Compressible support materials with healing-dependent degradation profiles

Abstract

A compressible support material for use with a staple cartridge is provided, the compressible support material including a biocompatible support material configured to be releasably retained on the staple cartridge and delivered to tissue upon deployment of staples in the staple cartridge. The support material is formed of a porous polymeric body and configured to exhibit a first compressive stiffness that is substantially constant during a first time period from contact with the tissue. The support material is further configured to exhibit a second compressive stiffness during a second time period following the first time period. The second stiffness is less than the first stiffness and is configured to decrease over time in response to at least one of oxidation, enzyme-catalyzed hydrolysis, and changes in pH resulting from interaction with at least one physiological element released from the tissue during a healing process of the tissue.

Description

[Technical Field]

[0001] FIELD OF THE DISCLOSURE The present disclosure relates generally to compressible aids and methods of using compressible aids. [Background technology]

[0002] Surgical stapling instruments are used in surgical procedures to close openings in tissue, vessels, ducts, shunts, or other objects or body parts relevant to a particular procedure. The opening may be naturally occurring, such as a passageway in a blood vessel or an internal organ such as the stomach, or may be created by a surgeon during a surgical procedure, such as by creating a bypass or anastomosis in tissue or a vascular puncture, or by tissue incision during the stapling procedure.

[0003] Most staplers have a handle with an elongated shaft having at the end thereof a pair of movable, opposing jaws configured to hold and form staples therebetween. The staples are typically housed in a staple cartridge, which can house multiple rows of staples and is often positioned within one of the two jaws for ejection of the staples into a surgical site. During use, the jaws are positioned so that an object to be stapled is placed between them, and the jaws are closed and the device is actuated to eject and form the staples. Some staplers include a knife configured to move between the rows of staples in the staple cartridge and longitudinally incise and / or open the stapled tissue between the stapled rows.

[0004] Although surgical staplers have improved over the years, they still present many problems. One common problem is that staples can leak because they create holes as they penetrate the tissue or other object into which they are placed. Blood, air, gastrointestinal fluids, and other fluids can seep through the openings created by the staples even after they are fully formed. The tissue being treated can also become inflamed due to the trauma caused by stapling. Summary of the Invention [Problem to be solved by the invention]

[0005] Although a variety of implantable materials have been developed for use in conjunction with various stapled tissues, there remains a need for improved materials that address some of the aforementioned problems. [Means for solving the problem]

[0006] Generally, compressible support materials and methods for repairing tissue are provided. In one embodiment, a compressible support material kit for use with a staple cartridge is provided, the kit including a biocompatible support material and a pretreatment fluid. The biocompatible support material is configured to be releasably retained on the staple cartridge and delivered to tissue by deployment of staples in the staple cartridge. The support material can be in the form of a porous polymer body. The pretreatment fluid is configured to be applied to the support material to transform the support material from an untreated state to a treated state. The untreated support material is configured to exhibit a first degradation profile when delivered to tissue. The treated support material is configured to exhibit a second degradation profile when delivered to tissue, the second degradation profile being different from the first degradation profile.

[0007] The pretreatment fluid may have various configurations. In one embodiment, the pretreatment fluid may be configured to increase the degradation rate of the second degradation profile relative to the first degradation profile. In another embodiment, the pretreatment fluid may be configured to increase the pH of the supplemental material adjacent to the supplemental material when delivered to tissue. In another aspect, the pretreatment fluid may be configured to increase the degree of hydrophilicity of the supplemental material in the processed state. In another embodiment, the pretreatment fluid may be configured to decrease the degradation rate of the second degradation profile relative to the first degradation profile. In another embodiment, the pretreatment fluid may be configured to form a coating that is deposited on at least a portion of the supplemental material in the processed state. In yet another embodiment, the pretreatment fluid may be configured to react with the supplemental material to change the terminal functional groups of at least some of the polymer chains that form the porous polymer body in the processed state. In another aspect, the pretreatment fluid may be configured to increase the degree of hydrophobicity of the supplemental material in the processed state compared to the untreated state. In yet another embodiment, the pretreatment fluid may be configured to form a sealant that seals at least a portion of the pores in the porous polymer body. In other aspects, the pretreatment fluid can be configured to terminate at least a portion of the polymer chains of the porous polymer body such that the average length of the polymer chains in the polymer body in the treated state is shorter than the average length of the polymer chains in the polymer body in the untreated state.

[0008] In another embodiment, a surgical method is provided that includes treating an untreated biocompatible adjunct material comprising a porous polymer body to produce a treated adjunct material having an altered degradation profile relative to the untreated adjunct material. The method also includes releasably retaining the treated adjunct material on a staple cartridge and actuating a surgical stapling device having the staple cartridge and the treated adjunct material thereon to staple the treated adjunct material to tissue.

[0009] In one embodiment, treating the biocompatible auxiliary material includes immersing the auxiliary material in a pretreatment fluid. The altered degradation profile can have a degradation rate that is greater than the degradation profile of the untreated auxiliary material. In another embodiment, treating the auxiliary material increases the pH adjacent to the treated auxiliary material when delivered to tissue. In another embodiment, treating the auxiliary material increases the degree of hydrophilicity of the treated auxiliary material compared to the untreated auxiliary material. In another embodiment, the altered degradation profile has a degradation rate that is less than the degradation profile of the untreated auxiliary material.

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

[0011] In another embodiment, treating the auxiliary material includes applying a pretreatment fluid that terminates at least a portion of the polymer chains of the polymer bodies such that the average length of the polymer chains of the treated auxiliary material is shorter than the average length of the polymer chains of the polymer bodies of the untreated auxiliary material, and the degradation rate of the second degradation profile is increased relative to the first degradation profile.

[0012] In another embodiment, a compressible support material for use with a staple cartridge is provided, the compressible support material including a biocompatible support material configured to be releasably retained on the staple cartridge and delivered to tissue upon deployment of staples in the staple cartridge. The support material is formed of a porous polymer body and configured to exhibit a first compressive stiffness that is substantially constant during a first time period upon contact with the tissue. The support material is further configured to exhibit a second compressive stiffness during a second time period following the first time period. The second stiffness is less than the first stiffness and is configured to decrease over time in response to at least one of oxidation, enzyme-catalyzed hydrolysis, and changes in pH resulting from interaction with at least one physiological element released from the tissue during the healing process.

[0013] In one embodiment, the support material is configured to assume a second stiffness in response to oxidation resulting from reaction with a physiological element including a reactive oxygen species. In another embodiment, the support material is configured to oxidize in response to reaction with a reactive oxygen species released by a mature blood cell or a fibrocyte. The reactive oxygen species may include superoxide. In another embodiment, the support material is configured to oxidize in response to reaction with a reactive oxygen species released by an inflammatory cell. The inflammatory cell may be at least one of a leukocyte, a neutrophil, a basophil, an eosinophil, a lymphocyte, a monocyte, and a macrophage. In another embodiment, the reactive oxygen species is at least one of an oxygen-containing enzyme, a free radical, a superoxide, and a peroxide. In another embodiment, the reactive oxygen species is O2 - , H2O2, NO, and HOCl.

[0014] In another embodiment, the supplemental material is configured to adopt the second stiffness in response to hydrolysis catalyzed by an enzyme. The enzyme can be lysozyme. In another embodiment, the supplemental material is configured to adopt the second stiffness in response to a decrease in pH due to the presence of at least one physiological factor.

[0015] In another aspect, a stapling assembly is provided, the stapling assembly including a staple cartridge, an anvil, and an auxiliary material. The staple cartridge has a plurality of staples disposed therein, the staples arranged in staple rows and configured to be deployed into tissue. The staple cartridge also includes a knife slot extending through the staple cartridge between the staple rows to receive a knife for severing the tissue along a cut line. The anvil is positioned opposite the staple cartridge. The auxiliary material is configured to be releasably retained on the staple cartridge or the anvil. The auxiliary material can be in the form of a biocompatible porous polymeric material configured to be delivered to tissue upon deployment of the plurality of staples from the staple cartridge. The auxiliary material can have a first shape, and at least one first portion of the auxiliary material can be configured to exhibit a first expansion behavior in response to receipt of a unit volume of fluid, and at least one second portion of the auxiliary material can be configured to exhibit a second expansion behavior in response to receipt of a unit volume of fluid, the second expansion behavior being different from the first expansion behavior, such that the auxiliary material assumes a second shape different from the first shape. The difference between the first expansion behavior and the second expansion behavior can be configured so that the support material applies different pressures to different portions of the tissue being stapled.

[0016] In one embodiment, the amount of expansion of the support material is configured to provide hemostasis at the cut line, hi another embodiment, the amount of expansion of the support material is configured to seal holes formed in the issue by the staples as the staples are ejected into the tissue.

[0017] In another embodiment, the at least one second portion of the auxiliary material is positioned adjacent to the knife slot, the at least one first portion of the auxiliary material is spaced a distance from the knife slot, and the second shape can be configured to apply greater pressure than the first shape.

[0018] In another embodiment, at least one second portion comprises a swellable material different from the biocompatible porous polymeric material. The swellable material may comprise a hydrogel. In another embodiment, the swellable material comprises a porous solid material, the swellable material being contained in a compressed state within a fluid-soluble capsule. The capsule may be configured to release the swellable material after a predetermined period of contact with a fluid.

[0019] In another embodiment, the expansion rate of at least one second portion of the auxiliary material in response to receiving a unit volume of fluid is greater than the expansion rate of at least one first portion of the auxiliary material in response to receiving a unit volume of fluid.

[0020] In another embodiment, at least one staple of the plurality of staples includes at least one leg including a plurality of barbs, the barbs configured to allow expansion of the support material in a first direction and inhibit retraction of the support material in a second direction opposite the first direction when the plurality of staples is ejected into the support material and tissue.

[0021] In another embodiment, the at least one second portion comprises a film covering the surface of the support material.

[0022] In another embodiment, the auxiliary material further comprises a color transition dye that changes color during expansion of the auxiliary material, and the color transition dye may be a hydrochromic ink configured to change color in response to contact with at least one of a fluid and a lipid.

[0023] In another embodiment, a supplemental material for use with a staple cartridge is provided. The supplemental material includes a biocompatible supplemental material configured to be releasably retained on the staple cartridge body and delivered to tissue upon deployment of staples within the cartridge body. The supplemental material is formed as a porous body including a first polymer and a second polymer. The first polymer is configured to degrade according to a first degradation profile in response to at least one of hydrolysis in response to interaction with water and heating to physiological temperatures. The second polymer is configured to degrade according to a second degradation profile in response to at least one of oxidation, enzyme-catalyzed hydrolysis, and a change in pH resulting from interaction with at least one physiological element released from tissue during tissue healing.

[0024] In one aspect, the first polymer is configured to expand in response to water absorption and to exert a first compressive pressure on the tissue having a magnitude dependent on the first degradation profile, and the second polymer is configured to expand in response to degradation of the first polymer and to exert a second compressive pressure on the tissue having a magnitude dependent on the first degradation profile and the second degradation profile, wherein the maximum magnitude of the second compressive pressure is less than the maximum magnitude of the first compressive pressure.

[0025] In another embodiment, the first polymer is configured to inhibit interaction of the second polymer with at least a portion of the at least one physiological element. The first polymer can overlap the second polymer.

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

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

[0028] In another embodiment, the at least one physiological component comprises a reactive oxygen species, which may comprise at least one of an oxygen-containing enzyme, a free radical, a superoxide, and a peroxide.

[0029] In another embodiment, the supplemental material includes a first drug retained by a first polymer and configured to be released during degradation of the first polymer. The first drug may include a hemostatic agent. The supplemental material may further include a second drug retained by a second polymer and configured to be released during degradation of the second polymer. The second drug may be configured to promote tissue remodeling. In another embodiment, the second drug is configured for at least one of bolus release and sustained release based on the geometric shape of the second polymer.

[0030] In one embodiment, a method for treating tissue is provided. The method includes stapling a porous biocompatible support material to tissue with one or more staples. The support material can include a first polymer and a second polymer. The support material receives at least one of water and heat sufficient to raise the temperature of the support material to a physiological temperature, thereby degrading the first polymer according to a first degradation profile. The support material receives at least one physiological element released from the tissue during the tissue healing process, thereby degrading the second polymer according to a second degradation profile in response to at least one of oxidation, enzyme-catalyzed hydrolysis, and a change in pH resulting from interaction with the at least one physiological element.

[0031] In one embodiment, a first polymer swells in response to receiving water and exerts a first compressive pressure on the tissue having a magnitude dependent on a first degradation profile, and a second polymer swells in response to degradation of the first polymer and exerts a second compressive pressure on the tissue having a magnitude dependent on at least the first and second degradation profiles, the maximum magnitude of the second compressive pressure being less than the maximum magnitude of the first compressive pressure.

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

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

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

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

[0036] In another embodiment, the supplemental material further comprises a first drug carried by the first polymer that is released during degradation of the first polymer. The first drug may be a hemostatic agent.

[0037] In another embodiment, the supplemental material further comprises a second drug carried by the second polymer that is released during degradation of the second polymer, the second drug being capable of promoting tissue remodeling.

