membrane. The first portion 3032 is configured to expand according to a first expansion behavior in response to the reception of a unit volume of fluid. The second portion 3034 may be configured to expand according to a second expansion behavior different from the first expansion behavior in response to the reception of a unit volume of fluid. The second portion 3034 may also cover the first portion 3032 and may be mechanically attached to the first portion (e.g., by a biocompatible adhesive or other fixation mechanism). Since the second portion 3034 is semi-porous, a portion of the water and / or other physiological fluids received by the second portion 3034 and not absorbed can flow through the second portion 3034 (e.g., via open pores) so that they can be received by the first portion 3032.

[0185] The expansion of the first portion 3032 applies a first pressure (e.g., compressive pressure) to the tissue 3038, and the expansion of the second portion 3034 results in a second pressure being applied to the tissue 3038. Due to the expansion of the appendage 3030 and the pressure applied by the appendage 3030 to the tissue 3038, the thickness of the appendage increases to a third thickness s2, and the thickness t2 of the tissue 3038 decreases, as... Figure 17 As shown. In an alternative embodiment, upon receiving water and / or other physiological fluids, the second portion does not expand substantially, or expands to a degree significantly less than that of the first portion.

[0186] In other embodiments, the staple 3036 may include one or more features 3046 configured to allow the appendage 3030 to expand in a first direction (e.g., toward the tissue 3038) and to prevent the appendage 3030 from retracting in a second direction opposite to the first direction (e.g., away from the tissue 3038). Figure 16 and Figure 17As shown, one or more features 3046 may include a plurality of barbs extending along one or more legs of the nail 3036. The barbs are positioned such that, after being fired into the appendage, the barbs extend toward the base of the nail, opposite to the direction in which the nail is inserted into the tissue 3038. When the appendage 3030 expands (e.g., via expansion of the first portion 3032 and / or the second portion 3034), the barbs engage at least the second portion 3034. When the second portion 3034 is mechanically engaged with the first portion 3032, the engagement of the barbs with the second portion 3034 provides a ratcheting effect that inhibits retraction of the appendage 3030 away from the tissue 3038 after expansion of the appendage 3030.

[0187] Embodiments of any portion of any appendage of appendages 3000, 3020, and 3030 may be configured to exhibit a color change in response to expansion. As an example, the color-changing portion of appendages 3000, 3020, and 3030 may include a color-changing dye. Examples of color-changing dyes may include a water-sensitive ink designed to change color in response to at least one fluid, such as water and lipids. In another embodiment, the expandable portion of appendages 3030, 3020, and 3030, formed of a water- or lipid-sensitive polymer, may be in a thin and dry state when not deployed, and expand to a higher state upon deployment and recombination with water.

[0188] The ability of selected portions of appendages 3000, 3020, and 3030 to exhibit color changes upon expansion allows for rapid, visual identification of the expansion behavior. This facilitates confirmation that selected portions of appendages 3000, 3020, and 3030 have indeed expanded and thus accomplished functions achieved through expansion, such as nail sealing or applying pressure to cutting lines, without the need for time-consuming measurements.

[0189] Understandably, this visual recognition of the expansion of the portions of appendages 3000, 3020, and 3030 can be used for sealing nails. Understandably, since the mass of the portions of appendages 3000, 3020, and 3020 that exhibit color changes is constant, the increase in volume caused by expansion reduces the density of these portions.

[0190] Composite appendages degraded through multiple different mechanisms

[0191] As discussed above, in order to correlate the amount of compression applied to tissue with the amount of compression most suitable for promoting tissue healing, it is desirable to employ appendages that exhibit compression properties that degrade according to changes in the healing process. In one aspect, degradation can be correlated with the healing process by using appendage materials that degrade in response to a reaction with at least one physiological element released from the tissue during the healing process. In one example, a physiological element comprising reactive oxygen species can promote degradation by participating in an oxidative reaction with the appendage material. In another example, an enzyme released during the healing process can catalyze a hydrolytic reaction, thereby increasing the degradation rate of the appendage material through hydrolysis. This concept can be further applied in the context of composite appendages formed from two or more polymers, each polymer degrading through a different mechanism. In this way, the degradation rate of the appendage and the accompanying changes in its mechanical properties can be controlled via two mechanisms rather than a single mechanism, thus providing greater functionality.

