Improved Fiber Grafts

Abstract

A tubular or non-tubular fiber-based implant or prosthesis product requires two materials, a fiber and an impermeable, non-organic, hydrophobic or superhydrophobic material, to construct the implant product of the present invention, forming three distinct zones. The resulting self-sealing implant or prosthesis product is superhydrophobic, thus facilitating removal from the body. Removal is further improved by resistance of one surface to electrosurgical energy, such as electrocautery. The implant or prosthesis product not only prevents transmural communication or migration through the implant body or wall, but also allows tissue growth along at least a portion of one surface of the implant or prosthesis to achieve secure fixation.

Description

[Technical field]

[0001] [Inventor] Aaron Hjelle, Andover, Minnesota, American citizen. Robert Thatcher, Blaine, Minnesota, American citizen. Brian McMurray, Pine Bluff, North Carolina, American citizen. Stephanie B. Norris, Rocky Point, North Carolina, American citizen. Joseph M. Shepley, Wernersville, Pennsylvania, American citizen. Savannah R. Forrester, Mauldin, South Carolina, American citizen. Lindsey Sanders Calcutt, Greenville, South Carolina, US citizen. [CROSS REFERENCE TO RELATED APPLICATIONS] This application claims the benefit of U.S. Provisional Application No. 63 / 362,082, filed March 29, 2022, and entitled "TEXTILE GRAFTS," the entire contents of which are incorporated herein by reference. [STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT] N / A

[0002] [Background of the invention] [Field of the Invention] The present invention relates generally to textile products, and more particularly to a fiber-based graft that is stably fixed after implantation, does not allow transmural communication or migration through the graft, and has improved water repellency on one surface to prevent incorporation into the body and allow for easy removal. [Background technology]

[0003] [Description of Related Art] The present technology generally describes layered grafts with fibers, focusing on self-sealing vascular grafts that aid in repeated punctures in AV grafts in dialysis patients. Some known layered grafts have one surface covered with a semi-permeable, non-porous, water-insoluble sealing material with limited water repellency, and generally have a removable masking material or coating on the opposite surface, such as the luminal surface of a tubular graft, in the initial state, and the interstices and / or pores of the fibers are provided with a removable masking material or coating to prevent the penetration or migration of water-insoluble materials through the fibers and ultimately the ingrowth of tissue necessary for the stability of the graft.

[0004] Some known implants have three layers of material with a self-sealing material sandwiched between an inner and outer layer, such as the Triplex® implant commercialized by Vascutek Terumo. TМ The vascular graft comprises an inner layer of uncoated Dacron fabric and an outer layer of expanded polytetrafluoroethylene (ePTFE). The two layers are fused together by a middle or central layer of a self-sealing elastomeric membrane that is the thermoplastic elastomer styrene-ethylene-propylene-styrene (organic (styrene) copolymer). Triplex TМ The leakage value of the graft was 0.68 mL / cm 2 / min, which indicates good but not complete impermeability to water (or blood). See De Paulis, et. al., A Third Generation of Ascending Aorta Dacron Graft: Preliminary Experience, Ann Thorac Surg 2008; 85:305-09. De Paulis et al. state that the three-layer construction provides complete impermeability. However, the leakage value reported by De Paulis et al. is not 0, but 0.68 mL / cm 2 / min. Therefore, the triplex TМ The three-layer structure cannot be said to be impermeable.

[0005] An improved version of the typical three-layer vascular graft is the two-layer vascular graft (trade name: Biplex) commercialized by Vascutek Terumo. TМ ) which has an inner uncoated polyester woven layer and an outer tubular surface coated with an intermediate Triplex TМ The self-sealing elastomer is coated with the same thermoplastic elastomeric styrene copolymer used in the Triplex layer. TМ For the same reasons as mentioned above for the structure and associated non-zero leakage values, TМ Nor can it be said to be completely impermeable to water or blood.

[0006] Furthermore, none of the above-mentioned Vascutek Terumo vascular graft products can be described as "non-porous." In other words, Biplex TМ and Triplex TМ all allow for the transmural migration of cells and other materials from one side of the graft wall to the other after implantation. Transmural communication is generally considered a requirement for effective long-term implants, such as vascular grafts, and allows for tissue ingrowth on both sides of the graft, e.g., both the luminal and abluminal surfaces of exemplary vascular or tubular grafts, resulting in internalization of the graft by the host tissue.

[0007] The high degree of endothelialization of the implant results in fixation stability, but makes it very difficult to extract the implant from the endogenous tissue. An electrocautery is usually required both to actually visualize the implant and to separate it from the surrounding tissue. Known implants fail to provide an outer layer that is impervious to the electrocautery or that does not allow the energy of the electrocautery to penetrate the outer layer of the implant and damage the fibrous layer. Summary of the Invention

[0008] Accordingly, one object of the present invention is to provide an implant having surfaces and / or layers that are impervious to energy applied to the implant by an electrosurgical device, for example, but not limited to, electrocautery energy.

[0009] Another object of the present invention is to provide an implant with a sealing layer that protects the underlying fabric layer from exposure to and / or damage caused by electrocautery energy.

[0010] It is another object of the present invention to provide an implant with a sealing layer that minimizes or reduces damage to the underlying fibrous layer from electrocautery energy.

[0011] Another object of the present invention is to provide an implant with a sealing layer that minimizes, mitigates, or prevents damage to the underlying fibrous layer from low, medium, or high power electrocautery energy.

[0012] Another object of the present invention is to provide a method for producing a 0.68 mL / cm 2 / min to 0 mL / cm 2 The object of the present invention is to provide an implant having a water leakage value or water permeability in the range of 0.16 mL / cm under a pressure of 120 mmHg. 2 Most preferably, the water leakage value, or water permeability, is substantially 0 mL / cm under a pressure of 120 mmHg. 2 / min.

[0013] Another object of the present invention is to prevent transmural communication or migration of cells or substances from one side or surface of the graft to and / or through the other side or surface of the graft.

[0014] Another object of the present invention is to provide maximum and complete prevention of incorporation on the sealant side of an implanted graft or surface of an implant structure.

[0015] Another object of the present invention is to enable or promote partial incorporation of an implanted graft into the body, the incorporated portion being easily accessed and separated from body tissue.

[0016] Another object of the present invention is to allow adhesion and activate tissue ingrowth of living tissue and / or platelets on at least a portion of one side or surface of the implant, while completely preventing adhesion or ingrowth of living tissue and / or platelets on the other side or opposing surface of the implant.

[0017] Another object of the present invention is to allow adhesion and stimulate tissue ingrowth of living tissue and / or platelets on at least a portion of one side or surface of the implant, while promoting or allowing adhesion or ingrowth of living tissue and / or platelets on only selected portions of the other side or opposing surface of the implant.

[0018] Furthermore, the outer coatings of known vascular grafts typically comprise organic polymers having carbon-carbon bonds with bond energies of 355 kJ / mol, and as a result, these organic polymer outer layers offer only limited resistance to the electrocautery procedures typically required during removal of implanted grafts.

[0019] It is therefore another object of the present invention to provide a sealing layer and surface for an implant that is more resistant to electrocautery than sealing layers formed from known organic polymeric materials.

[0020] Another object is to provide a sealing layer that inhibits, retards, and / or minimizes penetration and / or damage during electrocautery procedures at all power and voltage levels.

[0021] Another object is to provide a sealing layer that prevents penetration and / or damage to the underlying fabric layer during electrocautery procedures at all power and voltage levels.

[0022] Yet another object is to provide a sealing layer that protects the underlying fabric layer by inhibiting, slowing and / or minimizing the penetration of electrocautery energy through the sealing layer at all power and voltage levels.

[0023] Another object is to provide an outer sealing layer that is impervious to electrocautery at all power and voltage levels.

[0024] Another object of the present invention is to provide an outer sealing layer having a smooth outer or exterior surface, either completely or partially, to inhibit adhesion of living tissue and / or platelets.

[0025] It is yet another object of the present invention to provide an outer sealing layer which prevents bacterial adhesion and the development of infection between the outer sealing layer and the host tissue.

[0026] It is also an object of the present invention to prevent and / or inhibit the formation of seroma between the sealant and the host tissue.

[0027] Another object of the present invention is to incorporate an antibiotic material or compound onto or within the outer sealing layer.

[0028] Also, known vascular grafts are difficult to visualize during implantation and harvesting procedures when blood is present. Therefore, it is a further object of the present invention to provide an outer sealing layer of the graft, or one of its surfaces, that changes from hydrophobic to superhydrophobic and / or from hydrophobic to superhydrophobic. In this manner, blood is excluded from the outer sealing layer of the embodiments according to the present invention, making it easier for the practitioner to view the implanted device.

[0029] Another object of the present invention is to provide certain embodiments with a colorant along a portion of the outer sealing layer, which has a contrasting color to blood and tissue.

[0030] As mentioned above, known layered grafts require the application of a removable mask or coating on the exemplary luminal surface of the fibers of the tubular graft to prevent the sealant from migrating through the fiber layer to reach the luminal surface. This prevents tissue ingrowth on that surface, reducing fixation stability during implantation. This approach reduces the thickness of the finished sealing layer, reducing the stiffness of the implanted product and increasing its flexibility. It also requires the use of a removable mask that effectively blocks the migration of the sealant, such that at least a portion of the luminal surface is not covered with the sealant, and sufficient sealant remains on the opposite or outer surface to provide the required protective function.

[0031] All known layered grafts that use a removable mask or coating to protect a surface of the graft, such as the inner or luminal surface, from migration of the sealant require placing the removable mask or coating on the luminal surface, such as the vascular graft, and then removing the mask or coating to expose the underlying fibers free of the sealant. This configuration allows the sealant to migrate substantially through the inner or fibrous layer, thereby leaving a relatively small distance unaffected by the sealant as a result of the protection provided by the masking or coating. This reduces the width or thickness of the inner or fibrous layer available for tissue ingrowth.

[0032] It is therefore another object of the invention to reserve most of the thickness of the inner or fibrous layer for tissue ingrowth.

[0033] Known layered implants also require that a mask or coating applied to the luminal surface be removed, either actively, for example by etching, or passively, for example by water solubility, prior to implantation.

[0034] The present invention specifically addresses these problems.