[0038] In another embodiment, the method further comprises at least one of bolus and sustained release of the second drug based on the geometry of the second polymer. [Brief explanation of the drawings]

[0039] The present invention will be more fully understood from the following detailed description when read in conjunction with the accompanying drawings, in which: [Figure 1] 1 is a perspective view of one exemplary embodiment of a conventional surgical stapling and severing instrument; [Figure 2] FIG. 2 is a top view of a staple cartridge for use with the surgical stapling and severing instrument of FIG. 1; [Figure 3] 2 is a perspective view of a firing bar of the surgical stapler of FIG. 1, the firing bar having an E-beam at its distal end. [Figure 4] FIG. 10 is a perspective view of another embodiment of a surgical stapler. [Figure 5] FIG. 10 is a perspective view of yet another embodiment of a surgical stapler. [Figure 6] A longitudinal cross-sectional view of an exemplary embodiment of a staple cartridge having exemplary support material attached to the top surface, or deck surface. [Figure 7] FIG. 7 is a partial schematic view showing the support material of FIG. 6 in a tissue-deployed state. [Figure 8] 1 is a plot showing an exemplary degradation profile of a supplemental material in an untreated state and in a treated state after application of a pretreatment fluid. [Figure 9] A schematic diagram showing a top view of the upper tissue contact surface of one exemplary embodiment of a tissue thickness compensation aid in an undeformed, i.e., pre-deployed, state configured to seal staples along the staple line. [Figure 10] 10 is a schematic diagram showing an end view of the tissue thickness compensation aid of FIG. 9 in an undeformed, i.e., undeployed, state. [Figure 11] 10 is a schematic diagram showing an end view of the tissue thickness compensation support material of FIG. 9 in a deformed, i.e., deployed, state, with the expanded portion of the support material contacting and exerting sealing pressure on the staples extending therethrough. [Figure 12] FIG. 10 is a schematic diagram showing a top view of the upper tissue contact surface of another exemplary embodiment of an auxiliary material configured to apply pressure along a tissue cut line. [Figure 13] 13 is a schematic diagram showing an end view of the tissue thickness compensation aid of FIG. 12 in an undeformed, i.e., undeployed, state. [Figure 14] 14 is a schematic diagram showing an end view of the tissue thickness compensation aid of FIG. 13 in a deformed, i.e., deployed, state. [Figure 15]FIG. 10 is a schematic diagram showing a side cross-sectional view of a staple fastening assembly in a pre-fired configuration including an anvil and a staple cartridge, with another embodiment of a tissue compensation assist material mounted on the anvil, the assist material configured to function in combination with staples fired from the staple cartridge to prevent the assist material from retracting and contacting tissue after the staples are fired. [Figure 16] 16 is a schematic diagram showing the staple fastening assembly and auxiliary material of FIG. 15 immediately after staples have been fired from the staple cartridge, passed through the auxiliary material and tissue, and released from the staple fastening assembly. [Figure 17] 17 is a schematic diagram showing the stapling assembly and support material of FIG. 16 after absorbing water and / or other physiological fluids from the body. [Figure 18] FIG. 10 is a schematic diagram illustrating a cross-sectional side view of a staple fastening assembly in a pre-fired configuration including an exemplary embodiment of a composite support material including a first polymer and a second polymer. [Figure 19] FIG. 19 is a schematic diagram showing a cross-sectional side view of the composite auxiliary material of FIG. 18. [Figure 20] 20 is a schematic diagram showing a cross-sectional side view of the composite support material of FIG. 19 connected to tissue by staples immediately after firing of the stapling assembly; FIG. [Figure 21] 21 is a schematic diagram showing an enlarged cross-sectional side view of the composite auxiliary material of FIG. 20. [Figure 22] 20 is a schematic diagram showing a cross-sectional side view of the composite support material of FIG. 19 connected to tissue by staples at a predetermined time period after firing of the stapling assembly; FIG. [Figure 23] 23 is a schematic diagram showing a cross-sectional side view of the composite auxiliary material of FIG. 22. [Figure 24]19A is a plot showing healing events as a function of time in tissue connected to a composite support material; B is a plot showing the compressive pressure exerted on tissue by the first polymer and second polymer of the composite support material of FIG. 19 as a function of time, respectively; and C is a plot showing the release rate of the first drug and the second drug carried by the first polymer and second polymer of the composite support material of FIG. 19 as a function of time, respectively. DETAILED DESCRIPTION OF THE INVENTION

[0040] Certain exemplary embodiments will now be described to provide a general understanding of the principles of the structure, function, manufacture, and use of the devices 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 devices and methods specifically described herein and illustrated in the accompanying drawings are non-limiting exemplary embodiments, and that the scope of the invention is defined solely by the claims. Features illustrated or described in connection with one exemplary embodiment may be combined with features of other embodiments. Such modifications and variations are intended to be within the scope of the present invention.

[0041] Furthermore, in this disclosure, like-named components of embodiments generally have similar characteristics, and therefore, in particular embodiments, every feature of each like-named component will not necessarily be described in full detail. Additionally, to the extent that linear or circular dimensions are used in describing the disclosed systems, devices, and methods, such dimensions are 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 to such linear and circular dimensions can be readily determined for any geometric shape. The size and shape of the systems and devices and their components may depend, at least, on the anatomical structure of the subject within which the systems and devices are to be used, the size and shape of the components with which the systems and devices are to be used, and the method and procedure for which the systems and devices are to be used.

[0042] It will be appreciated that the terms "proximal" and "distal" are used herein with reference to a user, such as a clinician, holding the handle of the instrument. Other spatial terms, such as "forward" and "rearward," similarly correspond to distal and proximal, respectively. It will be further understood that for convenience and clarity, spatial terms such as "vertical" and "horizontal" are used herein with respect to the drawings. However, surgical instruments are used in many orientations and positions, and these spatial terms are not intended to be limiting and absolute.

[0043] Various exemplary devices and methods are provided for performing surgical procedures. In some embodiments, devices and methods are provided for open surgical procedures, while in other embodiments, devices and methods are provided for laparoscopic, endoscopic, and other minimally invasive surgical procedures. These devices may be directly fired by a human user or remotely fired under the direct control of a robotic or similar manipulation tool. However, those skilled in the art will understand that the various methods and devices disclosed herein can be used in numerous surgical procedures and applications. Those skilled in the art will further recognize that the various instruments disclosed herein can be inserted into the body in any manner, such as through a natural orifice, through an incision or puncture made in tissue, or using an access device such as a trocar cannula. For example, the working portion, or end effector portion, of these instruments can be inserted directly into the patient's body or can be inserted through an access device having a working channel through which the end effector and elongate shaft of the surgical instrument can pass.

[0044] It may be desirable to use one or more biological and / or synthetic materials, referred to herein as "adjunct materials," with a surgical instrument to help improve a surgical procedure. "Adjunct materials" are also referred to herein as "adjunct materials." A variety of different surgical end effectors may benefit from the use of adjunct materials, and in some exemplary embodiments, the end effector may be a surgical stapler. When used with a surgical stapler, the adjunct material(s) may be positioned between and / or on the jaws of the stapler, incorporated into a staple cartridge disposed on the jaws, or otherwise placed proximal to the staples. Once the staples are deployed, the adjunct material(s) may remain at the treatment site with the staples, thereby providing numerous benefits. For example, the adjunct material(s) can reinforce tissue at the treatment site to prevent it from being torn or ripped by the staples at the treatment site. Tissue augmentation may be necessary to prevent the staples from tearing when the tissue is diseased, healing, or experiencing other tissue-property-altering conditions. In some cases, the supplemental material can minimize tissue movement at and near the staple puncture site, which can result from tissue deformation (e.g., lung expansion, gastrointestinal expansion, etc.) that occurs after stapling. Those skilled in the art will recognize that staple puncture sites can be stress concentrations, and the size of holes formed by the staples increases when the nearby tissue is placed under tension. Limiting tissue movement near these puncture sites can minimize the size of holes that can increase under tension. In some cases, the supplemental material can be configured to wick or absorb beneficial fluids, such as sealants, blood, adhesives, etc., that further promote healing. In some cases, the supplemental material can be configured to degrade to form a gel, such as a sealant, that further promotes healing. In some cases, the supplemental material(s) can be used to assist in sealing holes formed by staples when implanted in tissue, blood vessels, and various other objects or body parts.

[0045] In other embodiments, the auxiliary material may be used with surgical instruments configured to seal tissue without the use of staples (e.g., by using energy such as RF or ultrasound), as described, for example, in U.S. Pat. No. 10,172,611, the entirety of which is incorporated herein by reference.

[0046] In some cases, the auxiliary material can be configured to compensate for variations in tissue thickness as the auxiliary material is stapled to tissue. In such cases, the auxiliary material can also be referred to as a "tissue thickness compensating material." The tissue thickness compensating material has an uncompressed (undeformed), or pre-deployed, height that is greater than the height of the staples in the formed configuration. Further details regarding exemplary tissue thickness compensating materials can be found in U.S. Patent No. 8,864,007, which is incorporated herein by reference in its entirety. Tissue thickness compensating materials can be attached to and released from the staple cartridge in various ways, as described, for example, in U.S. Patent Nos. 9,272,406 and 10,136,890, each of which is incorporated herein by reference in its entirety.

[0047] In addition to the disclosure herein, further details regarding adjuncts and other exemplary adjuncts can be found, for example, in U.S. Pat. Nos. 10,172,611 and 10,433,846, and U.S. patent application Ser. No. 17 / 009,769 (entitled "Compressible Non-Fibrous Adjuncts," filed September 1, 2020), each of which is incorporated by reference in its entirety.

[0048] Alternatively or additionally, the support material may be configured to promote tissue ingrowth. In various situations, it is desirable to promote tissue ingrowth into the implantable support material to promote healing of treated tissue (e.g., stapled and / or incised tissue) and / or to accelerate patient recovery. More specifically, tissue ingrowth into the implantable support material may reduce the incidence, severity, and / or duration of inflammation at the surgical site. Tissue ingrowth into and / or around the implantable support material may, for example, manage the spread of infection at the surgical site. For example, ingrowth of blood vessels, particularly leukocytes, into and / or around the implantable support material may combat infection in and / or around the implantable support material and adjacent tissue. Tissue ingrowth may also aid in the patient's body's acceptance of the foreign material (e.g., the implantable support material and staples) and may reduce the likelihood that the patient's body will reject the foreign material. Rejection of the foreign material may result in infection and / or inflammation at the surgical site.

[0049] Alternatively or additionally, the supplemental material can have a drug thereon and / or therein. The drug can be varied depending on the desired effect of the drug on the surrounding tissue. By way of non-limiting example, drugs can be provided to affect hemostasis, inflammation, macrophages, and / or fibroblasts. Drugs can be mixed or combined in any combination, or drugs can be provided alone, again depending on the desired effect on the tissue. Drugs can be eluted from the supplemental material in a variety of different ways. By way of non-limiting example, coatings on the supplemental material can be modified to release drugs at different times by being absorbed at different times; the supplemental material can be modified to allow diffusion of drugs between the supplemental material at variable rates; the supplemental material can be modified in molecular weight and / or physical characteristics to release drugs at different times; etc. In addition to the disclosure herein, further details regarding drug elution aids can be found in US Pat. Nos. 9,232,941 and 10,569,071, each of which is incorporated herein by reference in its entirety.

[0050] surgical stapling instruments Various surgical instruments may be used with the adjuvants and / or medications disclosed herein. Surgical instruments may include surgical staplers. Various surgical staplers may be used, such as linear surgical staplers and circular staplers. Generally, linear staplers may be configured to form a longitudinal staple line and may include an elongated jaw to which a cartridge containing a longitudinal row of staples is coupled. The elongated jaw may include a knife or other cutting member capable of forming cuts between the staple rows along tissue held within the jaws. Generally, circular staplers may be configured to form an annular staple line and may include an annular jaw having a cartridge containing an annular row of staples. The annular jaw may include a knife or other cutting member capable of forming cuts inside the row of staples to define openings through tissue held within the jaws. Staplers may be used in a variety of different surgical procedures on a variety of tissues, for example, in thoracic or gastric surgery.

[0051] FIG. 1 illustrates an example of a linear surgical stapler 10 suitable for use with one or more adjunct materials and / or agents. Stapler 10 generally includes a handle assembly 12, a shaft 14 extending distally from a distal end 12d of handle assembly 12, and an end effector 30 at the distal end 14d of shaft 14. End effector 30 has opposed lower and upper jaws 32 and 34, although other types of end effectors may be used with shaft 14, handle assembly 12, and their associated components. Lower jaw 32 includes a staple channel 56 configured to support a staple cartridge 40. Upper jaw 34 includes an anvil face 33 facing lower jaw 32 and configured to act as an anvil to assist in deploying the staples in staple cartridge 40 (staples are hidden in FIGS. 1 and 2). At least one of the opposing lower and upper jaws 32, 34 is movable relative to the other of the lower and upper jaws 32, 34 to clamp tissue and / or other objects disposed therebetween. In some implementations, one of the opposing lower and upper jaws 32, 34 may be fixed or otherwise non-movable. In some implementations, both the opposing lower and upper jaws 32, 34 may be movable. Components of a firing system may be configured to pass through at least a portion of the end effector 30 to eject staples into the clamped tissue. In various implementations, a knife blade 36 or other cutting member may be associated with the firing system to incise tissue during the stapling procedure.

[0052] Actuation of the end effector 30 may be initiated by input from a user, such as a clinician, surgeon, etc., at the handle assembly 12. The handle assembly 12 may have many different configurations designed to manipulate and actuate the end effector 30 coupled thereto. In the illustrated embodiment, the handle assembly 12 has a pistol-grip-shaped housing 18 within which are disposed various mechanical and / or electrical components for operating various features of the instrument 10. For example, the handle assembly 12 may include a rotation knob 26 mounted adjacent its distal end 12d that 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 further include a clamping component as part of a clamping system actuated by a clamp trigger 22 and a firing component as part of a firing system actuated by a firing trigger 24. The clamp trigger 22 and the firing trigger 24 may be biased to an open position relative to the stationary handle 20 by, for example, a torsion spring. Movement of the clamp trigger 22 toward the stationary handle 20 can actuate a clamping system, described below, which can cause the jaws 32, 34 to fall toward one another, thereby clamping tissue therebetween. Movement of the firing trigger 24 can actuate a firing system, described below, which can eject staples from a staple cartridge 40 disposed therein and / or advance a knife blade 36 to cut tissue captured between the jaws 32, 34. Those skilled in the art will recognize that various configurations of mechanical, hydraulic, pneumatic, electromechanical, robotic, or other firing system components can be used to eject staples and / or cut tissue.

[0053] 2, the end effector 30 in the illustrated implementation has a lower jaw 32 that functions as a cartridge assembly or carrier and an opposing upper jaw 34 that functions as an anvil. A staple cartridge 40 having a plurality of staples therein is supported within 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 pockets (not shown), each positioned over a corresponding staple from the plurality of staples contained within the staple cartridge 40. While the upper jaw 34 can be connected to the lower jaw 32 in a variety of ways, in the illustrated implementation, the upper jaw 34 has a proximal pivot end 34p that is pivotally received within a proximal end 56p of the staple channel 56, just distal to its engagement with the shaft 14. As upper jaw 34 pivots downward, upper jaw 34 moves anvil face 33 causing staple forming pockets formed on anvil face 33 to move toward opposing staple cartridge 40 .