[0192] Figure 18 This is a schematic side sectional view showing a suture assembly 3050 in a pre-firing configuration, the suture assembly including a first jaw having an anvil 3052 opposite to a staple cartridge 3054 that accommodates a plurality of staples 3056. As shown, an exemplary embodiment of the composite appendage 3060 is releasably retained on the anvil 3052 and has a thickness S. o In an alternative embodiment (not shown), the composite appendage 3060 may be releasably held on either or both of the staple cartridge or the anvil to deliver the staple to the tissue via deployment of the staple in the cartridge.

[0193] Composite appendage 3060 in Figure 19 The details are shown in more detail below. The composite appendage 3060 is formed as a porous polymer body 3062 comprising a first polymer 3064 and a second polymer 3066. The first polymer 3064 covers the second polymer 3066, and the second polymer 3066 is compressed beneath the first polymer 3064. Although the first polymer 3064 and the second polymer 3066 are shown, the appendage may comprise any number of polymers. In some embodiments, the first polymer 3064 holds at least one first drug 3070 therein. In some embodiments, the at least one first drug 3070 is a hemostatic agent. In another embodiment, the second polymer 3066 holds at least one second drug 3074 therein, which is designed to promote tissue remodeling. The compression response of the first polymer 3064 and the second polymer 3066, and the corresponding amounts of the first drug 3070 and the second drug 3074 released, are respectively... Figure 24B and Figure 24C As shown in the diagram, and discussed in more detail below, the healing mechanisms that occur over time... Figure 24A This is further illustrated in the text.

[0194] The first polymer 3064 may be designed to degrade according to a first degradation profile, which varies according to at least one of hydrolysis in response to interaction with water 3072 and heating to a physiological temperature. The first polymer 3064 may be further designed to swell in response to absorption by water 3072 and / or other physiological fluids. Examples of the first polymer 3064 include at least one of hygroscopic powder and hygroscopic foam.

[0195] The second polymer 3066 can be designed to degrade according to a second degradation curve, which varies based on at least one of oxidation, enzymatic hydrolysis, and pH changes caused by interaction with at least one physiological element 3076 released from the tissue during tissue healing progress. Figure 23 As discussed in more detail below. The second polymer 3066 was further designed to swell in response to the degradation of the first polymer 3064.

[0196] like Figure 19 and Figure 21 As shown, the first polymer 3064 covers the second polymer 3064 and thus mechanically constrains the second polymer 3064. Therefore, during the first time window A, the compressive pressure exerted by the second polymer 3064 on the tissue 3068 is relatively low and increases relatively slowly compared to the first polymer 3064. Figure 24B The relatively slow rate of increase in compressive pressure can be attributed to the moderate degradation of the first polymer 3064 and the accompanying relaxation of the constraint on the second polymer 3064.

[0197] Examples of the second polymer 3066 include a porous structure. Examples of at least one physiological element may include, but are not limited to, reactive oxygen species. Reactive oxygen species may include at least one of oxygen-containing enzymes, free radicals, superoxides, and peroxides.

[0198] In some embodiments, the second polymer 3064 holds the second drug 3074 therein. Examples of at least one second drug 3074 may include, but are not limited to, drugs designed to promote tissue remodeling. Figure 24C As shown, at least one second drug 3074 is not released before firing (conditional time window A).

[0199] In some embodiments, at least one second drug 3074 may be designed to be used for at least one of bolus release or gradual release. In one example, such as Figure 21As shown, the second drug 3074 may be encapsulated by material 3074a, which is designed to be used for the gradual release of the second drug 3074 (e.g., a material that degrades relatively slowly in response to interaction with water 3072 and / or other physiological fluids). In another example, gradual release may be provided by one or more relatively large reservoirs formed within the second polymer, which are configured to provide the release of relatively small volumes of the second drug from these reservoirs over relatively short periods of time during the degradation of the second polymer. As an example, fluid restraint devices such as valves may be used in combination with relatively large reservoirs for gradual release. In other embodiments, gradual release may be provided by a plurality of relatively small volume reservoirs, which are configured to independently release relatively small volumes of the second drug over time via the degradation of the second polymer (e.g., releasing the second drug into respective fluid pathways that are not fluidly connected to each other).