[0035] A fiber-based graft product requires two materials: a fiber and a sealant. In some embodiments, the sealant is an impermeable, non-organic hydrophobic or superhydrophobic material that, when incorporated into the graft product of the present invention, creates three distinct cross-sectional zones. The resulting self-sealing graft product is superhydrophobic, facilitating removal from the body. Removal is further improved by the resistance of the sealant to electrocautery. The graft product not only prevents transmural communication or migration through the graft body or wall, but also prevents blood leakage while allowing tissue ingrowth along at least one surface of the graft for secure fixation within the body. [Brief description of the drawings]

[0036] Embodiments of the invention will now be described, by way of example only, with reference to the drawings in which: FIG. [Figure 1A] FIG. 1A shows an end perspective view of one embodiment of the present invention. [Figure 1B] FIG. 1B shows an end perspective view of one embodiment of the present invention. [Diagram 2] FIG. 2 shows an end or cross-sectional view of one embodiment of the present invention. [Figure 3A] FIG. 3A shows a cross-sectional view of one embodiment of the present invention. [Figure 3B] FIG. 3B shows a side view of one embodiment of the present invention. [Figure 3C] FIG. 3C shows a side view of one embodiment of the present invention. [Figure 4A] FIG. 4A shows a perspective view of one embodiment of the present invention. [Figure 4B] FIG. 4B shows a perspective view of one embodiment of the present invention. [Figure 4C] FIG. 4C shows a perspective view of one embodiment of the present invention. [Figure 4D] FIG. 4D shows a perspective view of one embodiment of the present invention. [Diagram 5]FIG. 5 shows a top view of one embodiment of the present invention. [Figure 6] FIG. 6 shows a perspective view of one embodiment of the present invention. [Figure 7] FIG. 7 shows a cross-sectional view of one embodiment of the present invention. [Figure 8] FIG. 8 shows a side cross-sectional view of one embodiment of the present invention. [Figure 9] FIG. 9 shows a side cross-sectional view of one embodiment of the present invention. [Figure 10] FIG. 10 shows a top view of one embodiment of the present invention. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0037] In general, various embodiments of the present invention are directed to devices and methods for prostheses or implants, e.g., grafts, sheets, tapes, and / or patches, such as vascular grafts, that may include conduits or tubular portions. Exemplary grafts may be cylindrical as well as several other functional shapes described herein. However, various embodiments are directed to non-tubular and / or non-conduit structures, e.g., flexible sheets, planar structures, tapes, or preformed structures, that may be flat or contoured and are suitable for covering non-tubular structures. Such non-tubular grafts may be used as patches, for organ repair, for pericardial surgery, and the like, as will be appreciated by those skilled in the art. The embodiments of prostheses or implants, e.g., grafts or patches, described herein may further include fabrics, fibers, or threads, and may include fibers that are woven and / or knitted or otherwise combined in a pattern or patterns to form a fiber. Other configurations and materials for such fibers are known in the art and are therefore within the scope of the present invention. In general, the following description will be described as specific embodiments of prostheses or implants, e.g., grafts. However, as will now become apparent, this is not a limiting description, as the prosthesis and / or implant of the present invention includes all other embodiments described herein.

[0038] DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS The present invention is directed to making the surgical removal of an exemplary prosthesis or implant, e.g., a graft, from a living body a simpler process. In general, an outer or first sealing layer is provided that is not damaged by energy applied, e.g., by an electrocautery. In other embodiments, the outer or first sealing layer prevents the energy of an exemplary electrocautery from penetrating through the outer or first sealing layer to the inner or second fabric layer, thereby preventing damage to the inner or second fabric layer.

[0039] Additionally, the outer or first sealing surface may be hydrophobic or may be superhydrophobic and / or superhydrophobic, since the outer or first sealing layer may exclude blood for ease of visualization during extraction or removal. In some embodiments, the outer or first sealing layer is non-porous and has a surface roughness that aids in preventing adhesion of biological tissue and / or platelets, while the inner lumen or second opposing fiber surface allows biological tissue and / or platelets to adhere thereto.

[0040] In some embodiments, the outer or first sealing layer may be constructed with a color that contrasts with blood and tissue to aid in visualization during extraction or removal.

[0041] In some embodiments, the implant may have substantially zero water leakage or water permeability, primarily due to the impermeability of the outer, or first, sealing layer.

[0042] In some embodiments, the first or outer sealing surface prevents ingrowth of biological tissue into any portion of the first or outer sealing surface, while at least a portion of the lumen, i.e., the second opposing fiber surface, allows biological tissue and / or platelets to adhere thereto and adhere to at least a portion of the lumen, i.e., the second opposing fiber layer, to provide fixation stability within the body.

[0043] In some embodiments, transmural migration of biological material or water from one side of the wall of the exemplary implant to the other is prevented.

[0044] In some embodiments, the first or outer sealing surface prevents bacterial adhesion and thereby prevents infection from occurring between the first or outer sealing surface and host tissue in contact with the first or outer sealing surface.

[0045] In some embodiments, the sealant is configured to prevent seroma formation between the first or outer surface of the sealing layer and the host tissue.

[0046] In some embodiments, an antibiotic is incorporated into, embedded in, or coated onto at least a portion of the sealing layer prior to implantation.

[0047] In some embodiments, a portion of the sealing layer is impregnated with an antibiotic.

[0048] In some embodiments, an antibiotic can be encapsulated and embedded within or on the sealing layer, the capsule being configured to be biodegradable or dissolvable.

[0049] In some embodiments, a foaming agent may be combined with the polymer or copolymer of the outer or first sealing layer to form a flexible structure that also has improved self-sealing capabilities.

[0050] In some embodiments, the suture hole may close naturally such that hemostasis is achieved within 10 minutes, 5 minutes, 2 minutes, 1 minute, 30 seconds, or 10 seconds of creating the suture hole.

[0051] In some embodiments, the dielectric polymer or dielectric copolymer may comprise an outer or first sealing layer to form an electrocautery resistant implant.

[0052] In some embodiments, the sealing layer has a radiopaque material or a plurality of radiopaque markers attached to, embedded in, impregnated with, and / or exposed within the sealing layer.

[0053] In some embodiments, two materials forming three cross-sectional zones may constitute an exemplary prosthesis or implant, e.g., a graft, where there is a first zone having only the exemplary woven (or knit) fabric, a second zone having a combination of a sealant and woven fabric having some or all of the above-mentioned properties, and a third zone having only the sealant.

[0054] In some embodiments, a three zone embodiment is achieved without the need for a removable mask or coating, realizing the first zone having only the exemplary woven or knit fabric.

[0055] In other embodiments, a removable mask or coating may be employed on the inside, or second opposing surface, of the exemplary woven or knit fabric to maintain a portion of the woven or knit fabric without contaminating the woven or knit fabric as the sealant in Zone 3 moves through the woven or knit fabric to form Zone 2.

[0056] In some embodiments, one or more structures, regions, or materials are provided on the exterior surface of the sealing layer to promote the formation of a pseudointima on the luminal surface, i.e., the second surface, of an exemplary implant or prosthesis, e.g., a graft.

[0057] In some embodiments, one or more structures, regions, or materials are provided on the exterior surface of the sealing layer to allow controlled communication of biological materials and / or cells through the sealing layer and promote tissue ingrowth on the fiber-only surface.

[0058] In some embodiments, one or more structures, regions or materials are provided on the exterior surface of the sealing layer to facilitate stabilization of at least the exterior or outer surface of the sealing layer through the incorporation of fibers and to allow controlled communication of biological material and / or cells through the sealing layer.

[0059] 1A and 1B provide perspective views of one embodiment of an exemplary tubular, ductal or vascular graft. The exemplary tubular graft 10 includes an inner fabric layer 12 having a thickness of fabric layer 12 and defining a lumen 14 and an inner or luminal surface 16. An outer sealing layer 18 surrounds the inner layer 12, defining a thickness of the sealing layer 18 and defining an outer or luminal surface 20.

[0060] The illustrated graft 10 has an inlet (I) and an outlet (O) at opposing ends. However, it is understood that in alternative embodiments, one or more inlets or outlets may be provided. Additionally, the graft may have a cylindrical shape as shown, or may have a non-cylindrical shape with one or more regions having a larger outer diameter than other regions, multiple channels, a Y-shape or T-shape, or the shape of an aortic root, for example, as may be used in a Valsalva aortic root graft.

[0061] The inner textile layer 12 may comprise textiles that may be woven, braided, or knitted, as will be readily understood by those skilled in the art, thus providing a plurality of interstices, spaces, and / or pores between the textile fibers, threads, and / or fabrics, some of which may allow for adhesion of living tissue and / or platelets after implantation, followed by tissue ingrowth, thereby anchoring and stabilizing the implanted graft. Electric scalpel resistance

[0062] Applicants have discovered that the molecular bond energy in non-organic polymers, such as silicone and silicone foam rubber, is highly advantageous in that it is virtually impermeable to energy applied by electrosurgical techniques and / or devices such as electrocautery energy. Because the molecular bond energy of organic polymers is lower, such materials are not impermeable to electrocautery energy.

[0063] As used herein, "electrocautery" refers to the well-known process in which an electric current is passed between an electrode and a cathode, and may be either monopolar or bipolar. The device may be applied to living tissue to achieve various degrees of tissue destruction. In the case of removal of an implant from a living body, tissue may overlie some or all of the implant surface. In the case of an exemplary tubular implant, an electrocautery may be required to remove the overlying tissue to allow visualization. It is critical to protect the exemplary implant from damage caused by the thermal energy of the electrocautery. The descriptions of electrocautery and ophthalmic electrocautery are merely exemplary. Various embodiments herein provide protection from any electrosurgical energy applied.

[0064] This is to be distinguished from ophthalmic electrocautery and surgery, which includes a resistive wire through which an electric current is passed. The resistive wire may be heated and used to penetrate an implant or other graft for various purposes. As a result, some embodiments of tubular or non-tubular grafts described herein allow for ophthalmic electrocautery to penetrate not only the sealing layer but also the underlying fabric layer. In this manner, embodiments of the grafts can prevent damage to the underlying fabric layer under all known power and / or voltage settings of electrocautery, and also allow the ophthalmic electrocautery device to penetrate or cut through the sealing layer, e.g., silicone, and the underlying fabric graft, as described further below. Example 1

[0065] Objective: To test the hypothesis that better resistance than organic polymer sealants can be achieved by using non-organic polymer sealants.

[0066] Materials and Methods: In this study, we used (1) Gelweave, a commercialized sealant from Acutek Terumo, which consists of a woven fabric (Dacron) coated with gelatin, an organic polymer sealant. TМ (1) a tubular graft, and (2) a woven graft coated with a silicone layer were evaluated and compared.

[0067] Both tubular grafts were soaked in 0.9% saline and then tightly wrapped in uncooked chicken to simulate the condition of the grafts after they are implanted in the body. The tissue must be incised with an electric scalpel to simulate the tissue enveloping or surrounding the graft and to expose the graft for removal and examination. The electric scalpel was a Valleylab Force FX-C. User Guide (Force FXTM-C Electrosurgical Generator (Instant Response TМ User's Guide Force FXTM-C Electrosurgical Generator with Instant ResponseTM Technology, copyright 2009, is hereby incorporated by reference in its entirety and is located at: 1023200.book (equippedmd.com), which is hereby incorporated by reference in its entirety.