[0054] Various clamping components can be used to effect opening and closing of the jaws 32, 34 to selectively clamp tissue therebetween. As shown, the pivoting end 34p of the upper jaw 34 includes a closure mechanism 34c distal to its pivotal attachment with the staple channel 56. Thus, a closure tube 46, including a horseshoe-shaped opening 46a at its distal end that engages the closure mechanism 34c, selectively imparts opening motion to the upper jaw 34 during proximal longitudinal movement of the closure tube 46 and closing motion to the upper jaw 34 during distal longitudinal movement of the closure tube 46, in response to the clamp trigger 22. As noted above, in various implementations, opening and closing of the end effector 30 may be effected by relative movement of the lower jaw 32 relative to the upper jaw 34, relative movement of the upper jaw 34 relative to the lower jaw 32, or movement of both jaws 32, 34 relative to each other.

[0055] The firing component of the illustrated implementation includes a firing bar 35 having an E-beam 38 at its distal end, as shown in FIG. 3 . The firing bar 35 is contained within the shaft 14, e.g., within a longitudinal firing bar slot 14s of the shaft 14, and is guided by a firing motion from the handle 12. Actuation of the firing trigger 24 affects distal movement of the E-beam 38 through at least a portion of the end effector 30, thereby firing the staples contained within the staple cartridge 40. As shown, a guide 39 protruding from the distal end of the E-beam 38 can engage with a wedge sled 47, shown in FIG. 2 . The wedge sled 47 can then push a staple driver 48 up through staple cavities 41 formed within the staple cartridge 40. The upward movement of the staple driver 48 applies an upward force to each of the plurality of staples within the cartridge 40, thereby pushing the staples upward against the anvil face 33 of the upper jaw 34 and creating a formed staple.

[0056] In addition to firing the staples, the E-beam 38 can be configured to facilitate closing the jaws 32, 34, separating the upper jaw 34 from the staple cartridge 40, and / or severing tissue captured between the 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 the jaws 32, 34 toward each other as the firing bar 35 advances through the end effector 30. Simultaneously, a knife 36 extending between the top and bottom pins can be configured to sever tissue captured between the jaws 32, 34.

[0057] During use, the surgical stapler 10 may be placed within a cannula or port and positioned at a surgical site. Tissue to be incised and stapled may be placed between the jaws 32, 34 of the surgical stapler 10. Features of the stapler 10 may be manipulated as desired by a user to achieve a desired position of the jaws 32, 34 at the surgical site and tissue relative to the jaws 32, 34. After achieving proper positioning, the clamp trigger 22 may be pulled toward the stationary handle 20 to actuate the clamping system. The trigger 22 may actuate components of the clamping system such that the closure tube 46 advances distally through at least a portion of the shaft 14, causing at least one of the jaws 32, 34 to collapse toward the other and clamp tissue disposed therebetween. The trigger 24 can then be pulled toward the stationary handle 20 to actuate components of the firing system such that the firing bar 35 and / or E-beam 38 advance distally through at least a portion of the end effector 30, causing the firing of staples and, optionally, severing tissue captured between the jaws 32, 34.

[0058] Another example of a surgical instrument in the form of a linear surgical stapler 50 is illustrated in FIG. 4. The stapler 50 may be configured and used generally similarly to the stapler 10 of FIG. 1. Like the surgical instrument 10 of FIG. 1, the surgical instrument 50 includes a handle assembly 52 having a shaft 54 ​​extending distally therefrom and having an end effector 60 at its distal end for treating tissue. An upper jaw 64 and a lower jaw 62 of the end effector 60 may be configured to capture tissue therebetween, staple the tissue by firing staples from a cartridge 66 disposed within the lower jaw 62, and / or create an incision in the tissue. In this implementation, a mounting portion 67 at the proximal end of the shaft 54 ​​may be configured to removably mount the shaft 54 ​​and end effector 60 to the handle assembly 52. Specifically, the mating feature 68 of the attachment portion 67 can mate with a complementary mating feature 71 of the handle assembly 52. ​​The mating features 68, 71 can be configured to couple to one another via, for example, a snap-fit ​​connection, a bayonet-style connection, or the like, although any number of complementary mating features and any type of connection can be used to removably couple the shaft 54 ​​to the handle assembly 52. ​​While the entire shaft 54 ​​in the illustrated implementation is configured to be separable from the handle assembly 52, in some implementations, the attachment portion 67 can be configured to allow only a distal portion of the shaft 54 ​​to be removed. The separable coupling of the shaft 54 ​​and / or end effector 60 can allow for selective attachment of a desired end effector 60 for a particular procedure and / or reuse of the handle assembly 52 for multiple different procedures.

[0059] The handle assembly 52 may have one or more mechanisms thereon for manipulating and actuating the end effector 60. As a non-limiting example, a rotation knob 72 attached to 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 component as part of a clamping system actuated by a movable trigger 74 and a firing component as part of a firing system that may also be actuated by the trigger 74. Thus, in some implementations, movement of the trigger 74 toward the stationary handle 70 through a first range of motion may actuate the clamping component to move the opposing jaws 62, 64 toward one another and toward a closed position. In some implementations, only one of the opposing jaws 62, 64 may move toward the closed position. Further movement of the trigger 74 through a second range of motion toward the stationary handle 70 can actuate a firing component to eject staples from the staple cartridge 66 and / or advance a knife or other cutting member (not shown) to cut tissue captured between the jaws 62, 64.

[0060] An example of a surgical instrument in the form of an annular surgical stapler 80 is illustrated in FIG. 5. The stapler 80 may be generally constructed and used similarly to the linear staplers 10, 50 of FIGS. 1 and 4, although certain features are adapted for its function as a circular stapler. Like the surgical instruments 10, 50, the surgical instrument 80 includes a handle assembly 82 having a shaft 84 that extends distally from the surgical instrument 80 and has an end effector 90 at its distal end for treating tissue. The end effector 90 may include a cartridge assembly 92 and an anvil 94, each having a tissue-contacting surface having a generally circular shape. The cartridge assembly 92 and the anvil 94 may be coupled via a shaft 98 that extends from the anvil 94 of the stapler 80 to the handle assembly 82, and an actuator 85 on the handle assembly 82 may be operated to retract and advance the shaft 98 to move the anvil 94 relative to the cartridge assembly 92. Anvil 94 and cartridge assembly 92 can perform a variety of functions and can be configured to capture tissue therebetween, staple the tissue by firing staples from a cartridge 96 of cartridge assembly 92, and / or create an incision in the tissue. Generally, cartridge assembly 92 can house a cartridge containing staples that can be deployed against anvil 94 to form a circular staple pattern, for example, stapling around the circumference of a tubular body organ.

[0061] In one implementation, the shaft 98 can be configured with first and second portions (not shown) configured to be releasably coupled to one another so that the anvil 94 can be separated from the cartridge assembly 92, thereby providing greater flexibility in positioning the anvil 94 and cartridge assembly 92 within a patient. For example, the first portion of the shaft can be disposed within the cartridge assembly 92 and extend distally therefrom, terminating in a distal mating feature. The second portion of the shaft can be disposed within the anvil 94 and extend proximally therefrom, terminating in a proximal mating feature. In use, the anvil 94 and cartridge assembly 92 can be moved relative to one another by coupling the proximal and distal mating features to one another.

[0062] Handle assembly 82 of stapler 80 can be provided with various actuators that can control the operation of the stapler. For example, handle assembly 82 can be provided with a rotation knob 86 that can be rotated to facilitate positioning of end effector 90 and / or a trigger 85 for actuating end effector 90. Movement of trigger 85 through a first range of motion toward stationary handle 87 can actuate components of a clamping system to approximate the jaws (e.g., move anvil 94 toward cartridge assembly 92). Movement of trigger 85 through a second range of motion toward stationary handle 87 can actuate components of a firing system to deploy staples from staple cartridge assembly 92 and / or advance a knife to sever tissue captured between cartridge assembly 92 and anvil 94.

[0063] The illustrated examples of surgical stapling instruments 10, 50, and 80 provide only a few examples of the many different configurations and associated methods of use that may be used in conjunction with the disclosure provided herein. While the illustrated embodiments are all configured for use in minimally invasive procedures, it will be understood that instruments configured for use in open surgical procedures, such as open linear staplers as described in U.S. Patent No. 8,317,070, entitled "Surgical Stapling Devices That Produce Formed Staples Having Different Lengths," filed February 28, 2007, may also be used in conjunction with the disclosure provided herein. Further details of the illustrated embodiment, as well as further examples of surgical staplers, their components, and related methods of use, can be found in U.S. Patent Application Publication No. 2013 / 0256377, entitled "Layer Comprising Deployable Attachment Members," filed February 8, 2013; U.S. Patent No. 8,393,514, entitled "Selectively Orientable Implantable Fastener Cartridge," filed September 30, 2010; U.S. Patent No. 8,317,070, entitled "Surgical Stapling Devices That Produce Formed Staples Having Different Lengths," filed February 28, 2007; U.S. Patent No. 7,143,516, entitled "Surgical Stapling Devices That Produce Formed Staples Having Different Lengths," filed February 28, 2007;925 (titled "Surgical Instrument Incorporating EAP Blocking Lockout Mechanism," filed June 21, 2005), U.S. Patent Application Publication No. 2015 / 0134077 (titled "Sealing Materials For Use In Surgical Stapling," filed November 8, 2013), (titled "Sealing Materials for Use in Surgical Procedures," filed November 8, 2013), U.S. Patent Application Publication No. 2015 / 0134076 (titled "Hybrid Adjunct Materials for Use in Surgical Stapling," filed November 8, 2013), and U.S. Patent Application Publication No. 2015 / 0133996 (titled "Positively Charged Implantable Materials and Method of Forming the Patent application Ser. No. 2015 / 0129634 (entitled "Tissue Ingrowth Materials and Method of Using the Same" filed November 8, 2013), Patent application Ser. No. 2015 / 0133995 (entitled "Hybrid Adjunct Materials for Use in Surgical Stapling" filed November 8, 2013), Patent application Ser. No. 14 / 226,142 (entitled "Surgical Instrument Comprising a Sensor System" filed March 26, 2014), and Patent application Ser. No. 14 / 300,954 (entitled "Adjunct Materials and Methods of Using the Same in Surgical Methods for Tissue Sealing" filed June 10, 2014), each of which is incorporated herein by reference in its entirety.

[0064] Implantable support material As described above, various implantable auxiliary materials are provided for use with surgical stapling instruments. When used with a surgical stapler, the auxiliary material(s) may be positioned between and / or on the jaws of the stapler, incorporated into a staple cartridge disposed on the jaws, or otherwise positioned proximal to the staples. For example, as shown in FIG. 6, an auxiliary material 104 is positioned in contact with a staple cartridge 102. For simplicity, the auxiliary material 104 is shown schematically in FIG. 6, and various structural configurations of the auxiliary material are described in more detail below. Although partially obscured in FIG. 6, the staple cartridge 102 includes staples 106 configured to be deployed within tissue. The staples 106 may have any suitable unformed (pre-deployed) height. For example, the staples 106 may have an unformed height of approximately 2 mm to 4.8 mm. The crowns of the staples may be supported by a staple driver (not shown) prior to deployment.

[0065] In the illustrated embodiment, the support material 104 can be releasably engaged with at least a portion of the top surface, i.e., deck surface 108, of the staple cartridge 102. In some embodiments, the top surface 108 of the staple cartridge 102 can include one or more surface features. Alternatively, or additionally, one or more adhesives can be used to releasably engage the support material 104 to the staple cartridge 102. The one or more surface features and / or the one or more adhesives can be configured to engage the support material 104 to avoid undesired movement of the support material 104 relative to the staple cartridge 102 and / or to inhibit premature release of the support material 104 from the staple cartridge 102. Exemplary surface features are described in U.S. Patent Application Publication No. 2016 / 0106427, the entire contents of which are incorporated herein by reference. Further details regarding adhesives and other exemplary adhesives for temporary attachment to devices can be found in U.S. Pat. Nos. 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. Further details regarding attachment methods and other exemplary methods can be found in U.S. Patent Nos. 10,166,023 and 10,349,939, and U.S. Patent Application No. 17 / 022,520 (entitled "Method of Applying Buttress to End Effector of Surgical Stapler," filed September 16, 2020), each of which is incorporated by reference in its entirety herein.

[0066] In certain cases, the auxiliary material is compressible, allowing the auxiliary material to be compressed to various heights to compensate for different tissue thicknesses captured within the deployed staples. For example, as shown in FIG. 6 , the auxiliary material 104 has an uncompressed (non-deformed) height, i.e., pre-deployed height, and is configured to be deformed to one of a plurality of compressed (deformed) heights, i.e., deployed heights. Thus, the auxiliary material 104 can have an uncompressed height that is greater than the fired height of the staples 106 disposed within the staple cartridge 102 (e.g., the height (H) of the fired staples 106a in FIG. 7 ). That is, the auxiliary material 104 can have an undeformed state in which the maximum height of the auxiliary material 104 is greater than the maximum height of the fired staples (e.g., the staples in the formed configuration). In such cases, the auxiliary material can be referred to as a “tissue thickness compensating material.” In one embodiment, the uncompressed height of the support material 104 can 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 fired height of the staples 106. In certain embodiments, the uncompressed height of the support material 104 can be greater than 100% higher than the fired height of the staples 106, for example.

[0067] The support material can have a variety of configurations and can be formed from a variety of materials. Generally, the support material can be formed from one or more of films, foams, injection-molded thermoplastic materials, vacuum thermoforming materials, fibrous structures, additive manufacturing materials, and hybrids thereof. The support material can also include one or more biologically derived materials and one or more drugs. Each of these materials is discussed in more detail below.

[0068] The support material can be formed from a foam, such as a closed-cell foam, an open-cell foam, or a sponge. An example of how such a support material can be manufactured is from animal-derived collagen, such as porcine tendon, which is then processed and freeze-dried to obtain a foamed structure. Examples of various foam support materials are further described in the aforementioned U.S. Patent No. 8,393,514 (entitled "Selectively Orientable Implantable Fastener Cartridge," filed September 30, 2010), which is incorporated herein by reference in its entirety.

[0069] The support material may also be formed from a film made from any suitable material or combination thereof, as discussed below. The film may include one or more layers, each of which may have a different degradation rate. Furthermore, the film may have various regions formed therein, such as reservoirs capable of releasably holding one or more drugs in many different forms. The reservoirs with at least one drug disposed therein may be sealed using one or more different coating layers, which may include absorbable or non-absorbable polymers. The film may be formed in a variety of ways. For example, the film may be an extrusion film or a compression-molded film.