[0200] In another embodiment, bolus release of the second drug can be provided by one or more relatively large reservoirs formed within the second polymer, the one or more relatively large reservoirs being configured to provide a relatively large volume of the second drug release during the degradation of the second polymer. In an alternative embodiment, bolus containment can be provided by a plurality of smaller reservoirs, the plurality of smaller reservoirs being configured to simultaneously combine corresponding volumes of the second drug released from these reservoirs during a relatively short period of time during the degradation of the second polymer (e.g., releasing the second drug into one or more common fluid pathways).

[0201] Figure 20 This shows the immediate aftermath of firing nail 3056 through appendage 3060 and tissue 3068 (time window B). Figure 24A A schematic diagram of accessory 3060 of ). Figure 21 This is a more detailed schematic diagram of the appendage 3060. As shown, the first polymer 3064 expands in response to its interaction with water 3072. Due to this expansion, the first polymer 3064 applies a first compressive pressure 3080 to the tissue 3068.

[0202] The first polymer 3064 in time window B ( Figure 24A The first degradation profile during this period varies according to the interaction (e.g., chemical reaction) (hydrolysis) with water 3072. This configuration can be beneficial for hemostasis because it results in a first degradation profile exhibiting a relatively rapid rate of decrease from the peak of the first compressive pressure 3080. Therefore, in some embodiments, the degradation rate of the first polymer 3064 according to the first degradation profile is greater than the degradation rate of the second polymer 3066 according to the second degradation profile.

[0203] Simultaneously, the release rate 3086 of the first drug 3070 also exhibits a relatively rapid decrease, declining from its maximum value as the first polymer 3064 degrades. In other words, at least one first drug 3070 is designed for relatively rapid release. As discussed above, at least one first drug 3070 can be a hemostatic agent. Therefore, rapid release of at least one first drug 3070 can further promote rapid hemostasis.

[0204] As the second polymer 3066 is compressed beneath the first polymer 3064, the first polymer 3064 can constrain the expansion of the second polymer 3066. This in Figure 24B This is reflected in the relatively slow rate of increase of the second compressive stress 3082. However, the ability of the first polymer 3064 to constrain the second polymer 3066 weakens as the first polymer 3064 continues to degrade, and the rate of increase of the second compressive stress 2412 on the tissue 3068 increases with the progression of time within the second time window B. Therefore, the thickness of the appendage 3060 can be increased from the initial thickness S. o Increase to a first thickness S1. The tissue thickness has an initial thickness t. 组织1 The combination of the first compression pressure 3080 and the second compression pressure 3082 further promotes hemostasis, thereby providing a region 3069 for restricted blood flow for coagulation.

[0205] In some embodiments, at least one of the first and second polymers may include a hydrogel designed to expand in a larger amount than the surrounding polymer material. In this way, the resulting composite appendage can exhibit varying amounts of expansion. In this way, the appendage can apply different levels of compression to different areas of the tissue (e.g., sutures, staples, etc.). Figure 20 As shown, the composite appendage 3060 applies two different levels of compression, C1 and C2, at different areas. For example, compression C2 may be greater than compression C1 and positioned close to the cutting line, thereby increasing local pressure to seal the area until healing.

[0206] As healing progresses during the second time window B (e.g., the inflammatory phase and neutrophil release), the concentration of at least one physiological element 3076 received at the composite appendage 3060 increases. As an example, neutrophils may be released along with a corresponding physiological element from at least one physiological element 3076. Simultaneously, the degradation of the first polymer 3064 progresses over time, thereby reducing the ability of the first polymer 3064 to inhibit the interaction between the second polymer 3066 and at least one physiological element 3076. Therefore, the degradation rate of the second polymer 3066 increases, reflected in an increased release rate 2086 of at least one second drug 3074 from the second polymer 3066 as time progresses within the second time window B.

[0207] Figure 22 This indicates a predetermined time (time window C) after the nail 3056 is fired through the appendage 3060 and tissue 3068. Figure 24C A schematic diagram of accessory 3060 of ). Figure 23 This is a more detailed schematic diagram of the appendage 3060. As shown, the degradation of the first polymer 3064 is substantially complete due to a relatively low first compressive pressure 3080 and a relatively low release rate 3084 of at least one first drug 3070. That is, substantially all of the at least one first drug 3070 has been released. Furthermore, due to the decrease in the first compressive pressure 3080, the thickness of the appendage 3060 decreases from a first thickness S1 to a second thickness S2, and the thickness of the tissue 3068 decreases from the initial tissue thickness t. 组织1 Increase to the second tissue thickness t 组织2 Advantageously, the combination of the first compressive pressure 3080 and the second compressive pressure 3082 applied to tissue 3068 is at a level sufficient to allow angiogenesis.