[0068] Cautery parameters were set to 50% power and pure incision mode.

[0069] Discussion: Gelweave TМ The graft has been found to be highly reactive to electrocautery energy. The saline pre-soak penetrates the graft and provides a low resistance electrical path. The organic polymer gelatin (sealant) offers little or no protection to the inner fabric (Dacron), resulting in damage to the fibrous portion of the graft.

[0070] The silicone covered textile graft was found to inhibit and retard any damage to the sealing layer. In fact, the sealing layer was observed to be completely non-reactive, i.e., completely impermeable, to the energy of the electrocautery. As a result, the textile tubular layer was completely unaffected and undamaged by the electrocautery.

[0071] Conclusion: A non-organic polymeric sealant covering or surrounding a fabric layer retards or prevents damage from electrocautery energy. Under the electrocautery parameters of this example, the sealant layer is impermeable to electrocautery energy and / or protects the fabric layer from damage from electrocautery energy. Example 2

[0072] OBJECTIVE:To test the hypothesis that a non-organic polymeric sealant would protect textile grafts from electrocautery damage by surrounding or covering the textile graft and at least inhibiting and / or delaying any damage resulting from electrocautery energy.

[0073] Materials and Methods: In this study, a woven tubular graft coated with a silicone layer was evaluated, which is the same type of woven graft as described in Example 1.

[0074] The tubular graft was pre-soaked in 0.9% saline. The electric scalpel used was the same as in Example 1, Force FX-C (Valleylab).

[0075] In this series of experiments, the electrocautery device was used in both cut and coagulation modes, all in monopolar mode, at increasing power levels. result

[0076] [Table 1]

[0077] [Table 2]

[0078] Additionally, in Example 2, saline was placed within the tubular graft and clamped at both ends to hold the saline therein during electrocautery testing. The temperature of the saline was measured before and after electrocautery testing. The temperature of the saline within the graft showed little increase after electrocautery testing, and therefore the saline within the graft was not affected by the heat increase caused by the electrocautery testing process.

[0079] Thus, non-organic polymeric sealants, such as silicones, are excellent thermal and electrical insulators. These properties allow the sealing layer to function in minimizing and / or mitigating thermal and / or electrical conduction to and / or through the underlying fiber layer. Providing protection against thermal conduction is important. Blood passing through the graft is protected from thermal damage, such as hemolysis. Additionally, tissue grown on at least a portion of the fiber layer and / or sealing layer is protected from thermal damage. Also, during certain surgeries, blood flow may be temporarily stopped, i.e., quiescent, within the graft, making blood cells within the graft, particularly those blood cells closest to the luminal surface of the fiber layer, more susceptible to thermal damage. Additionally, the grafts of the present invention may include therapeutic cells and / or associated therapeutic drugs and / or antibiotics or other substances attached or incorporated into the graft. The sealing layer described herein protects blood cells and endogenous tissue, as well as therapeutic cells and associated therapeutic drugs and / or antibiotics or other substances attached or incorporated into the graft, from thermal conduction and resulting thermal damage.

[0080] In each of Examples 1 and 2, silicone is also a strong dielectric, thus blocking the path to ground and providing additional resistance to electrocautery. Overall conclusions: Examples 1 and 2

[0081] The implant described above therefore comprises a sealing layer.

[0082] (1) Protects the underlying fibrous layer from damage caused by the electrocautery energy of the tested device at all power levels tested (including the highest power level) and when configured in both cut and coagulation modes.

[0083] (2) delaying, inhibiting, minimizing, or at least partially mitigating damage to the sealing layer itself;

[0084] (3) delay, inhibit, minimize, or at least partially reduce damage to the underlying fibrous layer by electrocautery energy in both cutting and coagulation modes at all power levels tested, including the highest power level;

[0085] (4) provide at least some protection to underlying fibers from damage by electrocautery energy in both cutting and coagulation modes at all power levels tested, including the highest power level;

[0086] (5) Provide protection against complete or partial penetration and / or penetration of the underlying fiber layers by electrocautery energy at all power levels tested, including the highest power level;

[0087] (6) delay, inhibit, protect, and / or do not damage the electrocautery energy in both the cutting and coagulation modes at all power levels tested, including the highest power level;

[0088] (7) Located within the fabric layer and / or on the side of the graft opposite the sealing layer receiving energy from the electrocautery procedure, to provide thermal resistance and / or thermal protection to blood cells, endogenous tissue, therapeutic cells, drugs, antibiotics, substances, fluids, tissues, etc.

[0089] These conclusions apply equally to both tubular and non-tubular grafts having non-organic polymeric sealing layers or coatings such as silicone.

[0090] Furthermore, silicone, an exemplary non-organic polymeric sealant, has a higher bond energy than carbon-carbon (C-C) bonds (433 kJ / mol vs. 355 kJ / mol) due to the siloxane bonds (-Si-O-Si-) that form the backbone of silicone (dimethylpolysiloxane). For the same reason, inorganic polymeric sealants generally have higher bond energy than organic polymeric sealants. Due to this characteristic, non-organic polymeric sealants have higher heat resistance than organic polymeric sealants. As a result, non-organic polymeric sealants are more resistant to electric scalpels than organic polymeric sealants. Silicone is a dielectric material as described above, and is an example of a non-organic polymer with the additional advantages of further increasing resistance to electric scalpels and being water-impermeable and non-porous.

[0091] 2 shows a cross-sectional view of one embodiment of the present invention, where two materials form an exemplary tubular graft 10, which has three zones composed of or formed by the two materials as shown in the cross-sectional view. Thus, an inner or fibrous layer 12 having the above-mentioned fibers is surrounded by an outer or sealing layer 18 formed from a sealing material that retards, inhibits, and / or prevents electrocautery from reaching the inner fibrous layer 12, among other things described herein. The concepts described herein apply generally to the subject prosthesis or implant.

[0092] As shown, the innermost zone 1 is comprised of only the exemplary fiber material. Zone 1 has a thickness less than the thickness of the fiber layer 12. This is due to the sealant migrating radially inward to occupy a portion of the fiber layer 12 by filling the gaps and / or pores of the fiber layer 12. As a result, zone 2 has a combination of both fiber material and sealant and has a thickness less than the thickness of the fiber layer 12. Zone 3 is comprised of only the sealant and has a thickness equal to or less than the thickness of the outer seal layer 18 due to the loss of sealant material during the migration process that forms zone 2. Thus, the nominal outer diameter of the tubular stent decreases over time as the sealant migrates inward and radially into the adjacent fiber layer 12. Alternatively, the sealant may penetrate or migrate into the exemplary fibers, effectively eliminating zone 1. In other embodiments, the sealant may penetrate at least a portion of the luminal surface 16, with other areas of the luminal surface 16 being comprised of only fibers.

[0093] Zone 1 is bounded on the luminal side by luminal surface 16 .

[0094] Zone 2 is bounded on the outside by interface L of the fibrous layer 12, at which the sealing material of the sealing layer 18 forms an interface with the fibrous layer 12, at least initially.

[0095] In Figure 2, the transition between Zone 1 and Zone 2 is shown by a dotted line, representing the end of the radially inward migration path of the sealant across interface L into fiber layer 12. As will become apparent, the inner fiber layer 12, after migration of the sealant, is partitioned into inner Zones 1 and 2, with Zone 2 at least partially surrounding Zone 1.

[0096] Planar grafts, sheet grafts, tapes, or other non-tubular shapes, as shown in Figures 3A-3C, are also within the scope of the present invention. As described herein, such non-tubular grafts can be used as patches, for organ repair, in pericardial surgery, and other procedures, as one of skill in the art will readily recognize. The exemplary planar graft 30 has a first, or sealing layer 32 formed of a sealing material that, in certain embodiments, provides impermeability to electrocautery, as described herein, and the sealing layer 32 defines a first surface 33. A second layer, or textile layer 34, is disposed adjacent the sealing layer 32 and is formed of an exemplary textile material as described herein, and the textile layer 34 defines a second surface 36. Line L' indicates the interface of the textile layer 34, and indicates at least an initial boundary between the sealing layer 32 and the textile layer 34. In an alternative embodiment, similar to the tubular graft embodiment of Figure 2, two materials, the first and second layers 32, 34, may be used to form three zones, as shown in Figure 3C.

[0097] Zone 1 is comprised solely of the exemplary fiber material.

[0098] Zone 2 is constructed from an exemplary fibrous and sealant blend.

[0099] Zone 3 consists of the seal material only.

[0100] Consistent with the embodiment of FIG. 2, zone 1 has a thickness less than the thickness of fibrous layer 34 due to the sealing material of sealing layer 32 having migrated into the fibrous material.

[0101] Zone 2 has a thickness from interface L' of fibrous layer 34 to a dotted line indicating the end of migration of the sealant into the fibrous material of fibrous layer 34 and toward second surface 36. As shown, the thicknesses of Zone 1 and Zone 2 are less than the thickness of fibrous layer 34 because fibrous layer 34 is formed from Zone 1 and Zone 2. Zone 2 is adjacent to Zone 1.

[0102] The thickness of Zone 3 may be the same as the thickness of sealing layer 32, and in some embodiments may be less than the initial thickness of sealing layer 32 when first applied to the fibrous layer due to loss of sealing material due to the migration process from sealing layer 32 to fibrous layer 34. It is highly preferred that Zone 3 is provided, i.e., not all of the sealing material migrates to Zone 2, and Zone 3 has sealing material that defines the thickness of Zone 3.

[0103] Each of the embodiments of Figures 2 and 3A-3B includes a continuous boundary between Zones 1 and 2, indicating the endpoint of migration of the sealant into the fibrous layer in each embodiment.

[0104] Among other things, this creates a strong bond between the sealing layer and the fiber layer of the exemplary tubular and non-tubular grafts 10, 30. In both embodiments, the sealing material is prevented from migrating to the luminal surface 16 in the tubular embodiment 10, and the sealing material is prevented from reaching the second surface 36 in the non-tubular embodiment 30, thereby providing unentrained fiber along the entire surface area of ​​those unentrained regions 16, 36 for tissue ingrowth after implantation.

[0105] This result may be achieved by applying a mask or coating to the entire luminal surface 16 or the entire second surface 36 of the fiber to prevent migration of the sealing material thereto, as disclosed in U.S. Patent No. 10,926,003, the contents of which are incorporated herein by reference in their entirety.