[0070] The auxiliary material may also be formed from an injection-molded thermoplastic material or a vacuum thermoforming material. Examples of various molding auxiliary materials are further described in U.S. Patent Application Publication No. 2013 / 0221065, entitled "Fastener Cartridge Comprising a Releasably Attached Tissue Thickness Compensator," filed February 8, 2013, which is incorporated herein by reference in its entirety. The auxiliary material may also be a fiber-based lattice. The lattice may be a woven fabric, a knitted fabric, or a nonwoven fabric, such as a meltblown, needle-punched, or thermally configured loose woven fabric. The auxiliary material may have multiple regions formed from the same or different types of lattices, which may combine to form the auxiliary material in many different ways. For example, fibers may be woven, braided, knitted, or otherwise intertwined to form regular or irregular structures. The fibers may be intertwined so that the resulting auxiliary material is relatively loose. Alternatively, the auxiliary material may include densely interwoven fibers. The auxiliary material may be in the form of a sheet, tube, spiral, or any other structure that may include softer and / or stiffer reinforcing portions. The auxiliary material may be configured so that certain regions have denser fibers, while other regions have less dense fibers. The fiber density may vary in different directions along one or more dimensions of the auxiliary material, depending on the intended use of the auxiliary material.

[0071] In other embodiments, the support material may be formed using a 3D printing process that is compatible with absorbable polymers. Non-limiting examples of suitable 3D printing processes include stereolithography (SLA or SL), material jetting, selective laser sintering (SLS), and fused filament fabrication, as will be understood by those skilled in the art.

[0072] The support material can also be a hybrid structure, such as a laminated composite or meltlocked interlocking fiber. Examples of various hybrid structural support materials are further described in U.S. Patent Application Publication No. 2013 / 0146643, entitled "Adhesive Film Laminate," filed February 8, 2013, and U.S. Patent No. 7,601,118, entitled "Minimally Invasive Medical Implant And Insertion Device And Method For Using The Same," filed September 12, 2007, both of which are incorporated herein by reference in their entireties.

[0073] material The support material based on the described technology can be formed from a variety of materials. The materials can be used in various embodiments for different purposes. The materials can be selected according to the desired treatment to be provided to the tissue to promote tissue ingrowth. The materials described below can be used to form the support material in any desired combination.

[0074] Materials may include bioabsorbable and biocompatible polymers, including homopolymers and copolymers, non-limiting examples of which include p-dioxanone (PDO or PDS), polyglycolic acid (PGA) (e.g., Dexon and Neoveil), poly(lactic-co-glycolic acid) (PLGA), polycaprolactone (PCL), polyglycolide (PGL), trimethylene carbonate (TMC), polylactic acid (PLA) (e.g., Linvatec Bioscrew and Bionx Implants Smart), and the like. Screw), poly(trimethylene carbonate) (PTMC), polyethylene diglycolate (PEDG), poly(propylene fumarate) (PPF), polyethylene ether (PEE), poly(ethylene glycol) (PEG), poly(N-isopropylacrylamide), poly(amino acids), poly(epoxy carbonate), poly(2-oxypropylene carbonate), poly(diol citrate), polymethacrylate anhydride, poly(ethoxyethylene diglycolate), poly(glycolic acid-co-lactic acid) (PLA / PGA) (e.g., the PLA / PGA materials used in Vicryl, Vicryl Rapide, PolySorb, and Biofix), polyurethanes (e.g., Elastane, Biospan, Tecoflex, Bionate, and Pellethane fibers), polyorthoesters, polyanhydrides (e.g., Gliadel and Biodel polymers), polyoxaesters, polyesteramides (e.g., REVA ReZolve stents), and tyrosine-based polyesteramides (eg, TYRX).Copolymers also include poly(lactic acid-co-polycaprolactone) (PLA / PCL) (e.g., hydrolyzed for 16-18 months), poly(L-lactic acid-co-polycaprolactone) (PLLA / PCL), poly(glycolic acid-co-trimethylene carbonate) (PGA / TMC) (e.g., Maxon), poly(glycolic acid-co-caprolactone) (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), Examples of suitable polymers include 40:60 (PCL:85% D,L-lactide:15% glycolide), and 40:60 (PCL:85% D,L-lactide:15% glycolide), PLGA-PCL-PLGA, and PLGA-PEG-PLGA.

[0075] The adjunct materials may also contain special polymeric ends such as (meth)acrylates and organically derived polymers, non-limiting examples of which include those derived from collagen (e.g., Avitene, Endoavitene, Instat, Integran, Veritas, and Microfibrillar Collagen (MFC)).

[0076] Supplements may also contain active agents, such as active cell cultures (e.g., diced autologous tissue), agents used in stem cell therapy (e.g., Biosutures and Cellerix). Hemostatic agents may also include hemostatic agents, 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-rich plasma, gelatin (e.g., Gelfilm and Gelfoam), hyaluronic acid, such as microfibers (e.g., yarns and woven fabrics) or other hyaluronic acid-based structures, or hyaluronic acid-based hydrogels. Hemostatic agents may also include polymeric sealants, such as bovine serum albumin and glutaraldehyde, human serum albumin and polyethylene crosslinker, and ethylene glycol and trimethylene carbonate. Polymeric sealants include FocalSeal surgical sealant, developed by Focal Inc.

[0077] The support materials described herein may releasably retain at least one agent therein. The agent may be selected from a number of different agents. The agent may include, but is not limited to, drugs or other agents contained within or associated with the support material that have a desired function. Examples of agents include, but are not limited to, antimicrobial agents, e.g., antibacterial agents and antibiotics, antifungal agents, antiviral agents, anti-inflammatory agents, growth factors, analgesics, anesthetics, tissue matrix degeneration inhibitors, anticancer agents, hemostatic agents, and other agents that induce a biological response.

[0078] Non-limiting examples of antibacterial agents include silver ions, aminoglycosides, streptomycin, polypeptides, bacitracin, triclosan, tetracycline, doxycycline, minocycline, demeclocycline, tetracycline, oxytetracycline, chloramphenicol, nitrofuran, furazolidone, nitrofurantoin, beta-lactams, penicillin, amoxicillin, amoxicillin + clavulanic acid, azlocillin, flucloxacillin, ticarcillin, piperacillin + tazobactam, tazocin, Biopiper TZ, Zosyn, carbapenem, imipenem, meropenem, ertapenem, doripenem, biapenem, panipenem / betamipron, quinolones, ciprofloxacin, enoxacin, gatifloxacin, gemifloxacin, levofloxacin, lomefloxacin, moxifloxacin, nalidixic acid, norfloxacin, sulfonamides, mafenide, sulfacetamide, sulfadiazine, silver sulfadiazine, sulfadimethoxine, sulfamethizole, sulfamethoxazole, sulfasalazine, sulfisoxazole, bactrim, prontosil, ansamycin, geldanamycin, herbimycin, fidaxomicin, glycopeptides, te These include icoplanin, vancomycin, telavancin, dalbavancin, oritavancin, lincosamides, clindamycin, lincomycin, lipopeptides, daptomycin, macrolides, azithromycin, clarithromycin, erythromycin, roxithromycin, telithromycin, spiramycin, oxazolidinone, linezolid, aminoglycosides, amikacin, gentamicin, kanamycin, neomycin, netilmicin, tobramycin, paromycin, paromomycin, cephalosporins, ceftobiprole, ceftolozane, cefclidin, flomoxef, monobactams, aztreonam, colistin, and polymyxin B.

[0079] Non-limiting examples of antifungal agents include triclosan, polyenes, amphotericin B, candicidin, filipin, hamycin, natamycin, nystatin, rimocidin, azoles, imidazoles, triazoles, thiazoles, allylamines, amorolfine, butenafine, naftifine, terbinafine, echinocandins, anidulafungin, caspofungin, micafungin, ciclopirox, and benzoic acid.

[0080] Non-limiting examples of antiviral agents include uncoating inhibitors such as amantadine, rimantadine, pleconaril, and the like; reverse transcription inhibitors such as acyclovir, lamivudine, antisense, fomivirsen, morpholino, ribozymes, rifampicin, and the like; and antiviral drugs such as cyanovirin-N, griffithsin, sitovirin, α-lauryl-L-arginine ethyl ester (LAE), and silver ions.

[0081] Non-limiting examples of anti-inflammatory agents include nonsteroidal anti-inflammatory drugs (e.g., salicylates, aspirin, diflunisal, propionic acid derivatives, ibuprofen, naproxen, fenoprofen, and loxoprofen), acetic acid derivatives (e.g., tolmetin, sulindac, and diclofenac), enolic acid derivatives (e.g., piroxicam, meloxicam, droxicam, and lornoxicam), anthranilic acid derivatives (e.g., mefenamic acid, meclofenamic acid, and flufenamic acid), selective COX-2 inhibitors (e.g., celecoxib (Celebrex), parecoxib, rofecoxib (Vioxx), sulfonanilides, nimesulide, and clonixin), immunoselective anti-inflammatory derivatives, corticosteroids (e.g., dexamethasone), and iNOS inhibitors.

[0082] Non-limiting examples of growth factors include factors that are cell signaling molecules that stimulate cell growth, healing, remodeling, proliferation, and differentiation. Exemplary growth factors can be short-range (paracrine), long-range (endocrine), or self-stimulating (autocrine). Further examples of growth factors include growth hormones (e.g., recombinant growth factors, neutropin, humatrope, genotropin, norditropin, saizen, omnitrope, and biosynthetic growth factors), epidermal growth factor (EGF) (e.g., inhibitors, gefitinib, erlotinib, afatinib, and cetuximab), heparin-binding EGF-like growth factors (e.g., epiregulin, betacellulin, amphiregulin, and epigen), transforming growth factor alpha (TGF-α), neuroregulins 1-4, fibroblast growth factor ( FGFs (e.g., FGF-1-2, FGF2, FGF11-14, FGF18, FGF15 / 19, FGF21, FGF23, FGF7, or keratinocyte growth factor (KGF), FGF10, or KGF2, and phenytoin), insulin-like growth factors (IGFs) (e.g., IGF-1, IGF-2, and platelet-derived growth factor (PDGF)), vascular endothelial growth factor (VEGF) (e.g., inhibitors, bevacizumab, ranibizumab, VEGF-A, VEGF-B, VEGF-C, VEGF-D, and becaplermin).

[0083] Further non-limiting examples of growth factors include cytokines such as granulocyte macrophage colony-stimulating factor (GM-CSF) (e.g., GM-CSF produced using inhibitors that inhibit inflammatory responses and recombinant DNA technology and from recombinant yeast-derived sources), granulocyte colony-stimulating factor (G-CSF) (e.g., filgrastim, lenograstim, and neupogen), tissue growth factor beta (TGF-B), leptin, and interleukins (IL) (e.g., IL-1a, IL-1b, canakinumab, IL-2, aldesleukin, interking, denileukin, diftitox, IL-3, IL-6, IL-8, IL-10, IL-11, and oprelvekin). Further non-limiting examples of growth factors include erythropoietin (e.g., darbepoetin, epocept, dynepo, epomax, neorecormon, sirapo, and retacrit).

[0084] Non-limiting examples of analgesics include narcotics, opioids, morphine, codeine, oxycodone, hydrocodone, buprenorphine, tramadol, non-narcotics, paracetamol, acetaminophen, NSAIDs, and flupirtine.

[0085] Non-limiting examples of anesthetic agents include local anesthetic agents (eg, lidocaine, benzocaine, and ropivacaine) and general anesthetic agents.

[0086] Non-limiting examples of tissue matrix degradation inhibitors that inhibit the action of metalloproteinases (MMPs) and other proteases include MMP inhibitors (e.g., exogenous MMP inhibitors, hydroxymate-based MMP inhibitors, batimastat (BB-94), ilomastat (GM6001), marimastat (BB2516), thiols, periostat (doxycycline), squaric acid, BB-1101, hydroxyurea, hydrazine, endogenous, carbamoyl phosphate, beta-lactam, and tissue inhibitors of MMPs (TIMPs)).

[0087] Non-limiting examples of anti-cancer agents include monoclonal antibodies, bevacizumab (Avastin), cyto / chemoattractants, alkylating agents (e.g., bifunctional, cyclophosphamide, mechlorethamine, chlorambucil, melphalan, monofunctional, nitrosoureas, and temozolomide), anthracyclines (e.g., daunorubicin, doxorubicin, epirubicin, idarubicin, mitoxantrone, and valrubicin), cytoskeletal disrupting agents (e.g., paclitaxel and docetaxel), epothilone agents that limit cell division by inhibiting microtubule function, inhibitors that block various enzymes necessary for cell division or specific cell functions, histone deacetylase inhibitors (e.g., vorinostat and romidepsin), topoisomerase I inhibitors (e.g., irinotecan and topotecan), topoisomerase II inhibitors (e.g., etoposide, teniposide, and tafluposide), kinase inhibitors (e.g., bortezomib, erlotinib, nib, gefitinib, imatinib, vemurafenib, and vismodegib), nucleotides themselves (e.g., azacitidine, azathioprine, capecitabine, cytarabine, doxifluridine, fluorouracil, 5-FU, adrsil, Carac, Efudix, Efudex, Fluoroplex, gemcitabine, hydroxyurea, mercaptopurine, and thioguanine), peptide antibiotics that cleave DNA and interfere with DNA unwinding / winding agents (e.g., bleomycin and actinomycin), platinum-based antitumor agents that crosslink DNA and inhibit DNA repair and / or synthesis (e.g., carboplatin, cisplatin, oxaliplatin, and eloxatin), retinoids (e.g., tretinoin, alitretinoin, and bexarotene), vinca alkaloid agents that inhibit mitosis and microtubule formation (e.g., vinblastine, vincristine, vindesine, vinorelbine), cell growth or cell proliferation inhibitors (e.g., thrombin, thrombin, thrombin)angiogenesis inhibitors that inhibit tumor expansion (e.g., axitinib (Inlyta), bevacizumab (Avastin), cabozantinib (Cometriq), everolimus (Afinitor, Zortress), lenalidomide (Revlimid), pazopanib (Votrient), ramucirumab (Cyramza), regorafenib (Stivarga), sorafenib (Nexavar), sunitinib ( Sutent), thalidomide (Synovir, Thalomid), vandetanib (Caprelsa), Zib-aflibercept (Zaltrap), antiangiogenic polysaccharides, Aplidine (dehydrodidemnin B), sapogenins, i.e., 20(S)-protopanaxadiol and 20(S)-protopanaxatriol), anti-ileus agents, prokinetic agents, immunosuppressants (e.g., tacrolimus), blood aspect modifier agents (e.g., vasodilators, Viagra, and nifedipine), 3-hydroxy-3-methyl-glutaryl-CoA (HMG CoA) reductase inhibitors (e.g., atorvastatin), and antiangiogenic agents.