[0208] Simultaneously, healing continues from the inflammation's progression to the proliferative and maturation phases, leading to the release of macrophages, fibroblasts, and lymphocytes, such as... Figure 24A As shown, at least one physiological element 3076 is released. With the high degradation of the first polymer 3064 during time window C, the ability of the first polymer 3064 to inhibit the interaction between the second polymer 3066 and the at least one physiological element 3076 is significantly reduced. Therefore, the at least one physiological element 3076 can freely flow into the pores of the second polymer 3066. This increases the degradation rate of the second polymer 3066, thereby reducing the second compressive pressure 3082.

[0209] The release rate 3086 of at least one second drug increases to a peak as the second polymer 3066 degrades, and then decreases from that peak. The relatively slow release of at least one second drug 3074 can promote tissue remodeling. Examples of drugs designed to promote tissue remodeling may include drugs designed to treat pain or inflammation. Further examples of such drugs may include, but are not limited to, MMP inhibitors. Examples of MMP inhibitors can be found in U.S. Patents 10,939,911 and 10,569,071 and U.S. Patent Publications 2018 / 0353659, 2018 / 0353175 and 2018 / 0353174, each of which is incorporated herein by reference in its entirety.

[0210] Those skilled in the art will understand that the present invention has been applied to conventional minimally invasive and open surgical instruments, as well as robot-assisted surgical procedures.

[0211] The device disclosed herein may be designed for single-use disposal or for multiple-use applications. However, in either case, the device can be repaired and reused after at least one use. Repair may include any combination of disassembling the device, subsequently cleaning or replacing specific parts, and subsequent reassembly steps. Specifically, the device is detachable, and any number of specific parts or components of the device can be selectively replaced or removed in any combination. After cleaning and / or replacing specific parts, the device can be reassembled for subsequent use at a repair facility or by a surgical team just before surgery. Those skilled in the art will understand that various techniques can be used for disassembly, cleaning / replacement, and reassembly of the device. The use of such techniques and the resulting repaired device are within the scope of this application.

[0212] Based on the above embodiments, those skilled in the art will recognize further features and advantages of the present invention. Therefore, the present invention should not be limited to what has been specifically shown and described, unless indicated by the appended claims. All publications and references cited herein are expressly incorporated by reference in their entirety.

Claims

1. A compressible appendage for use with a staple cartridge, the compressible appendage comprising: A biocompatible adjunct material designed to be releasably retained on a staple cartridge body and designed to be delivered to tissue via deployment of staples in the staple cartridge body, the adjunct material comprising a porous polymer body configured to exhibit a first stiffness under compression that is substantially constant during a first time period from contact with the tissue, and a second stiffness under compression during a second time period after the first time period, wherein the second stiffness is less than the first stiffness and is designed to decrease over time according to at least one of oxidation, enzyme-catalyzed hydrolysis, and pH changes caused by interaction with at least one physiological element released from the tissue during the healing progress of the tissue.

2. The appendage according to claim 1, wherein, The auxiliary material is designed to take on the second stiffness in response to oxidation caused by reaction with at least one physiological element, including reactive oxygen species.

3. The appendage according to claim 1, wherein, The accessory material is designed to oxidize in response to a reaction with at least one physiological element, including reactive oxygen species released by at least one of mature blood cells, fibroblasts, and inflammatory cells.

4. The appendage according to claim 3, wherein, The inflammatory cells are at least one of leukocytes and macrophages.

5. The accessory according to claim 2, wherein, The reactive oxygen species is at least one of oxygen-containing enzymes, free radicals, superoxides, and peroxides.

6. The appendage according to claim 2, wherein, The reactive oxygen species is O. 2- At least one of H2O2, NO and HOCl.

7. The appendage according to claim 1, wherein, The auxiliary material is designed to adopt the second stiffness in response to enzyme-catalyzed hydrolysis.

8. The appendage according to claim 7, wherein, The enzymes include lysozyme.

9. The appendage according to claim 1, wherein, The auxiliary material is designed to adopt the second stiffness in response to a decrease in pH caused by the presence of the at least one physiological element.

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