[0106] Alternatively, some of the sealing material may be allowed to reach the luminal surface 16 of a tubular embodiment, or the second surface 36 of a non-tubular embodiment. As also disclosed in U.S. Patent No. 10,926,003, this result may be achieved by selectively applying a mask or coating to the luminal surface 16 or the second surface 36, thereby preventing migration of the sealing material to selected areas of the luminal surface 16 or second surface 36 of the fiber, while selectively allowing migration of the sealing material to other areas of the luminal surface 16 or second surface 36 of the fiber.

[0107] According to U.S. Pat. No. 10,926,003, prevention of complete migration of the sealant, removable mask, or coating to the luminal surface of the tubular graft is accomplished by applying the sealant, removable mask, or coating to cover the entire luminal surface 16 of the tubular graft. U.S. Pat. No. 10,926,003 further teaches that some of the sealant may be permitted to migrate to the luminal surface of the tubular graft by placing an exemplary mandrel within the lumen of the tubular graft, the mandrel having an opening therethrough. The removable mask or coating is applied to the lumen of the mandrel, and the applied removable mask or coating is applied radially outward through the opening in the mandrel to coat the corresponding area of ​​the luminal surface 16 of the woven tube. In addition to teaching how to apply the mask or coating to the luminal surface 16, the removable mask or coating is taught as requiring an etching or similar active process, as opposed to a passive process such as dissolving, to remove the applied mask or coating.

[0108] An alternative mechanism for transferring some of the sealant to a selected portion of the luminal surface 16 of a tubular graft, or to the second surface 36 of a non-tubular graft, comprises applying a mask or coating to selected portions of the interface L or L'.

[0109] Facilitates identification and removal of limited, but effective, areas of tissue ingrowth and allows for incorporation of a sealing layer into the body

[0110] The outer surface of the sealing layer is desirably provided with a material that does not promote tissue ingrowth, however, in some embodiments, a portion or area of ​​the outer surface of the sealing layer may be configured to promote tissue ingrowth to ensure stability of the implanted implant.

[0111] Some embodiments may include at least one scrim region having fabric, fibers and / or threads, or other non-sealing materials embedded or incorporated along the outer surface of the sealing layer. In some embodiments, tissue growth promoting substances and / or antibiotics and / or immunosuppressive substances may be coated on or adhered to the scrim. Exemplary substances that may be coated on, adhered to, or seeded on the scrim are described below and include antibiotics, therapeutic cells, modulating agents, immunosuppressants, and the like.

[0112] As shown in Figures 4A-4D, and with continued reference to Figures 1A-3C, the exemplary scrim 50 may be circumferential (for tubular grafts), longitudinal, spiral, or may be applied randomly or in a pattern to cover a portion of the outer surface of the sealing layer 18 of the exemplary tubular graft 10 while providing an additional surface that does not promote tissue ingrowth. The exemplary scrim 50 may be applied to tubular or non-tubular grafts. See Figure 5 for an exemplary scrim 50 configuration in the sealing layer 32 of a non-tubular graft 30.

[0113] In general, the scrim 50 may be embedded within the sealing layer 18 or 32 so as not to significantly increase the outer diameter of the tubular or non-tubular graft 10, 30. In some of these embodiments, the scrim 50 may be applied to the interface L or L' such that the scrim and fibrous layer are in contact and the scrim is effectively surrounded by the sealant without an intervening sealant. In other embodiments, the scrim may be adhered to the outer surface of the sealing layer of the tubular or non-tubular graft 10, 30, thereby slightly increasing the outer diameter of the graft 10, 30.

[0114] Other embodiments may include fabrics, fibers, threads, and / or non-sealing materials that are knitted, woven, or otherwise constructed to cover or sleeve at least a portion of the outer sealing layer of the implanted tubular or non-tubular graft. These solutions may also include antibiotics and / or tissue growth promoters as described above. FIG. 6 illustrates an exemplary embodiment of a tubular graft 10 that includes a fabric sleeve 52 that partially covers the sealing layer 18 and is attached to and / or bonded to the sealing layer 18. The fabric sleeve 52 may be water soluble or otherwise biodegradable in some embodiments.

[0115] In some embodiments, the scrim and / or fabric, fiber, yarn and / or non-sealing material covering or sleeve may be configured with a color such as blue or other color that provides contrast against tissue and blood and aids in identifying the location of the implanted graft and the scrim and / or fabric covering or sleeve.

[0116] The scrim and / or fabric, fibers, yarns and / or covering or sleeve of non-sealing material may in some embodiments be water soluble or biodegradable.

[0117] The scrim and / or fabric, fiber, yarn and / or non-sealing material cover or sleeve may, in some embodiments, include at least a partial cover of a water soluble layer or film to at least partially protect the scrim and / or fabric cover, fiber, yarn and / or non-sealing material or sleeve and to protect and / or prevent premature loss of substances that may be coated, adhered or seeded onto the scrim and / or fabric cover, fiber, yarn and / or non-sealing material or sleeve. Additionally, such water soluble films may be used to form a time release structure or framework for exposing the scrim to blood and / or substances that may be coated, adhered or seeded onto the scrim and / or fabric, fiber, yarn and / or non-sealing material cover or sleeve. FIG. 7 provides a cross-sectional view of an exemplary tubular graft 10 having an exemplary circumferential scrim 50 embedded within or adhered to the outer sealing layer 18 and a water soluble film 60 disposed on at least the scrim 50. It should be understood that the scrim 50 may have the materials described herein coated thereon, adhered to the scrim 50, and / or seeded on or within the scrim 50. Achieving and / or maintaining self-sealing and hemostasis

[0118] Certain embodiments of prostheses, implants, such as tubular or non-tubular grafts, patches, sheets, tapes, etc., as described herein may include, but are not limited to, improvements that assist in achieving and / or maintaining hemostasis.

[0119] Continuing with reference to the figures, sealing layer 18 (tubular example) or sealing layer 32 (non-tubular example) may be comprised of a sealant formed from a polymer, copolymer, dielectric material, or organic or non-organic polymer or copolymer, any of which may be combined with a foaming agent in some embodiments to improve the self-sealing ability of the implant. The sealant of the present invention is selected to provide, among other things, one or more of impermeability to electrocautery damage, improved blood clearance, improved visibility within the body, improved resistance to adhesion of materials to the outer surface, resistance to bacterial adhesion to the outer surface of the sealant, seroma formation and / or infection between the implant surface and living tissue in contact, improved strength of self-seal after puncture, and improved water leakage or water permeability.

[0120] The preferred sealant in various embodiments of the present invention is a non-organic polymer, one of the preferred non-organic polymers being silicone, which when combined with a blowing agent forms a silicone foam rubber. In some embodiments, it most preferably forms a closed cell silicone foam rubber. The process of forming silicone foam rubber (closed cell) is well known to those skilled in the art. For example, azodicarbonamide blowing agents for producing closed cell foams of many types of polymers and elastomers will be readily recognized by those skilled in the art. Alternatively, perfluoroelastomers ("PFE") or variations of PFE can be used in place of non-organic polymers such as silicone, as they exhibit excellent self-sealing properties when pierced or cut. As yet another alternative, the non-organic polymer can be layered in combination with PFE or variations thereof. In one alternative embodiment, the exemplary silicone can be layered over an underlying fibrous layer, with a layer or region of PFE or variations thereof overlapping at least a portion of the underlying silicone. As yet another alternative, the underlying layer disposed over the fibrous layer can be a PFE, over which a layer of the exemplary silicone can be coated.

[0121] Some embodiments that provide improved self-sealing through puncture as discussed herein, for example suture hole puncture, can be achieved using organic or inorganic polymers or copolymers.

[0122] Generally, the improved self-sealing properties are provided by the properties of the sealing layer, which may comprise, in whole or in part, an organic or inorganic polymer or copolymer, which, when combined with the foaming agents described above, results in an open or closed cell structure formed from the organic or inorganic polymer, or copolymer foam rubber.

[0123] The sealing layer may include a tissue-facing surface layer having either or both an open-cell structure or a closed-cell structure. The sealing layer 18 may include an inorganic or organic polymer or copolymer sealant at the interface. In this embodiment, the sealant covering and / or adhering to the interface is a polymer or copolymer, which may be organic or inorganic, but is not mixed with a foaming agent. Closed and / or open cell foam rubber formed from an organic or inorganic polymer or copolymer may be placed or laminated onto the sealant to form the sealing layer 18.

[0124] Any combination of closed and / or open cell structures can be used in combination with inorganic or organic polymeric or copolymer sealants.

[0125] In some embodiments, the tissue facing surface 20 (tubular), 33 (non-tubular) may comprise either or both of open and closed cell organic or inorganic polymers and / or copolymer foam rubbers.

[0126] In some embodiments, the preferred polymer or copolymer is inorganic, and in some embodiments, the preferred inorganic polymer comprises silicone. When used in combination with a polymer or copolymer foam rubber as described herein, self-sealing of the graft puncture, e.g., suture hole, occurs within one or more of 10 minutes, 5 minutes, 2 minutes, 1 minute, 30 seconds, and / or 10 seconds.

[0127] The sealing layer configurations described above provide improved closure of punctures through the sealing layer and / or fabric layer, improving the return of implanted grafts to hemostasis. For example, but not limited to, a self-sealing layer including a polymeric or copolymeric foam rubber may allow the graft to return to hemostasis following puncture, e.g., allowing the suture hole to self-seal in one or more of 10 minutes or less, 5 minutes or less, 2 minutes or less, 1 minute or less, 30 seconds or less, and / or 10 seconds or less.

[0128] Similarly, a sealing layer configuration having an inorganic sealant layer or region within sealing layer 18, for example, where the sealing layer further comprises a layer of closed cell foam rubber as described herein, may enable restoration of hemostasis following graft puncture, for example, self-sealing of suture holes within one or more of within 10 minutes, within 5 minutes, within 2 minutes, within 1 minute, within 30 seconds, and / or within 10 seconds.

[0129] A sealant layer configuration having a sealant layer of an organic or inorganic polymer or copolymer covering and / or adhering to the interface of a fabric layer, where the sealant layer is covered by or integrated with a closed cell foam rubber as described herein, may enable restoration of hemostasis following graft puncture, e.g., self-sealing of suture holes in one or more of within 10 minutes, within 5 minutes, within 2 minutes, within 1 minute, within 30 seconds, and / or within 10 seconds.