[0088] Exemplary agents also include agents that passively contribute to wound healing, such as nutrients, oxygen scavengers, amino acids, collagen synthesis agents, glutamine, insulin, butyrate, and dextran. Exemplary agents also include anti-adhesion agents, non-limiting examples of which include hyaluronic acid / carboxymethylcellulose (seprafilm), oxidized regenerated cellulose (Interceed), and icodextrin 4% (Extraneal, Adept).

[0089] Exemplary agents also include those for treating coronary artery disease (CAD) (e.g., VEGF 165 Protein, AdVEGF 165 , AdVEGF 121 , and VEGF 165 plasmid) or peripheral arterial disease (PAD) (e.g., VEGF 165 Plasmid, AdVEGF 121 , SB-509 (SFP-VEGF plasmid), AdVEGF 165These include drugs that promote blood supply regeneration after rheumatoid arthritis (rheumatoid arthritis), Ad2-HIF1α-VP16 (WALK study), and Ad2-HIF1α-VP16 (WALK study).

[0090] Drug release The supplemental material based on the described technology can be associated with at least one drug in many different ways to provide a desired effect, for example, on tissue ingrowth in a desired manner. The at least one drug can be configured to be released from the supplemental material in multiple spatial and temporal patterns to trigger a desired healing process at the treatment site. The drug can be disposed within, bonded to, incorporated into, dispersed within, or otherwise associated with the supplemental material. For example, the supplemental material can have one or more regions releasably holding one or more different drugs therein. These regions can be separate reservoirs of various sizes and shapes that hold drugs therein in various ways, or other separate or continuous regions within the supplemental material. In some embodiments, the specific configuration of the supplemental material can releasably hold one drug or two or more different drugs therein.

[0091] Regardless of how the agent is disposed within the support material, an effective amount of at least one agent may be encapsulated within a container, such as a pellet, which may be in the form of a microcapsule, microbead, or any other container, which may be formed from a bioabsorbable polymer.

[0092] Targeted delivery and release of at least one drug from the auxiliary material can be achieved in many ways, depending on various factors. Generally, the at least one drug can be released from the auxiliary material as a bolus dose, such that the drug is released substantially immediately after the auxiliary material is delivered to the tissue. Alternatively, the at least one drug can be released from the auxiliary material over a specific period of time, which can be minutes, hours, days, or longer. The rate of timed release and the amount of drug released can depend on various factors, such as the degradation rate of the region from which the drug is released, the degradation rate of one or more coatings or other structures used to retain the drug within the auxiliary material, the environmental conditions of the treatment site, and various other factors. In some embodiments, when the auxiliary material has two or more drugs disposed therein, the bolus dose release of a first drug can regulate the release of a second drug so that it begins to release after the first drug has been released. The auxiliary material can contain multiple drugs, each of which can affect the release of one or more other drugs in any suitable manner.

[0093] The release of the at least one agent, either as a bolus dose or as a timed release, may occur or begin substantially immediately after the supplemental material is delivered to the tissue, or may be delayed until a predetermined time, which may depend on the structure and properties of the supplemental material or one or more regions thereof.

[0094] The supplemental material may be configured to have a structure that facilitates the distribution of an effective amount of one or more drugs retained within the supplemental material to produce a desired effect. For example, targeted delivery of a drug may be achieved by incorporating the drug into regions (e.g., reservoirs, e.g., pores or other structures) within the supplemental material formed in a pattern that allows for specific spatial distribution of the drug upon delivery. Drugs disposed within a reservoir may be incorporated into separate containers. A reservoir may contain two or more different drugs. One or more drugs may be eluted from the supplemental material in a homogeneous manner or in a heterogeneous spatial and / or temporal manner to provide a desired treatment. The structure of the supplemental material and the manner in which drugs are released from it may be used to influence or control tissue regrowth. Furthermore, tissue regrowth may be enhanced in certain locations within the treatment site and inhibited in other locations within the treatment site.

[0095] Implantable support material with adjustable degradation profile - Patents.com As described above, embodiments of the support material can be used for a variety of functions, such as tissue augmentation at the treatment site, minimizing tissue movement within and near the staple puncture site, and tissue thickness compensation. This function relies on one or more mechanical properties of the support material, such as strength (e.g., compressive strength, tensile strength), modulus / stiffness, etc., remaining at or above a predetermined level after implantation to ensure the support material's function is achieved. However, after implantation, the support material may absorb bodily fluids (e.g., water and / or aqueous fluids). Bodily fluids may chemically react with the support material (e.g., via hydrolysis) and degrade the support material over time, resulting in changes in the support material's mechanical properties.

[0096] For a given support material, the change in mechanical properties over time can be characterized in the form of a degradation profile. However, it will be appreciated that a surgeon may wish to tailor the degradation profile of the support material based on considerations such as implant location, type of surgery, etc. Accordingly, as described in detail below, embodiments of the present disclosure provide compressible support materials with tunable degradation profiles.

[0097] In one embodiment, a compressible support material kit for use with a staple cartridge is provided, which can include a biocompatible support material and a pretreatment fluid. The support material is configured to be releasably retained on the staple cartridge body or anvil and delivered to tissue by deployment of staples within the cartridge body. The support material can be in the form of a porous polymer body. Prior to implantation, a pretreatment fluid can be applied to the support material to transform the support material from a stock, or untreated, state configured to exhibit a first degradation profile upon delivery to tissue to a treated state configured to exhibit a second degradation profile upon delivery to tissue. The first degradation profile and the second degradation profile can be different from one another.

[0098] FIG. 8 is a plot showing several exemplary degradation profiles, one for untreated supplemental material and two for treated supplemental material. The degradation profile is in the form of a curve that represents the value of a mechanical property of a given supplemental material as a function of time. As shown, the degradation rate of the treated supplemental material, represented by the slope of the degradation profile, may be greater or less than the degradation rate of the untreated supplemental material. Kit embodiments may include at least one pretreatment fluid configured to increase or decrease the degradation rate. In certain 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 configured to produce a desired degradation rate.

[0099] As discussed in more detail below, the pretreatment fluid can use various mechanisms to increase or decrease the degradation rate of the supplemental material when delivered to tissue. In one aspect, the pretreatment fluid can increase or decrease the rate of chemical reaction (e.g., hydrolysis) between water-containing bodily fluids and the treated supplemental material, compared to the untreated supplemental material. In another aspect, the pretreatment fluid can be configured to promote or inhibit absorption of bodily fluids by the supplemental material, thereby increasing or decreasing, respectively, the surface area of ​​the supplemental material that can contact, and thus chemically react with, bodily fluids. By increasing or decreasing the surface area of ​​the treated supplemental material that contacts bodily fluids, compared to the untreated supplemental material, the degradation rate of the treated supplemental material can be increased or decreased relative to the untreated supplemental material.

[0100] In further embodiments, a compressive force can be applied to the auxiliary material prior to attachment to the staple cartridge or anvil to alter the connectivity between the pores of the auxiliary material and, therefore, the relative ease with which fluids can flow into the interior of the auxiliary material. As discussed above, the pores of the auxiliary material can be classified as either open or closed. Open pores can allow fluid flow therethrough, while closed pores cannot. In one embodiment, a compressive force applied to the auxiliary material can convert closed pores to open pores by forming channels (e.g., cracks) between adjacent pores. Opening the porosity in this manner can facilitate fluid flow through the auxiliary material, increasing the surface area of ​​the auxiliary material available for contact with bodily fluids, and therefore increasing the degradation rate of the auxiliary material. In other embodiments, a compressive force applied to the auxiliary material can close the channels between adjacent pores, converting open pores to closed pores. Closing the porosity in this manner can inhibit fluid flow through the auxiliary material, reducing the surface area of ​​the auxiliary material available for contact with bodily fluids, and therefore decreasing the degradation rate of the auxiliary material.

[0101] The pretreatment fluid can be applied to the supplemental material in a variety of ways. In one aspect, the supplemental material can be immersed in a container containing the pretreatment fluid. In another aspect, the pretreatment fluid can be applied to the supplemental material using a delivery device (e.g., a pipette, an eyedropper, etc.). In certain embodiments, the pretreatment fluid is applied to the supplemental material when the supplemental material is separated from the staple cartridge. In other embodiments, the pretreatment fluid is applied to the supplemental material when the supplemental material is held on the staple cartridge or anvil.

[0102] Certain embodiments of the pretreatment fluid may be configured to increase the degradation rate of the treated supplemental material compared to the untreated supplemental material using various mechanisms. In one aspect, the pretreatment fluid is configured to alter (e.g., increase) the pH of any aqueous tissue or fluid adjacent to the supplemental material upon implantation. As an example, the pretreatment fluid may be mixed with water contained in a fluid contacting the supplemental material and / or with an aqueous fluid adjacent to the supplemental material. By increasing the pH at the location of the supplemental material, the hydrolysis rate of the supplemental material can be increased, thereby increasing the degradation rate of the treated supplemental material. Examples of pretreatment fluids effective for increasing pH include, but are not limited to, fluids containing one or more salts, bicarbonates, or other buffering agents. In one embodiment, the pretreatment fluid is a solution of sodium chloride and water (e.g., saline).

[0103] In another aspect, the pretreatment fluid is configured to make the auxiliary 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 auxiliary material (e.g., the outer surface, the inner surface of the pores, etc.). Generally, when water contacts the surface of a hydrophilic material, the water tends to spread over the surface, i.e., "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 auxiliary material can increase the degradation rate of the auxiliary material due to the increased contact area between the auxiliary material and water and / or aqueous body fluids. Examples of pretreatment fluids effective in increasing the hydrophilicity of the auxiliary material include, but are not limited to, surfactants such as wetting agents or loosely crosslinked polymers.

[0104] In further embodiments, crosslinking can be used, alone or in combination with the pretreatment fluid, to increase the hydrophilicity of the supplemental material. For example, the supplemental material can be physically crosslinked (e.g., by ultraviolet (UV) and gamma radiation irradiation and dehydrothermal treatment) or chemically crosslinked (e.g., by using chemical crosslinkers such as genipin and glutaraldehyde). In certain embodiments, the pretreatment fluid can include one or more chemical crosslinkers. Non-limiting examples of chemical crosslinkers include bifunctional / multifunctional molecules that crosslink free carboxylic acid groups, amino groups, and hydroxyl groups between adjacent polymer molecules (e.g., glutaraldehyde, polyepoxides, and isocyanates), chromium sulfate, aldehydes, and isocyanates.

[0105] In alternative embodiments, the pretreatment fluid may be configured to reduce the degradation rate of the auxiliary material compared to untreated auxiliary material using various mechanisms. In one aspect, the pretreatment fluid may be configured to make the auxiliary material more hydrophilic. As an example, the pretreatment fluid may form a coating or film on at least a portion of the auxiliary material's surface (e.g., the outer surface of the pores, the inner surface, etc.). Generally, when water contacts the surface of a hydrophobic material, it tends to bead 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 auxiliary material may reduce the degradation rate of the auxiliary material due to a reduced contact area between the auxiliary material and water and / or aqueous body fluids. Examples of such pretreatment fluids include, but are not limited to, silicones and other materials suitable for increasing the hydrophobicity of the auxiliary material's surface.

[0106] In another aspect, the pretreatment fluid can be configured to form a coating that is deposited on at least a portion of the surface of the auxiliary material in a treated state (e.g., the outer surface, the inner surface of the pores, etc.). The coating forms a barrier that inhibits contact between the auxiliary material and water and / or aqueous body fluids. That is, water or aqueous fluids must penetrate the coating (e.g., by diffusion) before reacting with and degrading the auxiliary material. Because penetration of the coating is not instantaneous but requires some time to achieve, the presence of the coating delays the onset of hydrolysis, increasing the time to achieve a given amount of degradation, thereby reducing the degradation rate. Examples of such pretreatment fluids can include, but are not limited to, oils (e.g., mineral oil, food oil), greases, biocompatible lubricants, and perfluoropolyethers (PFPEs).

[0107] In a further aspect, the pretreatment fluid is configured to form a sealant that seals at least a portion of the pores of the porous polymer body, inhibiting the intrusion of water or aqueous body fluids into the bulk of the auxiliary material. As an example, the sealant formed by the pretreatment fluid can be positioned on and / or within the auxiliary material so as to partially and / or completely block the respective flow paths from the surface of the auxiliary material to the pores within the bulk of the auxiliary material. Thus, the sealant can reduce the degradation rate of the auxiliary material due to a reduced contact area between the auxiliary material and water and / or aqueous body fluids. Examples of such pretreatment fluids include, but are not limited to, oils (e.g., mineral oil, food oil), grease, biocompatible lubricants, and other highly viscous materials that can block the flow of fluids into the pores of the auxiliary material, as well as perfluoropolyethers (PFPEs).

[0108] In another aspect, the pretreatment fluid is configured to change the terminal functional groups of at least some of the polymer chains that react with the auxiliary material (e.g., by substitution reaction) to form the porous polymer body in the treated state compared to the untreated state. The difference in the terminal functional groups inhibits contact between the polymer auxiliary material and water or aqueous body fluids. Thus, the terminal functional groups can reduce the degradation rate of the auxiliary material due to a reduced contact area between the auxiliary material and water and / or aqueous body fluids. Examples of such pretreatment fluids may include, but are not limited to, saline and acids (e.g., carbonic acid).

[0109] As a further example, the pretreatment fluid can be configured to terminate at least a portion of the polymer chains in the porous polymer body. As a result, the average length of the polymer chains in the treated polymer body is shorter than the average length of the polymer chains in the untreated polymer body. The reduction in the average chain length reduces the contact area between the polymeric support material and water, thereby reducing the degradation rate of the support material.