[0130] A sealing configuration having a layer of closed cell foam rubber as described herein, covering and adhering to the interface, the layer of closed cell foam rubber being coated with a sealant layer of an organic or inorganic polymer or copolymer that coats and / or adheres to the interface of a fabric layer, the sealant layer being coated and integrated to allow restoration of hemostasis after graft puncture, for example, self-sealing of suture holes in one or more of within 10 minutes, within 5 minutes, within 2 minutes, within 1 minute, within 30 seconds, and / or within 10 seconds.

[0131] In some embodiments, a hydrogel may be provided along a portion of the implant, the hydrogel being configured to expand upon exposure to water and / or blood to arrest any bleeding that may occur. Thus, the hydrogel may be embedded in the implant at locations that are understood to be prone to bleeding. The hydrogel may be embedded between the fabric and the outer sealing layer, within the fabric, along the outer surface of the sealing layer, or anywhere between the fabric and the sealing layer, in some embodiments.

[0132] In some embodiments, a sleeve may be provided where the anastomosis will be made. In other embodiments, the number of suture holes may be minimized, for example, one suture hole per mm, or 2-3 suture holes per mm. Infection prevention or reduction

[0133] Certain embodiments of implants or prostheses, such as, but not limited to, the tubular or non-tubular grafts, patches, sheets and / or tapes described herein, may be configured to prevent and / or mitigate infection. Techniques for preventing or mitigating adhesion of bacteria or other materials to the tissue surface of graft embodiments are described above and may be useful in preventing or mitigating the formation of infection at the tissue surface.

[0134] Additional infection prevention and mitigation structures are also described below with reference to the figures.

[0135] In general, the various implant or prosthesis embodiments described herein may be provided with an infection prevention or mitigation mechanism and may include (1) an applied infection prevention or mitigation mechanism and / or (2) an embedded or impregnated infection prevention or mitigation mechanism.

[0136] The infection prevention or mitigation mechanism may include one or more, or at least one, antibiotic or antibiotic compound. If present, the at least one antibiotic compound may be applied to the exterior or tissue-facing surface of the subject tubular or non-tubular implant immediately prior to implantation. Application of the at least one antibiotic compound may include spraying, brushing, dipping, or other equivalent application and / or coating methods to provide a coating of at least one antibiotic on the tissue-facing surface, and may also be applied via the scrim 50 or fabric sleeve 52 described above.

[0137] At least one antibiotic or antibiotic compound may be combined with one or more materials to form a composition that is applied to the tissue side surface as described above. Such compositions may include a carrier or other material that provides enhanced adhesion or cohesion to the tissue side surface, thereby ensuring that at least a partial layer of the antibiotic-containing composition is present on the tissue side surface, even on superhydrophobic or water-repellent tissue side surfaces in some embodiments. Additionally, at least one antibiotic may be provided in a microencapsulated form that allows the capsule to adhere to the sealing layer of the tissue side surface. Alternatively, the microencapsulated antibiotic may be held in place by being at least partially embedded and / or pressed into the sealing layer of the tissue side surface. The microencapsulation is preferably biodegradable and / or water-soluble to allow degradation of the capsule to release the encapsulated antibiotic. The degradation of the encapsulated antibiotic may be controlled in a time-controlled release manner by providing a range of capsule thicknesses, biodegradability, water solubility, and / or materials such that some capsules degrade faster and others take longer to degrade.

[0138] As a further alternative, the at least one antibiotic may be in a granular, powdered, or other non-liquid form configured to be at least partially adhered to the sealing layer on the tissue-facing surface or partially embedded or pressed into the sealing layer.

[0139] Other infection prevention and / or mitigation mechanisms may include impregnating the sealing layer with at least one antibiotic compound or composition and / or embedding at least one antibiotic compound or composition within the sealing layer.

[0140] In some cases, the sealing layer may include at least a partial layer of open cell foam rubber as described herein, for example at the interface. In that case, at least one antibiotic compound or composition thereof is disposed in at least a portion of the open cells along or near the interface. The antibiotic compound or composition thereof disposed in the open cells may be liquid, non-liquid, encapsulated or non-encapsulated, and may be time-released as described herein.

[0141] In some embodiments, the infection prevention and / or mitigation mechanism is configured to provide an antibiotic material to prevent or mitigate any infection between the tissue interface and the host tissue. Antibiotics

[0142] As mentioned above, various embodiments of the present invention may further include an effective amount of at least one antibiotic or antibiotic compound coated, embedded and / or incorporated along, along, or within the outer sealing layer or other areas or portions of the tubular or non-tubular graft. The at least one antibiotic may be encapsulated and / or non-encapsulated, or a combination of encapsulated and non-encapsulated, and may be applied to or within the scrim 50 or fabric sleeve 52 described above.

[0143] The degradability or solubility of the capsule encasing the antibiotic may be altered to create a time-controlled release of the encapsulated antibiotic, with some capsules dissolving or degrading faster than others. Additionally, some antibiotics may not be encapsulated and therefore not fully available at the time of implantation. Additionally, the antibiotic may be provided with a biodegradable or water-soluble film layer, providing an additional mechanism for varying the release of the antibiotic over time, whether or not the antibiotic is encapsulated.

[0144] Exemplary antibiotics for use in embodiments of the present invention may include mupirocin, defensin, gentamicin, geneticin, cefminoxime, penicillin, streptomycin, xylitol, lampafin, or other antibiotics. therapeutic cells

[0145] "Therapeutic cells" are defined herein to include at least one cell or type of cell, such as, but not limited to, neural stem cells, that are applied to, embedded within, or incorporated into the tubular or non-tubular grafts herein.

[0146] The therapeutic cells may be obtained from any source and may be at various stages of development and differentiation, so long as the therapeutic cells are sufficient to activate tissue growth into the designated portion of the implant. The therapeutic cells may activate growth along the surface of a fabric or fabric, such as the scrim 50 or fabric sleeve 52 as described above, or along portions of the outer surface of the sealing layer. Additionally, it is recognized that the therapeutic cells may be xenogeneic or allogeneic to the host. Xenogeneic means that the therapeutic cells are obtained from a mammal other than the patient. On the other hand, allogeneic therapeutic cells are obtained from the patient, manipulated outside the body, and then returned to the patient by implanting the implant of the present invention.

[0147] As used herein, "modulatory agent" refers to any molecule that has a growth, proliferation, differentiation, or trophic effect on the transplanted therapeutic cells of the present invention. Any modulating agent capable of modulating the development of transplanted donor cells can be administered by the methods of the present invention. See, for example, Mackay-Sim et al. (2000) Prog. Neurobiol. 62:527-559, which is incorporated herein by reference. Further discussion of modulating agents is provided below, and each such aspect is included in the definition of "modulating agent."

[0148] As used herein, the terms "differentiation" and "maturation" refer to the progression of a cell from a stage with the potential to differentiate into at least two different cell lineages to becoming a specialized cell. Such terms can be used interchangeably for the purposes of the present invention. The term "lineage" refers to all stages of a cell type during development, from the earliest progenitor cell to a fully mature cell (i.e., a specialized cell). Thus, the transplanted therapeutic cells of the present invention can be derived from a pluripotent cell lineage, preferably a neural lineage, and can be at any stage of differentiation. Thus, the present invention also includes therapeutic cells that are naturally programmed to differentiate into only one type of lineage. These types of cells include several types of fibroblasts, or simply differentiated astroglia, neurons, oligodendrocytes, microglia, endothelial cells, etc., and can be derived or isolated from donor tissue or amniotic tissue.

[0149] As used herein, the term "pluripotent stem cells" refers to cells that can differentiate into various lineages. Pluripotent therapeutic cells, e.g., stem cells, are characterized by the ability to undergo continuous cell proliferation, regenerate exact copies of themselves (self-renewal), generate large numbers of local cell progeny, and generate new cells in response to injury or disease. A "pluripotent cell population" refers to a composition of cells that can differentiate into at least two, but less than all, cell lineages. Recent studies have shown that pluripotent stem cells from regions outside the nervous system can generate region-specific neurons when exposed to appropriate environmental cues, without being restricted to their lineage of developmental origin (Lamga et al. (2001) J.Neurosci.20:8727-8735).

[0150] The therapeutic cells of the present invention can be derived from any fetal, amniotic, or adult mammalian tissue, including bone marrow, neural tissue, etc. Additionally, therapeutic cells include, but are not limited to, pluripotent stem cells, progenitor cells, genetically modified cells, T cells, and / or autologous cells.

[0151] Methods for the isolation and transplantation of various progenitor cells derived from different developmental stages in different tissues are well known in the art and have been described, for example, in the striatal cortex (Winkler et al. (1998) Mol. Cell. Neurosci. 11:99-116; Hammang et al. (1997) Exp. Neural. 147:84-95), cortex (Brustle et al. (1998) Nat. Biotechnol 16:1040-1044 and Sabate et al. (1995) Nat. Genet 9:256-260), human telencephalon (Flax et al. (1998) Nature 392:18-24 and Vescovi et al. (1999) Neuron 11:951-966), hippocampus (Gage et al. (1995) J. Neurobiol. 36:249-266 and Suho (1996) Nature 383:624-627), the basal forebrain (Minger et al. (1996) Exp. Neurol. 141:12-24), the ventral midbrain (Winkler et al. (1998) Mol. Cell. Neurosci. 11:99-116, Svendsen et al. (1996) Exp. Neural 137:376-388, Hammang et al. (1998) (1997) Exp. Neurol. 147:84-95, Studer et al. (1997) Nat. Neurosci. 1:290-295, Milward et al. (1997) J. Neurosci. Res. 50:862-871), and the subventricular zone (Milward et al. (1997) Milward et al. (1997) J. Neurosci. Res. 50:862-871), each of which is incorporated herein by reference.

[0152] Additionally, methods for isolating stem cell progeny and promoting their differentiation are also described in US Pat. No. 6,071,889 and US Pat. No. 6,103,530, both of which are incorporated herein by reference.

[0153] The therapeutic cells of the present invention may be modified to enhance tissue growth stimulation. For example, a preferred cell type is human foreskin fibroblasts, which are readily available and can be cultured (see, e.g., U.S. Pat. No. 6,060,048). Such cells are preferably genetically modified using methods well known in the art to express growth factors, neurotransmitters, neuropeptides, or enzymes involved in metabolism or tissue generation. See, e.g., Gage et al. (1987) Neurosci. 23:795-807; Rosenberg et al. (1988) Science 242:1575-1578; Shimohama et al. (1989) Mol. Brain Res. 5:271-278, which are incorporated herein by reference. Alternatively, therapeutic cells of non-neuronal origin, such as epidermal cells, may be converted or induced to differentiate into different types of therapeutic cells. See, e.g., U.S. Pat. No. 6,087,168.