[0110] As described above, the supplemental material can be used with a staple cartridge or anvil to treat tissue. Prior to implantation, the supplemental material can be treated with a pretreatment fluid, either before or after attachment to a staple cartridge, such as staple cartridge 102 shown in FIG. 6 or an anvil (e.g., upper jaw surface 34) shown in FIG. 2. As a result, the pretreatment fluid can be present on at least the surface of the supplemental material. In certain embodiments, the pretreatment fluid can also flow from the surface of the supplemental material to the interior or bulk of the supplemental material via open pores. Once properly treated, with the treated supplemental material releasably held on the anvil or staple cartridge, and the cartridge disposed within the jaws of a surgical stapler, such as stapler 10 or FIG. 1, the device can be manipulated to engage tissue between jaws 32, 34, as shown in FIG. 7, and actuated, thereby firing staples through the supplemental material and tissue to secure the supplemental material to the tissue.

[0111] Once implanted, the pretreated support material may interact with water adjacent to the support material. Such water may be in the form of water alone or in admixture with other bodily fluids. In addition, water may be located on the surface of the support material and within at least a portion of the interior of the support material (e.g., via flow through fluid passageways, such as open pores, that are in fluid communication with the surface of the support material).

[0112] The configuration of the pretreatment fluid determines whether the pretreatment fluid increases or decreases the degradation rate of the auxiliary material. Pretreatment material embodiments configured to increase the degradation rate of the auxiliary material can do so by increasing the rate of chemical reaction (e.g., hydrolysis) between the auxiliary material and water or by increasing the contact area between the water and the auxiliary material. In one example, the pretreatment fluid can be mixed with water that contacts the surfaces of the auxiliary material (e.g., the exterior or interior surfaces of the pores). The mixture of the pretreatment fluid and water has a higher pH than water alone, which can increase the rate of hydrolysis reaction with the auxiliary material. In another example, the pretreatment fluid can form a coating or film on the surfaces of the auxiliary material (e.g., the exterior or interior surfaces of the pores) that increases the hydrophilicity of these surfaces. The increased hydrophilicity allows water that contacts these surfaces to spread and wet the surfaces, increasing the contact surface area between the auxiliary material and the water, thereby increasing the degradation rate of the auxiliary material.

[0113] Embodiments of pretreatment materials configured to increase the degradation rate of the auxiliary material can do so by reducing the contact area between water and the auxiliary material through physical or chemical mechanisms. Pretreatment fluids that physically reduce the contact area can include coatings or sealants. A coating of pretreatment fluid can be formed by flowing the pretreatment fluid onto the surface of the auxiliary material (e.g., the outer or inner surface of a pore). Once present on the surface of the auxiliary material, the coating can form a physical barrier to interaction between water and the auxiliary material. The pretreatment fluid can flow to and form a sealant between adjacent surfaces of the auxiliary material, which serve as fluid passageways between the outer surface and the interior of the auxiliary material. Once present within the flow passageway, the sealant can block the flow of water therethrough and isolate the interior region of the auxiliary material from interaction with water. Alternatively, the pretreatment fluid can react with the polymer chains that make up the auxiliary material, severing these polymer chains and physically reducing the polymer chain length, thus reducing the area of ​​the auxiliary material that can come into contact with water. Pretreatment fluids that chemically reduce the contact area can include hydrophobic agents and displacement agents. Hydrophobic agents can form coatings or films on the surfaces of the auxiliary material (e.g., the outer or inner surfaces of the pores) that increase the hydrophobicity of those surfaces. Increased hydrophobicity causes water that contacts those surfaces to bead up rather than spreading and wetting the surface. Displacement agents can chemically react with the polymer chains that make up the auxiliary material to modify the end groups of the polymer chains with functional groups that inhibit interaction with water.

[0114] Implantable support material with compressive properties that degrades based on healing progression When implanting a support material adjacent to cut tissue, one function of the support material may be to apply pressure to the tissue (e.g., the cut line) when stapled to the tissue to promote the healing process (e.g., hemostasis). As healing progresses, it may be further desirable to reduce the pressure (compression pressure) applied to the tissue to promote blood vessel formation (angiogenesis). Existing support materials may be configured to degrade over time, thus reducing the pressure applied to the tissue through degradation due to chemical reaction with water (hydrolysis). However, such degradation and reduction in pressure do not directly correlate to tissue healing. Therefore, the level of pressure maintained by an existing degradable support material at a given time may be inappropriate for the degree of healing progress at that time and may actually inhibit rather than promote the healing process.

[0115] Thus, in a further embodiment, an implantable support material is provided that can be configured to exhibit reduced stiffness after implantation. The reduced stiffness can result from degradation of the support material due to chemical reactions with physiological elements released during the healing process. When stapled to tissue, the reduced stiffness also results in a reduced pressure applied to the tissue by the support material. In this way, the applied pressure correlates with the progress of the tissue's healing process, rather than simply the time exposed to water.

[0116] In one embodiment, the biocompatible supplemental material is configured to be releasably retained on the staple cartridge and delivered to tissue by deployment of staples in the staple cartridge. The supplemental material can be in the form of a porous polymer body that exhibits a first compressive stiffness that is substantially constant during a first period of time following contact with the tissue. The porous polymer body can further exhibit a second compressive stiffness that is less than the first compressive stiffness after the first period of time. The second compressive stiffness can 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 can interact with the supplemental material, thereby changing the compressive properties of the supplemental material. As discussed in more detail below, examples of interactions between the porous polymer body and at least one physiological element can include oxidation, enzyme-catalyzed hydrolysis, and changes in pH adjacent to the supplemental material.

[0117] The first period of time represents a period of time before the porous polymeric body has substantially reacted with at least one physiological element, i.e., a period of time 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.). In contrast, the second period of time may represent a period of time during which reaction between the porous polymeric body and at least one physiological element occurs.

[0118] In one embodiment, the interaction of the porous polymer body with at least one physiological element results in enzymatic degradation due to the progression of the healing response and the body's introduction of at least one physiological element into the healing site as the wound is remodeled.

[0119] As mentioned above, in one embodiment, the interaction between the porous polymer body and the at least one physiological element is an oxidation reaction, and the at least one physiological element is an oxygen-containing enzyme. Generally, wound healing can be divided into four stages: hemostasis, inflammation, proliferation, and remodeling, and nearly every stage in the wound healing process can require oxygen, as outlined below.

[0120] Healing tissues require energy, which is generated from the oxidative metabolism of glucose. During the aerobic metabolism of glucose, cells use oxygen to generate adenosine triphosphate (ATP), which fuels most of the cellular processes during wound healing. Therefore, healing tissues have an increased oxygen requirement. Increased oxygen consumption in turn causes hypoxia, which activates the early stages of the healing process by increasing the activity of reactive oxygen species.

[0121] During the inflammatory phase of the healing process, the inflamed area is the site for significant production of reactive oxygen species. In one aspect, this production results from phagocytosis, the ingestion of cells or other materials by phagocytes as a defense against infection and the occurrence of invasion by foreign bodies. The presence of reactive oxygen species further stimulates the recruitment and activation of inflammatory cells, such as leukocytes (white blood cells), at the wound site, as well as other functions necessary for wound repair, such as fibroblast activation. Examples of leukocytes include neutrophils, basophils, eosinophils, lymphocytes, monocytes, and macrophages. These inflammatory cells can also produce at least one physiological element in the form of highly reactive oxygen species. Examples of classes of highly reactive oxygen species may include at least one of oxygen-containing enzymes, free radicals, superoxide, and peroxide. Specific examples of reactive oxygen species include O 2- These may include at least one of HO, NO, and HOCl. At this point, a set of growth factors may be released that stimulate and attract components of wound healing (e.g., wound leukocytes and fibroblasts). Hydrogen peroxide (HO) may be a mediator of these interactions. As wound healing progresses, cell proliferation and migration occur due to redox signaling from reactive oxygen species. The final step or phase of wound healing is remodeling. During remodeling, the wound gains tensile strength and contracts as collagen fibers contract. The most prominent mediators of the collagen process are compounds released by macrophages, keratinocytes, endothelial cells, and fibroblasts / fibroblasts, all of which are oxygen-dependent.

[0122] In further embodiments, reactive oxygen species can be directed to the wound healing site from other areas within the body. In general, cells typically consume oxygen during their function. The body typically provides oxygen to cells to keep them alive through biological processes such as hemoglobin transport. As the body has more cells in an area, angiogenesis allows blood pathways to grow to the area, supplying the area with nutrients and oxygen and maintaining the cell population.

[0123] From the above, it can be seen that the healing process results in the production and / or attraction of reactive oxygen species to the wound healing site. These reactive oxygen species can participate in oxidation reactions with the polymeric support material, causing polymer chain scission and contributing to the degradation of the support material. Specifically, O 2- Oxygen-induced degradation can accelerate the degradation of polymers such as aliphatic polyesters by cleaving ester bonds through nucleophilic attack. Oxygen-induced degradation chemically degrades the polymeric support material, weakening it and reducing its stiffness, thus altering the applied pressure (e.g., compressive force) to tissue. Because the concentration of reactive oxygen species available to react with the polymeric support material is a function of the healing process, the extent of oxygen-induced degradation of the polymeric support material, and therefore the pressure applied to tissue by the support material, is also a function of the healing process.

[0124] In further embodiments, enzyme-catalyzed hydrolysis can contribute to the degradation of the polymeric body and the resulting loss of stiffness of the supplemental material. By way of example, the adsorption and rate of the hydrolysis reaction can be affected by (i) the physicochemical properties of the polymeric body (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, etc.), and (iii) medium conditions such as pH and temperature. The presence of stabilizers, activators, and / or inhibitory products (e.g., resulting from the degradation of the supplemental material or the leaching of processing additives) in the local environment adjacent to the supplemental material can also affect the enzyme-catalyzed reaction by affecting 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.

[0125] In further embodiments, chemical modification of polymeric entities (e.g., cross-linking, removal or introduction of chemical groups into the polymer chain) can affect the rate of enzymatic degradation. In particular, depending on the extent of chemical modification, it may impair the ability of enzymes to recognize the modified polymeric entities. For example, lysozyme, an enzyme involved in the degradation of peptidoglycan and chitin materials, exhibits low activity toward highly deacetylated or cross-linked chitosan. Examples of such enzymes include, but are not limited to, lysozyme.

[0126] In other embodiments, degradation may be associated with other physiological chemical changes in situ. For example, pH is one of the most affected changes in the local chemical environment due to the healing process of an infection outbreak. The pH value adjacent to a wound directly and indirectly affects at least some, and up to all, of the biochemical reactions occurring in the wound healing process. As an example, the surface pH of a wound plays an important role in wound healing because it helps control infection and increases antibacterial activity, oxygen release, angiogenesis, protease activity, and biological toxicity. Thus, pH value may affect normal cellular events in wound healing.

[0127] Furthermore, wounds with a highly alkaline pH have a lower healing rate compared to wounds with a closer-to-neutral pH, both in acute and chronic wounds. That is, as the pH increases to alkaline levels, the progress of wound healing slows. The environment of acute and chronic wounds progresses from an alkaline state to a neutral state and then to an acidic state as healing begins.

[0128] Thus, embodiments of the supplemental material may be configured to adopt a second stiffness in response to a decrease in pH in the local environment adjacent to the polymer body due to the presence of at least one physiological element. As described above, the pH of the water or aqueous biological material involved in the hydrolysis reaction may affect the hydrolysis rate. Specifically, the hydrolysis rate may decrease with a decrease in pH. Because the pH in the local environment of a wound decreases as healing progresses, a decrease in pH may be expected to be experienced by the water and aqueous fluids involved in the hydrolysis reaction with the supplemental material. Thus, the hydrolysis rate of the supplemental material, and the relative contribution of hydrolysis to the degradation of the supplemental material, may decrease over time compared to the relative contribution of oxidation to the degradation of the supplemental material. However, it may be understood that the overall degradation rate of the supplemental material resulting from the combination of oxidation and hydrolysis processes may exceed the degradation rate due to oxidation alone.

[0129] As discussed above, the adjunct material can be used with a staple cartridge or anvil of surgical stapler 10 to treat, for example, a staple cartridge, such as staple cartridge 102 shown in FIGURE 6, or an anvil (e.g., upper jaw surface 34) shown in FIGURE 2. During implantation, the adjunct material can be delivered to tissue by deploying staples within the staple cartridge body, securing the adjunct material to tissue, and causing the adjunct material to apply pressure (e.g., compressive pressure) to the wound (e.g., cut line).

[0130] During use, a healing process occurs within tissue connected to the auxiliary material. The healing process begins with hemostasis, where blood flow from the wound stops. Generally, to promote hemostasis, it is beneficial for the auxiliary material to apply a relatively high pressure (compressive pressure) to the wound. As described above, the auxiliary material can be compressed when delivered to tissue by staple deployment (e.g., by upper jaw 22 and lower jaw 34) and expand when released. Thus, when the auxiliary material is deployed, it can be configured to exhibit a first stiffness in a compressed state such that the compressive pressure exerted by the auxiliary material when it expands in contact with tissue is high enough to assist in hemostasis of the tissue.

[0131] The support material may be further configured to maintain a first stiffness at a substantially constant level during a first period of time following contact with the tissue. That is, the support material may experience little or no degradation due to reaction with bodily fluids, such as water or aqueous fluids (e.g., oxidation, enzyme-catalyzed hydrolysis, etc.), during the first period of time. By maintaining the first stiffness at a substantially constant level during the first period of time, the compressive pressure exerted by the support material on the tissue is also maintained at a substantially constant level.

[0132] The support material can be configured to maintain a first stiffness for a first period of time in various ways. As noted above, in one aspect, the support material can be treated with a pretreatment fluid, as described above, to reduce the degradation rate of the support material. In another aspect, the support material can be mechanically compressed to close at least a portion of the porosity of the support material and inhibit the flow of bodily fluids. It can be understood that one or more other mechanisms for reducing the degradation rate of the support material can be used alone or in any combination with the mechanisms described above, without limitation.

[0133] As the healing process continues through the inflammation, proliferation, and remodeling stages, it may be desirable to reduce the compressive pressure exerted on the tissue by the support material to promote blood vessel formation. Thus, the support material may be configured to exhibit a second stiffness, less than the first stiffness, during a second period following the first period.