[0154] As discussed, the therapeutic cells of the present invention may be genetically modified prior to implantation of the graft structure into the host tissue. As used herein, the term "genetically modified" refers to cells into which foreign nucleic acid, e.g., DNA, has been introduced. Foreign nucleic acid may be introduced by a variety of techniques, including, but not limited to, calcium phosphate-mediated transfection, DEAE-mediated transfection, microinjection, viral transformation, protoplast fusion, and lipofection. Genetically modified cells may express foreign nucleic acid either transiently or long-term. Generally, if the foreign DNA is not stably integrated into the chromosomal DNA of the transduced cell, transient expression occurs. In contrast, if the foreign DNA is stably integrated into the chromosomal DNA of the transduced cell, long-term expression of the foreign DNA occurs.

[0155] Such genes of interest include neurotransmitter synthesis enzymes (i.e., tyrosine hydrolase (TH) and choline acetyltransferase). Such methods are well known in the art. For example, therapeutic donor cells from various regions of the brain and different stages of development have been isolated and immortalized by genetic modification. For example, olfactory and cerebellar cells have been immortalized using viral myc (v-myc) oncogene to generate cell lines with neuronal and glial phenotypes (Ryder et al. (1990) J. Neurobiol. 21:356). In a similar study by Snyder et al. ((1992) Cell 68:33), a multipotent neuronal cell line was obtained and transplanted into rat cerebellum to form neuronal and glial cells. In another study, mouse neuroepithelial cells were immortalized using a c-myc-containing retroviral vector and cultured with growth factors to form differentiated cells resembling astrocytes and neurons (Barlett et al. (1988) Proc. Natl. Acad. Sci. USA 85:3255). Immunosuppressants

[0156] Alternative embodiments of the present invention may further include an effective amount of at least one immunosuppressant to enhance the survival of the graft, with or without therapeutic cells, through protection from inflammatory responses and / or activation of host immunocompetent cells, either applied along the graft, embedded or incorporated within the graft, or applied to or incorporated into the sleeved scrim 50 or fabrics, fibers and / or yarns and / or non-sealing materials described above.

[0157] When the host tissue immunocompetent cells detect the implanted graft of the present invention, an inflammatory response and / or activation of the host immunocompetent cells may occur. This sequence of events may also reduce the viability of therapeutic cells present along or within the graft. Thus, coating and / or embedding or incorporating immunosuppressants into the graft can play an important role not only in the viability and viability of the graft itself, but also in the viability and viability of therapeutic cells coated or incorporated into the graft. Well-known conventional immunosuppressants that may be used alone or in combination in the present invention include cyclosporine A, tacrolimus, prednisolone, azathioprine, methylprednisolone, mycophenolate mofetil, and sirolimus. Another immunosuppressant includes the application of genetically modified cells expressing Fas ligand. Regulators

[0158] Certain regulators that specifically regulate the growth and differentiation of delivered therapeutic cells when present along or within the implanted exemplary prosthesis or implant, e.g., grafts, patches, sheets and / or tapes, are within the scope of the present invention, including, for example, effective amounts of regulators that promote donor cell survival by regulating immune and inflammatory responses. Such regulators include, for example, cyclosporine and various immunomodulators including interleukins (i.e., IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10), tumor necrosis factors (i.e., TNF-α and TNF-β), interferons (i.e., IFN-α, IFN-β, IFN-γ, IFN-ω, and IFN-τ), and biologically active variants thereof. Further details regarding the administration of these immunomodulatory agents according to the methods of the present application are set forth in U.S. patent application Ser. No. 09 / 733,168, filed Dec. 9, 2000, entitled "Methods for Administering a Cytokine to the Central Nervous System and the Lymphatic System," which is incorporated herein by reference.

[0159] Additional regulators for use in the methods of the invention include CAP23, a major cortical cytoskeleton-associated and calmodulin-binding protein, and GAP43, a nerve growth-associated protein. See, e.g., Frey et al. (2000) J. Cell. Biol. 7:1443-1453. Other factors of interest include bone morphogenetic protein-1 (OP-1), a morphogenetic protein that activates growth, differentiation, and differentiation maintenance (U.S. Pat. No. 6,153,583), sonic hedgehog, a polypeptide that has been shown to promote survival of dopaminergic neurons (Miao et al. (1996) Cell Transplant 55:2-17), and various other glial growth factors (U.S. Pat. Nos. 5,716,930, 6,147,190, 5,530,109), and biologically active variants thereof. All of these references are incorporated herein by reference.

[0160] Other regulators of interest and within the scope of the present invention include growth factors. As used herein, "growth factor" refers to a polypeptide capable of regulating the development of therapeutic cells on or within an implanted graft. Growth factors useful in the methods of the present invention include members of the neurotrophin family (i.e., nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), neurotrophin-4 (also known as NT-4, NT-4 / 5 or NT-5)), fibroblast growth factors (FGF, i.e., basic fibroblast growth factor), epidermal growth factor family (i.e., EGF, TGF.alpha., amphiregulin, heparin-binding EGF-like growth factor (HB-EGF), batacereulin (BTC), neuregulin group), platelet-derived growth factor, insulin, insulin-like growth factors (i.e., IGF-I and IGF-2), ciliary neurotrophic factor (CNTF, glial cell line-derived neurotrophic factor family (GDNF) (i.e., , GDNF and neuturin (NTN), persephin (PSP), and artemin (ART), transforming growth factor beta superfamily (i.e., subfamily includes TGFβ1, TGFβ2, TGFβ3, TGFβ4, TGFβ5, activin, inhibin, decapentrazine), growth differentiation factors (GDFs) (i.e., GDF1, GDF2, GDF3, GDF5, GDF6, GDF7, GDF8, GDF9, GDF9B, GDF10, GDF11, and GDF15), glial cell-derived nexins, activity-dependent neurotrophic factor (ADNF), glial cell growth factor (GGF). Additionally, it is recognized that biologically active variants of these growth factors are also useful in the methods of the present invention.

[0161] The modulators of the present invention may be derived from any animal species, including, but not limited to, rodents, birds, canines, bovines, porcines, equines, and preferably humans. Preferably, the modulator administered is derived from the same species as the animal receiving treatment.

[0162] Biologically active variants of the regulatory polypeptide (i.e., growth factors such as IGF-I, NGF, basic FGF, cytokines, etc.) are also encompassed in the various methods and pharmaceutical compositions of the present invention. Such variants should retain the biological activity of the regulator, in particular the ability to regulate donor cell development (i.e., the ability to promote survival, maintain a desired phenotype, and / or regulate the developmental cues produced by donor cells). For example, if the regulatory polypeptide is a growth factor such as IGF-I, NGF-I, or a member of the FGF family, the ability to bind to the respective receptor site is retained. Such receptor binding activity can be measured using standard biological assays.

[0163] One such regulator growth factor is useful in the present invention is IGF-I. The term "IGF-I" as used herein refers to insulin-like growth factor I (IGF-I), a single-chain peptide with 70 amino acids and a molecular weight of about 7,600 daltons. Insulin-like growth factor I activates mitosis and growth processes associated with cell development. The amino acid and nucleotide sequences of IGF-I are well known in the art. See, for example, U.S. Patent No. 5,324,639, which discloses the human IGF-I sequence, Genbank Accession No. X15726, which discloses the bovine IGF-I sequence, and Genbank Accession No. X06043, which discloses the rat IGF-I sequence. Each of these references is incorporated herein by reference.

[0164] In another embodiment of the present invention, the regulator can comprise a member of the FGF growth factor family and / or a biologically active variant thereof. The fibroblast growth factor family includes a group of structurally related proteins that bind to heparin with high affinity. FGF family members have mitogenic activity and induce proliferation of a wide variety of cells. FGF family members are also involved in angiogenesis, differentiation, cell migration, embryonic development, and neuronal maintenance / survival. The term "FGF" as used herein refers to a member of the fibroblast growth factor family, including, for example, FGF-1 (acidic FGF), FGF-2 (basic FGF), FGF-3, FGF-4, FGF-5, FGF-6, FGF-8, FGF-9, FGF-98, or biologically active fragments or variants thereof. The amino acid sequences and methods of production of many members of the FGF family are well known in the art.

[0165] In another embodiment of the invention, the modulating agent may comprise nerve growth factor (NGF) or a biologically active variant thereof. NGF was originally isolated as a complex with a molecular weight of 130 kDa and a sedimentation coefficient of 7S. The 7S complex contains three subunits, with the ".beta." subunit being responsible for all of the biological activities of NGF. Nerve growth factor specifically activates cell division and growth processes in nerve cells and regulates development (i.e., affects repair, survival, and differentiation). Preferred amino acid sequences of human precursor pro-NGF and human mature NGF are described in U.S. Pat. No. 5,288,622, which is incorporated herein by reference.

[0166] The NGF used in the present invention may be in a substantially purified native form, or in a recombinantly produced form, or in a chemically synthesized form. For example, NGF can be directly isolated from cells that naturally express NGF. NGF can also be recombinantly produced in eukaryotic or prokaryotic expression systems, as described in Edwards et al. (1988) Mol. Cell. Biol. 8:2456, U.S. Patent No. 5,986,070, and U.S. Patent No. 6,005,081, all of which are incorporated herein by reference. Alternatively, the regulator of the present invention may include erythropoietin (EPO), brain-derived neurotrophic factor (BDNF), and epidermal growth factor (EGF). Each of the regulators described herein plays an important role in the in vivo survival and differentiation of cells for treatment of the methods and pharmaceutical compositions of the present invention.

[0167] Administration of an effective amount of at least one regulating agent according to the methods of the present invention, including but not limited to coating along or incorporating into or embedding into a sealing layer or other area of ​​an implanted prosthesis or implant such as a graft, patch, sheet and / or tape, and further incorporating into a scrim 50, or a sleeve 52 of fabric, fiber or yarn or other non-sealing material, in combination with the therapeutic cells, regulates the development of therapeutic cells in the implant. The term "modulating development" as used herein means, inter alia, that the modulating agent promotes survival, differentiation, axonal development, dendritic development, and / or proliferation of transplanted therapeutic cells, improves adhesion of transplanted therapeutic cells to surrounding tissue (i.e., incorporation into parenchymal tissue), improves the ability of transplanted therapeutic cells to establish synaptic connections with host neurons (i.e., promotes neurofibrosis in donor cells, increases neurofiber projection distance of donor cells, or promotes a neurofiber fate of donor cells), and / or directs transplanted therapeutic cells to follow a particular neural lineage (i.e., adopt a neuronal (e.g., GABAergic, dopaminergic, cholinergic, hippocampal neuron), astrocyte, or oligodendrocyte cell fate). Additionally, it is recognized that the modulating agent can enhance survival of transplanted donor cells by modulating the immune response of the subject. By "modulation" is intended down-regulation of immune or inflammatory responses (ie, affecting systemic immune function, antigen presentation, cytokine production, lymphocyte proliferation, and invasion of lymphocytes and macrophages).

[0168] Furthermore, administration of modulating agents is known to "modulate the development" of transplanted therapeutic donor cells by influencing the developmental cues released by the transplanted cells (i.e., encouraging the donor cells to release neurotransmitters such as dopamine, acetylcholine, GABA, or other neuroprotective factors). Thus, the non-invasive methods of the present invention can improve the function and repair of the surrounding host tissue (i.e., improving nerve fiber formation, nerve fiber projection distance, and / or enhancing nerve fiber density). Pharmaceutical Compositions

[0169] The pharmaceutical compositions can be applied to or incorporated into tubular or non-tubular prostheses or implants, such as grafts, patches, sheets or tapes. They may contain one or more of antibiotics, therapeutic cells, regulators and / or immunosuppressants. Such pharmaceutical compositions may contain, in addition to an effective amount of at least one therapeutic cell, for example, at least one regulator as described above, at least one delivery enhancer as described above, at least one antibiotic, and / or at least one immunosuppressant, all of which are described herein. Furthermore, all of these substances may be applied to or incorporated within the graft, whether as a composition or as individual substances, and / or may be encapsulated as described herein, and / or coated or covered with a degradable or water-soluble film. In either case, time-controlled release of various substances may be achieved by the methods described herein.

[0170] Additionally, pharmaceutical compositions of antibiotics, therapeutic cells, modulators, and / or immunosuppressants, and / or any of the listed substances may include any pharma- ceutically acceptable additives, carriers, and / or adjuvants that facilitate or allow for retention of the substance along with or within the graft, but also allow for easy release of the substance from the graft at the designed time.

[0171] "Pharmaceutically acceptable carrier" refers to a carrier conventionally used in the art to facilitate the storage, administration, and / or biological activity of therapeutic cells, regulators, antibiotics, and / or immunosuppressants in the pharmaceutical composition of the present invention. The carrier may also reduce undesirable side effects of the components of such pharmaceutical compositions. A suitable carrier should be stable, i.e., incapable of reacting with other components in the formulation. It should not cause significant local or systemic side effects in the recipient at the dosages and concentrations used for treatment. Such carriers are generally known in the art.

[0172] Carriers suitable for various embodiments of the invention include those conventionally used for stable polymers such as albumin, gelatin, collagen, polysaccharides, monosaccharides, polyvinylpyrrolidone, polylactic acid, polyglycolic acid, polymeric amino acids, fixed oils, ethyl oleate, liposomes, glucose, sucrose, lactose, mannose, dextrose, dextran, cellulose, mannitol, sorbitol, polyethylene glycol (PEG), etc. Additionally, pharmaceutical compositions can include microparticles that act as adhesive materials for cells and cell aggregates, organic and inorganic compounds, or microparticles with other substances such as antibiotics or immunosuppressants for the graft itself. These compounds include several types of adhesion molecules, gels (which act as encapsulation / embedding materials for cells), components of the extracellular matrix, and organic and / or inorganic particles such as fibrin, fibronectin, carbon or clay and dextran particles, and compositions thereof.

[0173] Water, saline, aqueous dextrose, glycols are preferred liquid carriers, especially for solutions (if isotonic). Carriers can be selected from a variety of oils, including those of petroleum, animal, vegetable or synthetic origin, such as peanut oil, soybean oil, mineral oil, sesame oil, and the like. Suitable pharmaceutical excipients include starch, cellulose, talc, glucose, lactose, sucrose, gelatin, malt, rice, flour, chalk, silica gel, magnesium stearate, sodium stearate, glycerol monostearate, sodium chloride, dried skim milk, glycerol, propylene glycol, water, ethanol, and the like. The compositions can be subjected to conventional pharmaceutical manufacturing procedures, such as sterilization, and can contain conventional pharmaceutical excipients, such as preservatives, stabilizers, wetting agents, emulsifiers, salts for adjusting osmotic pressure, buffers, and the like. When the carrier is liquid, it is preferred that the carrier is hypotonic or isotonic with respect to body fluids, and has a pH in the range of 4.5 to 8.5.

[0174] Other components that are acceptable in pharmaceutical compositions include, but are not limited to, water, saline, and tonicity modifiers, such as buffers, including phosphates, citrates, succinates, acetic acid, and other organic acids or their salts.Usually, pharmaceutically acceptable carriers also include one or more stabilizers, reducing agents, antioxidants, and / or antioxidant chelating agents.The use of buffers, stabilizers, reducing agents, antioxidants, and chelating agents in the preparation of protein-based compositions, particularly pharmaceutical compositions, is well known in the art. Wang et al. (1980) J. Parent. Drug Assn. 34(6), 452-462; Wang et al. (1988) J. Parent. Sci. Tech. 42:S4-S26 (Suppl.); Lachman et al. (1968) Drug and Cosmetic Industry 102(1):36-38, 40, and 146-148; Akers (1988) J. Parent. Sci. Tech. 36(5):222-228; and Methods in Enzymology, Vol. 25, Colowick and Kaplan (eds.), Reduction of Disulfide Bonds in Proteins with Dithiothreitol, Konigsberg, pp. 185-188.

[0175] Additionally, some embodiments of the exemplary prostheses or implants described herein, such as tubular or non-tubular grafts, patches, sheets, tapes, etc., may include a sealing layer that includes silver or colloidal silver, a known antimicrobial agent, embedded in, doped into, and / or coated onto the sealing layer. The sealing layer may include silicone that includes silver or colloidal silver.

[0176] In some embodiments, a layered approach to reducing seroma and / or infection with implanted tubular or non-tubular grafts may be employed, for example, an inner or outer coating of the carrier and an antibiotic surgically attached to the carrier may be provided. Radiopaque and / or visible markings

[0177] Certain embodiments of tubular or non-tubular prostheses and implants, such as grafts, patches, sheets, tapes, etc. described herein include radiopaque markings to aid the physician in locating the graft using imaging devices and techniques to verify its proper location, assess the condition of the implanted graft, and / or prevent occlusion of branch arteries and veins. A non-limiting list of imaging devices and / or techniques includes x-ray, fluoroscopy, CT scan, and MRI.

[0178] Visual markings are provided to aid the practitioner in determining whether a subject graft has a torsion or other abnormality, and may represent the length or other dimension of the graft under physiological pressure. For example, a marking indicating a 1 cm length increment may be measured at 1 cm under physiological pressure and may be measured at lengths greater or less than 1 cm under conditions other than physiological pressure. As defined herein, a visual marking is a marking that is visible to the practitioner's naked eye and is enhanced only with the use of magnifying glasses and without the aid of an imaging device or other enhancement technique.

[0179] 8 and with continued reference to FIGS. 1-7, the radiopaque markings may be comprised of one or more radiopaque regions located at one or more locations along the implant. One or more of the radiopaque regions may be located at the fabric layer interface, i.e., below the sealant layer 18. Other radiopaque regions may be embedded within the sealant layer 18 without structurally connecting with the fabric layer 18 interface.

[0180] FIG. 8 shows exemplary radiopaque markers incorporated into the Valsalva graft as rings at the sinotubular junction and aortic root to be used as "landing zones" for future fluoroscopically guided valvular disease treatments. A first radiopaque marker ring is seen to be located between the collar and the Valsalva skirt, and a second radiopaque marker ring is located at the upper end of the Valsalva skirt. Radiopaque markers may be used with other tubular or non-tubular grafts described herein. For example, but not limited to, radiopaque materials or markers may have complete or partial or intermittent rings around branch locations, such as native vessels or grafts, to allow identification during fluoroscopic interventions. See FIG. 8 for exemplary branch locations of radiopaque markers or rings.

[0181] In some embodiments, the radiopaque regions or markings may be visible to the naked eye of a physician without imaging, equipment or other visual aids, in which embodiment the visible radiopaque regions may also function as visual markings as described above.

[0182] In other embodiments, the radiopaque areas or markings are not visible to the naked eye of a physician and must be visualized using imaging techniques.

[0183] The visual markings described above aid in the rapid assessment of whether a subject graft is twisted or otherwise abnormal and may represent the length or other dimensions of the graft under physiological pressure. For example, a marking indicating 1 cm length increments may be measured at 1 cm under physiological pressure and may be measured at lengths greater or less than 1 cm under conditions other than physiological pressure.

[0184] In an exemplary tubular graft, two or more visual markings may be provided at or near the tissue-facing surface of the sealing layer. In certain embodiments, the two or more visual markings may be aligned with the undeformed longitudinal axis of the tubular graft and may be radially spaced apart from one another. In certain embodiments, the two or more radially spaced visual markings may be visually distinct from one another to aid the practitioner in, among other things, assessing whether the graft is kinked. For example, the markings may be different in color or may provide a visually distinct feature between the markings, such as a continuous line versus a dashed or dotted line, or discrete points versus a dotted or continuous line.

[0185] Various embodiments of tubular or non-tubular grafts described herein can be used as the dissection surface. Generally, graft surfaces having a woven fabric allow for excellent fixation to adjacent tissue. If the woven fabric is completely covered on the opposite side with a non-organic polymer or copolymer, such as silicone, tissue cannot grow onto the surface. See, for example, Figures 1-3C. A preferred material and design is shown in Figures 9 and 10 and consists of an exemplary non-tubular graft 70 with an outer sealing layer 18 that completely covers an embedded polyester mesh woven material 72 that is partially exposed on the opposite side. A portion of the polyester mesh woven material 72 is embedded within or covered by the outer sealing layer 18, which may be comprised of an organic or inorganic polymer or copolymer. A preferred polymer comprises silicone, but other polymers may be used as long as tissue ingrowth through or into the outer sealing layer material is not permitted or possible. As shown in FIG. 9, in some cases, pockets of the exemplary silicone are exposed on the tissue surface, and tissue ingrowth may occur in a pattern corresponding to the exposed polyester mesh fabric. In other embodiments, the exemplary silicone is prevented from reaching the tissue surface, and thus the entire tissue surface is available for tissue ingrowth. However, the opposing surface of the outer sealing layer 18 is not available for tissue ingrowth. This is useful for providing a surgical incision surface for post-implantation surgery. As previously mentioned, such a surgical incision surface can be provided on both tubular and non-tubular implants as described herein.

[0186] The surgical cutting surface embodiments may be used in a variety of ways, including but not limited to the following:

[0187] Wrapping of ventricular assist devices ("VADs"), including right ventricular assist devices and left ventricular assist devices.

[0188] Leaflets of a heart valve.

[0189] The base or commissure of a heart valve.