[0134] As an example, during the second period, these later healing stages may occur, and the tissue may release at least one physiological element to promote healing. For example, the at least one physiological element may include reactive oxygen species. Reactive oxygen species are produced to provide energy for the healing process, but they may also interact with the support material, causing degradation. Examples of such interactions may include oxidation via reaction with reactive oxygen species, hydrolysis catalyzed by enzymes (e.g., oxygen-containing enzymes), and changes in pH due to the presence of at least one physiological element in the fluid environment local to the support material. Oxidation may contribute to the degradation of the support material through polymer chain scission, while enzyme-catalyzed hydrolysis may contribute to degradation through chemical breakdown of the polymeric support material. pH may contribute to degradation by affecting the rate of degradation, and the increase in degradation rate may be greatest when the pH is relatively high (e.g., alkaline relatively early in the healing process). Minimal oxidation may depend on the concentration of reactive oxygen species produced during healing and thus may be dependent on the healing process. As a result, degradation of the auxiliary material may occur as healing progresses, such that the auxiliary material exhibits a second stiffness that is less than the first stiffness, which decreases as the healing process progresses. Advantageously, as discussed above, reducing the stiffness of the auxiliary material from the first stiffness to the second stiffness may promote vascularization.

[0135] Tissue thickness compensation aid with different expansion zones As described above, in certain embodiments, the auxiliary material can be configured to compensate for variations in tissue thickness when stapled to tissue, and the auxiliary material is configured to exhibit an uncompressed (non-deformed) height, i.e., pre-deployed height, and to deform to one of a plurality of compressed (deformed) heights, i.e., deployed heights. It can be appreciated that leakage of bodily fluids (e.g., blood, air, gastrointestinal fluids, etc.) can occur when staples penetrate the auxiliary material and tissue. In particular, by penetrating the auxiliary material, the staples can form holes in the auxiliary material that are larger than the diameter of the staple legs. Furthermore, when tissue is cut before hemostasis begins, blood can flow along the cut line. Therefore, it may be desirable to use an auxiliary material to seal staple puncture holes and / or apply pressure to the staple line to facilitate hemostasis.

[0136] In a further embodiment, described in detail below, a tissue thickness-compensating support material is provided that is formed from a material that swells when exposed to moisture and has a structure in which the thickness and / or pressure varies depending on the position within the support material. As an example, certain portions of the support material are configured to allow or inhibit expansion of the support material, thereby changing the sealing pressure applied to the tissue at these certain portions of the support material. In one aspect, portions of the support material adjacent to each initial staple line, where the staple legs are intended to penetrate the support material, can be configured to expand when exposed to moisture compared to portions of the support material away from the initial staple line. This expansion of the support material can bring the support material into contact with the staple legs and seal the staple holes. In another aspect, portions of the support material adjacent to the initial cut line, where a knife is expected to pass and cut the tissue and support material, can be configured to expand when exposed to moisture compared to portions of the support material away from the initial cut line. This expansion of the support material can allow the support material to apply compressive pressure to the cut line and / or the area of ​​tissue adjacent the cut line to promote hemostasis.

[0137] 9 is a schematic diagram illustrating a top view (e.g., in the xy plane) of an upper tissue contacting surface of one exemplary embodiment of a tissue thickness compensating support material 3000 in an undeformed, or pre-deployed, state. The support material 3000 includes one or more first portions 3002 and one or more second portions 3004. The support material 3000 is configured to be releasably retained on a staple cartridge or anvil of a stapling assembly, although the support material 3000 is shown separated for clarity.

[0138] The first portion 3002 of the auxiliary material 3000 may be formed of a first material configured to exhibit a first expansion behavior in response to receiving a unit volume of fluid. The second portion 3004 of the auxiliary material 3000 may be configured to exhibit a second expansion behavior in response to receiving a unit volume of fluid, the second expansion behavior being different from the first expansion behavior. The expansion behavior may include, but is not limited to, an expansion volume and an expansion rate. In certain embodiments, the expansion volume and / or expansion rate due to the second expansion behavior of the second material is greater than the corresponding expansion volume and / or expansion rate due to the first expansion behavior of the first material.

[0139] The first portion 3002 may be formed of a biocompatible porous polymer, as described above. In contrast, the second portion 3004 may be formed of a swellable material that is different from the biocompatible porous polymer material of the first portion 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 having a relatively low degree of cross-linking.

[0140] It will be appreciated that alternative embodiments of the auxiliary material may be configured to vary the relative expansion characteristics (e.g., expansion volume, expansion rate, etc.) of the first and second portions from those described above. For example, the expansion volume and / or expansion rate of the first portion of the auxiliary material may be greater than the expansion volume and / or expansion rate of the second portion in response to the receipt of approximately the same volume of moisture. Furthermore, although not shown, additional embodiments of the auxiliary material may include three or more regions, each configured to swell a different respective amount in response to the receipt of approximately the same volume of moisture.

[0141] As discussed above, a common problem encountered when using surgical staples with support material is the seepage of one or more fluids (e.g., water, blood, air, gastrointestinal fluids, etc.) through the openings formed by the staples, even after the staples are fully formed. Accordingly, in further embodiments of the support material 3000, the relative arrangement of the first portion 3002 and the second portion 3004 can be configured to apply pressure to the staples along the staple line to seal the holes formed in the support material by the staples. As shown in the top view of FIG. 9 , the initial staple line 3006 extends along the length of the support material 3000 (e.g., in the longitudinal direction, i.e., the x-direction). The second portion 3004 is generally aligned with (e.g., generally parallel to) the initial staple line 3006 and has a width greater than that of the initial staple line 3006. In a situation where multiple initial staple lines 3006 are present, these staple lines 3006 may be separated from each other in the width direction (e.g., the y direction) by the first portion 3002, which may extend in the longitudinal direction (e.g., the x direction) of the auxiliary material and be aligned with each of the staple lines 3006.

[0142] Figure 10 is an end view (e.g., in the yz plane) of the auxiliary material 3000 of Figure 9. As shown, the second portion 3004 can extend throughout the thickness (e.g., in the z direction) of the auxiliary material 3000.

[0143] Prior to deployment and prior to receiving water or other physiological fluids, the support material 3000 has a first shape. Upon implantation and receiving water or other fluids, the second portions 3004 expand to form corresponding expanded second portions 3004'' and assume a second shape that differs from the first shape, as shown in FIG. 11 . As a result, the expansion of the second portions 3004 exerts a compressive force, or pressure (arrows 3012), on the staples 3010, thereby partially or substantially completely sealing the holes formed through the support material 3000 by the passage of the staples 3010 therethrough. The expansion behavior of each expanded second portion 3004' can be the same or different depending on the position along the staple line 3006 (e.g., along the x-direction).

[0144] In another embodiment, the relative arrangement of the first portion 3002 and the second portion 3004 can be configured such that expansion of at least one of the first portion 3002 and the second portion 3004 exerts sufficient pressure along and / or adjacent to the tissue cut line to effect hemostasis. Figure 12 is a schematic diagram illustrating a top view of an upper tissue contacting surface of another exemplary embodiment of a tissue thickness compensating support material 3020 in an undeformed, or pre-deployed, state. Figure 13 is an end view of the support material 3020 of Figure 12. Figure 14 is an end view of the support material 3020 in a deformed, or deployed, state. Although the support material 3000 is configured to be releasably retained on a staple cartridge or anvil of a stapling assembly, the support material 3020 is shown separated for clarity.

[0145] 12 and 13 , similar to the auxiliary material 3000, the auxiliary material 3020 includes a first portion 3002 and a second portion 3004. However, in contrast to the auxiliary material 3000, the second portion 3004 overlaps at least the first portion 3002 on and / or adjacent to the initial tissue cut line 3022. In other embodiments, the second portion can overlap substantially the entirety of the first portion. The auxiliary material 3020 can be positioned on a staple cartridge of a stapling assembly such that the first portion 3022 is spaced a distance from the expected path of the knife 36 that defines the initial tissue cut line 3022, as shown in FIG. 3 , and the second portion 3004 is positioned on or adjacent to the knife path / initial tissue cut line 3022. So configured, when the auxiliary material 3020 receives water or other fluid (arrows 3024), the second portion 3004 expands relative to the first portion 3002 to form expanded second portion 3004', as shown in Figure 14. The expanded second portion 3004' exerts pressure (arrows 3026) along the cut line 3022 to promote hemostasis. The expansion behavior of each expanded second portion 3004' may be the same or different depending on its position along the knife path / initial tissue cut line 3022.

[0146] In further embodiments of the support material 3000, 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 disintegrate relatively quickly in response to contact with water and / or other physiological fluids after a predetermined period of time (e.g., on the order of seconds to minutes) to release the second portion therefrom. Beneficially, such encapsulation provides time-release control of the pressure exerted by the support material 3000, 3020 on tissue.

[0147] In other embodiments, the tissue thickness compensation aid can be configured to degrade over time, providing a short-term mechanism for tissue compression. As discussed in more detail below, such aids can be combined with other mechanisms (e.g., staples) that provide relatively long-term compression. Together, these short-term and long-term compression mechanisms can promote tissue healing.

[0148] Generally, the mechanical properties of the bioabsorbable auxiliary material change (e.g., decrease) over time as the extent of degradation of the auxiliary material increases. In one embodiment, the auxiliary material 3020 can be configured to degrade at a rate that maintains sufficient compression (e.g., by the expanded second portion 3004′) to allow the body to coagulate / clot bleeding in the area of ​​the cut line 3022. The compressive pressure provided by the staples can be provided for a longer period of time and to a lower degree than that provided by the auxiliary material to further reinforce the cut line. Beneficially, the relatively high compressive pressure provided by the auxiliary material 3020 in the short term promotes clotting, while the relatively low compressive pressure provided by the staples in the long term reinforces without restricting blood flow to the cut line 3022.

[0149] In another embodiment, a tissue thickness compensating support material 3030 is provided and is configured to function in combination with the staples 3036 to inhibit the support material 3030 from retracting and contacting the tissue 3038 after expansion. FIG. 15 is a schematic diagram illustrating a side cross-sectional view of a stapling assembly 3040 in a pre-fired configuration, the stapling assembly 3040 including a first jaw having an anvil 3042 (partially shown) opposite a staple cartridge 3044 that houses a plurality of staples (only one staple 3036 is shown). The support material 3020 includes one or more first portions 3032 positioned on the anvil 3042 and underlying one or more second portions 3034. The first portions 3032 contact the anvil 3042, and the second portions 3034 are spaced from the anvil 3042 and face the tissue. The support material 3030 has a total initial thickness s in this pre-fired configuration. oAs shown, the first portion 3032 and the second portion 3034 are generally planar. However, other non-planar configurations may be used without limitation. Additionally, while the embodiment of FIG. 15 shows the support material positioned on the anvil, in alternative embodiments, the support material may be positioned on the staple cartridge.

[0150] 16 , tissue 3038 is clamped between the anvil 3042 and the staple cartridge 3044 and one or more staples 3036 are fired from the staple cartridge, through the support material 3030, and into the tissue 3038, thereby stapling the support material 3030 to the tissue 3038. As further shown in FIG. 17 , the support material 3030 and tissue 3038 are then released from the stapling assembly 3040 after the firing of the staples. The total thickness of the support material 3030 after release from the stapling assembly 3040 is reduced from its initial thickness s due to the removal of the clamping force applied by the stapling assembly 3040. o to an implanted thickness s1. The tissue 3038 has a thickness t1.

[0151] After being stapled to the tissue 3038, the support material 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 certain embodiments, the first portion 3032 can be formed of a moisture-absorbing, swellable polymer. The second portion 3034 can be formed of a semi-porous film. 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 can 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 can further overlap the first portion 3032 and can be mechanically coupled to the first portion 3032 (e.g., by a biocompatible adhesive or other fixation mechanism). Because the second portion 3034 is semi-porous, some of the water and / or other physiological fluids received and not absorbed by the second portion 3034 can flow through the second portion 3034 (e.g., via the open porosity) to be received by the first portion 3032.

[0152] 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 applies a second pressure to the tissue 3038. As a result of the expansion of the auxiliary material 3030 and the auxiliary material 3030 applying pressure to the tissue 3038, the thickness of the auxiliary material increases to a third thickness s2 and the thickness t-2 of the tissue 3038 decreases, as shown in FIG. 17 . In alternative embodiments, the second portion does not substantially expand or expands to a degree significantly less than that of the first portion when it receives water and / or other physiological fluids.

[0153] In other embodiments, the staple 3036 can include one or more features 3046 configured to allow expansion of the support material 3030 in a first direction (e.g., toward the tissue 3038) and inhibit retraction of the support material 3030 in a second direction opposite the first direction (e.g., away from the tissue 3038). As shown in FIGS. 16 and 17 , the one or more features 3046 can include a plurality of barbs extending along one or more of the legs of the staple 3036. The plurality of barbs are positioned such that after being fired into the support material, the barbs extend toward the base of the staple, opposite the direction of insertion of the staple into the tissue 3038. When the support material 3030 expands (e.g., due to expansion of the first portion 3032 and / or the second portion 3034), the plurality of barbs engage at least the second portion 3034. Because the second portion 3034 is mechanically coupled to the first portion 3032, engagement of the barbs with the second portion 3034 creates a ratchet-like effect that inhibits retraction of the auxiliary material 3030 away from the tissue 3038 after expansion of the auxiliary material 3030.

[0154] Embodiments of any portion of any of the support materials 3000, 3020, 3030 may be configured to exhibit a color change in response to expansion. As an example, the portion of the support material 3000, 3020, 3030 that exhibits a color change may include a color-transition dye. Examples of color-transition dyes may include hydrochromic inks configured to change color in response to at least one fluid, such as water and lipids. In further embodiments, the expandable portion of the support material 3030, 3020, 3030 formed from a water- or lipid-sensitive polymer may be in a thin, dry state when undeployed and expand to a higher state when deployed and hydrated.

[0155] The ability of selected portions of the support material 3000, 3020, 3030 to exhibit a color change upon expansion can allow for quick visual identification of expansion behavior, which can be beneficial in confirming that selected portions of the support material 3000, 3020, 3030 are in fact expanding and therefore achieving the function enabled by the expansion, such as sealing staples or applying pressure to a cut line, without the need for time-consuming measurements.

[0156] It can be appreciated that such visual identification of expansion of the portions of the auxiliary material 3000, 3020, 3030 can be used to seal staples. It can be appreciated that because the mass of the portions of the auxiliary material 3000, 3020, 3020 that exhibit a color change remains constant, the increase in volume resulting from expansion reduces the density of these portions.

[0157] Composite support materials that degrade via multiple different mechanisms As described above, it may be desirable to use a support material that exhibits compressive properties that degrade in response to the healing process in order to correlate the amount of compression applied to the tissue with the optimal amount of compression to promote tissue healing. In one aspect, degradation can be correlated to the healing process by using a support material that degrades in response to a reaction with at least one physiological element released from the tissue during the healing process. In one example, physiological elements, including reactive oxygen species, can promote degradation by participating in an oxidative reaction with the support material. In another example, enzymes released during the healing process can catalyze a hydrolysis reaction, increasing the degradation rate of the support material through hydrolysis. This concept can also be used in connection with composite support materials formed of two or more polymers, each of which degrades via a different mechanism. In this way, the degradation rate of the support material and the associated changes in mechanical properties can be controlled via two mechanisms rather than a single mechanism, providing greater functionality.

[0158] 18 is a schematic diagram illustrating a side cross-sectional view of a stapling assembly 3050 in a pre-fired configuration including a first jaw having an anvil 3052 opposite a staple cartridge 3054 that houses a plurality of staples 3056. As shown, an exemplary embodiment of a composite support material 3060 is releasably retained on the anvil 3052 and has a thickness SO. In an alternative embodiment (not shown), the composite support material 3060 can be releasably retained on either or both of the staple cartridge or the anvil for delivery to tissue by deployment of the staples in the staple cartridge.

[0159] The composite support material 3060 is shown in more detail in FIG. 19 . The composite support material 3060 is formed as a porous polymer body 3062 including a first polymer 3064 and a second polymer 3066. The first polymer 3064 overlies the second polymer 3066, which is compressed underneath the first polymer 3064. While a first polymer 3064 and a second polymer 3066 are shown, the support material may include any number of polymers. In certain embodiments, the first polymer 3064 carries at least one first drug 3070 therein. In certain embodiments, the at least one first drug 3070 is a hemostatic agent. In further embodiments, the second polymer 3066 carries at least one second drug 3074 therein configured to promote tissue remodeling. The compressive response of first polymer 3064 and second polymer 3066 and the corresponding amounts of released first drug 3070 and second drug 3074 are illustrated in Figures 24B and 24C, respectively, and are discussed in more detail below. The healing mechanism that occurs as a function of time is further illustrated in Figure 24A.

[0160] The first polymer 3064 can be configured to degrade according to a first degradation profile in response to at least one of hydrolysis and heating to physiological temperatures in response to interaction with water 3072. The first polymer 3064 can further be configured to expand in response to absorption of water 3072 and / or other physiological fluids. Examples of the first polymer 3064 include at least one of a hygroscopic powder and a hygroscopic foam.

[0161] The second polymer 3066 can be configured to degrade according to a second degradation profile in response to at least one of oxidation, enzyme-catalyzed hydrolysis, and changes in pH resulting from interaction with at least one physiological element 3076 released from the tissue during the tissue healing process, as described in more detail below ( FIG. 23 ). The second polymer 3066 is further configured to swell in response to the degradation of the first polymer 3064.

[0162] 19 and 21 , the first polymer 3064 overlaps the second polymer 3064, thus mechanically constraining the second polymer 3064. As a result, during the first time window A, the compressive pressure exerted by the second polymer 3064 on the tissue 3068 ( FIG. 24B ) is relatively low and increases relatively slowly compared to the first polymer 3064. The relatively slow rate of increase in compressive pressure can be attributed to the moderate degradation of the first polymer 3064 and the concomitant relaxation of the constraint of the second polymer 3064.

[0163] An example of the second polymer 3066 includes a porous structure. An example of the at least one physiological element may include, but is not limited to, reactive oxygen species. The reactive oxygen species may include at least one of oxygen-containing enzymes, free radicals, superoxides, and peroxides.

[0164] In certain embodiments, the second polymer 3064 holds a second drug 3074 therein. Examples of the at least one second drug 3074 may include, but are not limited to, a drug configured to promote tissue remodeling. As shown in FIG. 24C, during pre-launch (condition time window A), none of the at least one second drug 3074 is released.

[0165] In certain embodiments, the at least one second drug 3074 can be configured for at least one of bolus release or sustained release. In one example, as shown in FIG. 21 , the second drug 3074 can be encapsulated by a material 3074a configured for sustained 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, sustained release can be provided by one or more relatively large reservoirs formed within the second polymer, the reservoirs configured to provide for release of a relatively small amount of the second drug therefrom over a relatively short period of time during degradation of the second polymer. As an example, a fluid restriction device (e.g., a valve) can be used in combination with a relatively large reservoir for sustained release. In other embodiments, sustained release may be provided by multiple, relatively smaller volume reservoirs configured to independently release relatively small amounts of the second drug over time via degradation of the second polymer (e.g., release of the second drug into respective fluid passages that are not in fluid communication with each other).

[0166] In further embodiments, the bolus release of the second drug may be provided by one or more relatively large reservoirs formed within the second polymer, which reservoirs are configured to provide for the release of relatively large amounts of the second drug during degradation of the second polymer. In alternative embodiments, the bolus containment may be provided by multiple smaller reservoirs, which reservoirs are configured to simultaneously combine respective amounts of the second drug released therefrom (e.g., release of the second drug into one or more common fluid pathways) over a relatively short period of time during degradation of the second polymer.

[0167] Figure 20 is a schematic diagram showing the support material 3060 immediately after firing staples 3056 through the support material 3060 and tissue 3068 (time window B, Figure 24A). Figure 21 is a schematic diagram showing the support material 3060 in greater detail. As shown, the first polymer 3064 expands in response to interacting with water 3072. As a result of this expansion, the first polymer 3064 exerts a first compressive pressure 3080 on the tissue 3068.

[0168] The first degradation profile of the first polymer 3064 during time window B (FIG. 24A) is in response to an interaction (e.g., chemical reaction) with water 3072 (hydrolysis). This configuration may be beneficial to hemostasis because it results in a first degradation profile that exhibits a relatively rapid rate of decrease from a peak value of the first compressive pressure 3080. Thus, in certain 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.

[0169] Concurrently, the release rate 3086 of the first drug 3070 also exhibits a relatively rapid decrease, declining from a maximum value upon degradation of the first polymer 3064. That is, the at least one first drug 3070 is configured for relatively rapid release. As discussed above, the at least one first agent 3070 can be a hemostatic agent. Thus, the rapid release of the at least one first drug 3070 can further promote rapid hemostasis.

[0170] By compressing the second polymer 3066 beneath the first polymer 3064, the first polymer 3064 can restrain the expansion of the second polymer 3066. This is reflected in FIG. 24B as a relatively slow rate of increase in the second compressive pressure 3082. However, the ability of the first polymer 3064 to constrain the second polymer 3066 decreases with continued degradation of the first polymer 3064, and the rate of increase in the second compressive stress 2412 on the tissue 3068 increases as time progresses within the second time window B. As a result, the thickness of the support material 3060 can increase from an initial thickness S0 to a first thickness S1. The tissue thickness increases from the initial thickness t tissue1 The combination of first compressive pressure 3080 and second compressive pressure 3082 further promotes hemostasis and provides a restricted blood flow region 3069 for clotting.

[0171] In certain embodiments, at least one of the first polymer and the second polymer may comprise a hydrogel, which is configured to expand to a greater extent than the surrounding polymeric material. In this manner, the resulting composite support material may exhibit varying amounts of expansion. In this manner, the support material may apply different levels of compression to different areas of the tissue (e.g., cut lines, staple lines, etc.). As shown in FIG. 20 , the composite support material 3060 applies two different levels of compression C1 and C2 in different areas. For example, compression C2 is greater than compression C1 and may be positioned closer to the cut line, thereby increasing localized pressure and sealing the area until healing.

[0172] As healing progresses during second time window B (e.g., inflammation stage and release of neutrophils), the concentration of at least one physiological element 3076 received in composite supplemental material 3060 increases. As an example, neutrophils may be released along with corresponding ones of at least one physiological element 3076. Simultaneously, degradation of first polymer 3064 progresses over time, reducing the ability of first polymer 3064 to inhibit the interaction of second polymer 3066 with at least one physiological element 3076. Thus, as time progresses within second time window B, the degradation rate of second polymer 3066 increases, reflected as an increasing release rate 2086 of at least one second drug 3074 from second polymer 3066.

[0173] FIG. 22 is a schematic diagram showing the auxiliary material 3060 at a predetermined time (time window B, FIG. 24C) after firing staples 3056 through the auxiliary material 3060 and tissue 3068. FIG. 23 is a schematic diagram showing the auxiliary material 3060 in greater detail. As shown, degradation of the first polymer 3064 is substantially complete due to the relatively low first compression pressure 3080 and the relatively low release rate 3084 of the at least one first drug 3070. That is, substantially all of the at least one first drug 3070 has been released. Furthermore, with the reduction in first compression pressure 3080, the thickness of the auxiliary material 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 tissue1 to the second tissue thickness t tissue2 Advantageously, the combined first compressive pressure 3080 and second compressive pressure 3082 applied to tissue 3068 is at a level sufficient to allow for neovascularization.

[0174] Concurrently, healing continues to progress from the inflammatory phase to the proliferation and maturation phases, resulting in the release of macrophages, fibroblasts, and lymphocytes, as well as corresponding ones of at least one physiological element 3076, as shown in FIG. 24A. The advanced degradation of first polymer 3064 during time window C significantly reduces the ability of at least one first polymer 3064 to inhibit the interaction between second polymer 3066 and at least one physiological element 3076. Thus, at least one physiological element 3076 can freely flow into the pores of second polymer 3066. This increases the degradation rate of second polymer 3066 and decreases second compressive pressure 3082.

[0175] The release rate 3086 of the at least one second drug increases to a peak as degradation of the second polymer 3066 increases, then decreases from the peak. The relatively slow release of the at least one second drug 3074 can promote tissue remodeling. Examples of drugs configured to promote tissue remodeling may include drugs configured 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. Patent Nos. 10,939,911 and 10,569,071, and U.S. Patent Application Publication Nos. 2018 / 0353659, 2018 / 0353175, and 2018 / 0353174, each of which is incorporated by reference in its entirety.

[0176] Those skilled in the art will recognize that the present invention has application in conventional minimally invasive and open surgical instrumentation, as well as in robotic-assisted surgery.

[0177] The devices disclosed herein can be designed to be disposed of after a single use, or they can be designed to be used multiple times. In either case, however, the device can be reconditioned for reuse after at least one use. Reconditioning can include any combination of the steps of disassembly of the device, followed by cleaning or replacement of particular parts, and subsequent reassembly. Specifically, the device can be disassembled, and any number of particular parts or portions of the device can be selectively replaced or removed in any combination. Following cleaning and / or replacement of particular parts, the device can be reassembled for subsequent use either at a reconditioning facility or by a surgical team immediately prior to a surgical procedure. Those skilled in the art will appreciate that reconditioning of a device can utilize a variety of techniques for disassembly, cleaning / replacement, and reassembly. The use of such techniques, and the resulting reconditioned device, are all within the scope of the present application.

[0178] Those skilled in the art will recognize further features and advantages of the present invention based on the above-described embodiments. Accordingly, the present invention is not to be limited by what has been particularly shown and described, except as indicated by the appended claims. All publications and references cited herein are expressly incorporated herein by reference in their entirety.

[0179] [Embodiment] (1) A compressible aid for use with a staple cartridge, said compressible aid comprising: A biocompatible auxiliary material configured to be releasably retained on a staple cartridge body and delivered to tissue by deployment of staples in the staple cartridge body, the auxiliary material comprising a porous polymer body configured to exhibit a first stiffness in compression that is substantially constant during a first period of time from contact with the tissue and a second stiffness in compression during a second period of time following the first period, the second stiffness being less than the first stiffness and configured to decrease over time in response to at least one of oxidation, enzyme-catalyzed hydrolysis, and changes in pH resulting from interaction with at least one physiological element released from the tissue during the healing process of the tissue. (2) The auxiliary material described in embodiment 1, wherein the auxiliary material is configured to adopt the second rigidity in response to oxidation resulting from reaction with the at least one physiological element, including reactive oxygen species. (3) The auxiliary material described in embodiment 1, wherein the auxiliary material is configured to oxidize in response to a reaction with the at least one physiological element, including reactive oxygen species released by at least one of mature blood cells, fibrocytes, and inflammatory cells. (4) The aid described in embodiment 3, wherein the inflammatory cells are at least one of leukocytes and macrophages. (5) The supplement according to embodiment 2, wherein the reactive oxygen species is at least one of an oxygen-containing enzyme, a free radical, a superoxide, and a peroxide.

[0180] (6) The reactive oxygen species is O 2- , H2O2, NO, and HOCl. (7) The auxiliary material of embodiment 1, wherein the auxiliary material is configured to adopt the second stiffness in response to enzyme-catalyzed hydrolysis. (8) The supplement described in embodiment 7, wherein the enzyme comprises lysozyme. (9) The auxiliary material described in embodiment 1, wherein the auxiliary material is configured to adopt the second rigidity in response to a decrease in pH due to the presence of the at least one physiological element.

Claims

1. 1. A compressible aid for use with a staple cartridge, said compressible aid comprising: A biocompatible auxiliary material configured to be releasably retained on a staple cartridge body and delivered to tissue by deployment of staples in the staple cartridge body, the auxiliary material comprising a porous polymer body configured to exhibit a first compressive stiffness that is substantially constant during a first period of time from contact with the tissue, and a second compressive stiffness during a second period of time following the first period, the second stiffness being less than the first stiffness and configured to decrease over time in response to at least one of oxidation, enzyme-catalyzed hydrolysis, and changes in pH resulting from interaction with at least one physiological element released from the tissue during the healing process of the tissue.

2. The auxiliary material of claim 1, wherein the auxiliary material is configured to adopt the second rigidity in response to oxidation resulting from reaction with the at least one physiological element, including reactive oxygen species.

3. The auxiliary material of claim 1, wherein the auxiliary material is configured to oxidize in response to a reaction with the at least one physiological element, including reactive oxygen species released by at least one of mature blood cells, fibrocytes, and inflammatory cells.

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

5. The supplement of claim 2 , wherein the reactive oxygen species is at least one of an oxygen-containing enzyme, a free radical, a superoxide, and a peroxide.

6. The reactive oxygen species is O ２－ , H ２ O ２ 3. The auxiliary material of claim 2, which is at least one of NO, and HOCl.

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

8. The supplement according to claim 7, wherein the enzyme comprises lysozyme.

9. The auxiliary material of claim 1 , wherein the auxiliary material is configured to adopt the second stiffness in response to a decrease in pH due to the presence of the at least one physiological element.

Images