[0190] Extracorporeal membrane oxygenation (“ECMO”).

[0191] Guided tissue regeneration.

[0192] Venous surgery.

[0193] Rotator cuff buttress.

[0194] Knee joint pads.

[0195] Ligaments of the legs.

[0196] Head pad.

[0197] Dental implants.

[0198] Rhinoplasty.

[0199] burn.

[0200] Reinforcement of heart valves.

[0201] Below, selected invention embodiments are described. 1. A tubular or non-tubular implant or prosthesis configured to facilitate removal from a living body, comprising: a woven layer including a plurality of interstices and / or pores and defining an interface and an opposing surface; a non-porous, non-organic polymeric sealing layer adhered to the interface and defining a tissue-facing surface, the sealing layer being configured to partially penetrate at least a portion of the plurality of gaps and / or pores on an opposing surface of the fabric layer; Equipped with the non-porous, non-organic polymer of the sealing layer does not penetrate to the opposite surface of the fabric layer; the non-porous, non-organic polymer of the sealing layer has a heat resistance greater than a heat resistance of an organic polymer or organic copolymer, such that the outer layer is configured to resist and / or inhibit damage from applied electrosurgical energy; This allows the inner fibrous layer to be protected, resulting in a tubular or non-tubular implant or prosthesis that resists and / or inhibits damage from the applied electrosurgical energy. 2. A tubular or non-tubular implant or prosthesis as described in claim 1, wherein the non-porous, non-organic polymer of the sealing layer has molecular bonds with a bond energy higher than the bond energy of carbon bonds. 3. The tubular or non-tubular implant or prosthesis of claim 1, wherein the sealing layer is hydrophobic. 4. The tubular or non-tubular implant or prosthesis of claim 1, wherein the sealing layer is superhydrophobic and has a sliding angle of less than 10 degrees. 5. A tubular or non-tubular implant or prosthesis as claimed in claim 1, wherein the sealing layer is ultra-hydrophobic, has a sliding angle of less than 10 degrees, and excludes blood. 6. The tubular or non-tubular implant or prosthesis of claim 1, wherein the sealing layer is free of gaps or pores. 7.0 mL / cm 2 13. The tubular or non-tubular implant or prosthesis of claim 1, further having a water permeability of 1.0 to 1.0 mm / min. 8. The tubular or non-tubular implant or prosthesis of claim 1, wherein the tissue side surface of the outer layer has a root mean square surface roughness of 35 nm or less, and the surface roughness of the tissue side surface is configured to prevent adhesion of body tissue or platelets to at least a portion of the tissue side surface after implantation of the tubular implant or prosthesis. 9. The tubular or non-tubular implant or prosthesis of claim 1, wherein the sealing layer is configured to prevent adhesion of biological tissue and / or platelets to at least a portion of the tissue-facing surface. 10. The tubular or non-tubular implant or prosthesis of claim 1, wherein the sealing layer is configured to prevent bacterial adherence to the tissue-facing surface. 11. The tubular or non-tubular implant or prosthesis of claim 1, wherein the sealing layer is configured to prevent the formation of seroma along the tissue side surface. 12. The tubular or non-tubular implant or prosthesis of claim 1, wherein the sealing layer is configured to prevent the formation of infection along the tissue-facing surface. 13. The tubular or non-tubular implant or prosthesis of claim 1, wherein at least a portion of an opposing surface of said fabric layer allows for tissue ingrowth. 14. The tubular or non-tubular implant or prosthesis of claim 1, wherein the sealing layer prevents transmural communication or migration from the luminal surface to the outer layer. 15. The tubular or non-tubular implant or prosthesis of claim 1, wherein at least a portion of said sealing layer is constructed of a color that contrasts with blood and tissue. 16. A zone 1 having a first side bounded by the opposing surface of the fibrous layer, the plurality of interstices and / or pores being free of the non-porous, non-organic polymer of the sealing layer; a zone 2 disposed within the fibrous layer, adjacent a first side and bounded by the zone 1, and on the opposite side by the interface, at least a portion of the plurality of interstices and / or pores comprising the non-porous, non-organic polymer; a zone 3 bounded adjacent the interface on the inside and bounded on the outside by the tissue-facing surface defined by the sealing layer, consisting only of the non-porous, non-organic polymer, and defining a thickness; 2. The tubular or non-tubular implant or prosthesis of claim 1, comprising three cross-sectional zones including: 17. The tubular or non-tubular implant or prosthesis of claim 16, wherein the non-porous, non-organic polymer of Zone 3 prevents ingrowth or transmural communication of biological tissue into Zone 3 through the interface. 18. A tubular or non-tubular implant or prosthesis according to claim 17, wherein ingrowth of living tissue into at least a portion of zone 2 and into zone 1 is not prevented. 19. The tubular or non-tubular implant or prosthesis of claim 1, wherein the non-porous, non-organic polymer includes a foaming agent that forms a polymeric foam rubber. 20. The tubular or non-tubular implant or prosthesis of claim 19, wherein the polymeric foam rubber forms a polymeric foam rubber closed cell structure. 21. A tubular or non-tubular implant or prosthesis as described in claim 19, wherein at least the tissue-facing surface of the sealing layer has one or both of an open cell polymeric foam rubber structure and a closed cell polymeric foam rubber structure. 22. The tubular or non-tubular implant or prosthesis of claim 1, wherein the graft is tubular and configured for connection to one or both of an inlet or outlet of a left ventricular assist device or a right ventricular assist device. 23. The tubular or non-tubular implant or prosthesis of claim 1, wherein the graft is tubular and configured with a Valsalva aortic root graft. 24. The tubular or non-tubular implant or prosthesis of claim 1, wherein the sealing layer provides protection and insulation against heat transfer and / or electrical energy to and / or through the textile layer during endovascular procedures. 25. The tubular or non-tubular implant or prosthesis of claim 24, wherein the sealing layer protects blood cells within or adjacent to the fabric from thermal or electrical damage. 26. The tubular or non-tubular implant or prosthesis of claim 24, wherein the sealing layer protects therapeutic cells, therapeutic drugs and / or antibiotics or other substances attached to or incorporated into the textile fibers from thermal or electrical damage. 27. The tubular or non-tubular implant or prosthesis of claim 24, wherein the sealing layer protects tissue on or near the textile fibers from thermal or electrical damage. 28. A tubular or non-tubular implant or prosthesis configured to control tissue ingrowth and incorporation of the graft into the body and to facilitate removal from the body, comprising: a fibrous layer including a plurality of interstices and / or pores and defining an interface and an opposing surface; a sealing layer adhered to at least a portion of the interface and defining a tissue-facing surface, the non-porous, non-organic polymer configured to partially penetrate at least a portion of the plurality of interstices and / or pores on the opposing surface of the fabric layer; Equipped with A tubular or non-tubular implant or prosthesis, wherein the sealing layer is interrupted by at least one fabric scrim configured to promote tissue ingrowth. 29. The implant or prosthesis of claim 28, wherein the at least one fabric scrim is operatively connected to the fibrous layer at the interface. 30. The implant or prosthesis of claim 28, wherein the at least one fabric scrim is embedded within the sealing layer, and the at least one fabric scrim is spaced from the fibrous layer by the non-porous, non-organic polymer of the sealing layer. 31. The implant or prosthesis of claim 28, wherein at least one of the group consisting of antibiotics, therapeutic cells, regulators, and immunosuppressants is embedded in and / or operatively connected to said at least one scrim. 32. An implant or prosthesis as claimed in claim 31, wherein at least one of the Markush group of claim 28 is encapsulated in a water-soluble, biodegradable or biodissolvable material. 33. The implant or prosthesis of claim 28, further comprising a water soluble, biodegradable, or biodissolvable film covering said at least one scrim. 34. The implant or prosthesis of claim 28, wherein at least a portion of the at least one scrim has a contrasting color to blood and / or tissue. 35. The implant or prosthesis of claim 34, wherein at least a portion of the at least one scrim is blue in color. 36. A tubular or non-tubular implant or prosthesis configured to have radiopacity, a fibrous layer including a plurality of interstices and / or pores and defining an interface and an opposing surface; a non-porous, non-organic polymeric sealing layer adhered to at least a portion of the interface and defining a tissue-facing surface, the non-porous, non-organic polymer configured to partially penetrate at least a portion of the plurality of interstices and / or pores on an opposing surface of the fabric layer; one or more radiopaque regions comprising a radiopaque material, said radiopaque material being embedded within a sealing layer and / or attached to said interface of said fabric layer; A tubular or non-tubular implant or prosthesis comprising: 37. The implant or prosthesis of claim 36, wherein the implant or prosthesis comprises a Valsalva graft and the one or more radiopaque regions comprise radiopaque rings configured to be located at the connection to the aortic root and / or the sinotubular junction. 38. The implant or prosthesis of claim 36, wherein the radiopaque ring is a complete ring or a partial intermittent ring. 39. The implant or prosthesis of claim 36, wherein the one or more radiopaque regions are configured to be visible to the practitioner to allow assessment and diagnosis of the location and condition of the implant. 40. A tubular or non-tubular implant or prosthesis, a fibrous layer including a plurality of interstices and / or pores and defining an interface and an opposing surface; a sealing layer adhered to at least a portion of the interface and defining a tissue-facing surface, the non-porous, non-organic polymer configured to partially penetrate at least a portion of the plurality of interstices and / or pores on the opposing surface of the fabric layer; one or more exposed fiber layers exposed within, not covered by, and at least partially surrounded by the sealing layer; A tubular or non-tubular implant or prosthesis comprising: 41. The implant or prosthesis of claim 40, wherein the one or more exposed fiber layers are configured to allow tissue ingrowth. 42. The implant or prosthesis of claim 41, wherein one or more exposed fiber layers are configured for use as a cutting surface.

[0202] The description of the invention and its applications set forth herein is illustrative and is not intended to limit the scope of the invention. Features of the various embodiments disclosed herein may be combined with other embodiments within the contemplation of the present invention. Variations and modifications of the embodiments disclosed herein are possible, and practical alternatives and equivalents to the various elements of the embodiments will become apparent to those skilled in the art upon study of this patent document. These and other variations and modifications of the embodiments disclosed herein may be made without departing from the scope or spirit of the present invention.

Claims

1. 1. A tubular or non-tubular implant or prosthesis configured to prevent or reduce infection when implanted in a living body, comprising: a fibrous layer including a plurality of interstices and / or pores and defining an interface and an opposing surface; a sealing layer having a polymer and / or copolymer attached to the interface and defining a tissue-facing surface, the polymer and / or copolymer configured to at least partially penetrate at least a portion of a plurality of gaps and / or pores at the interface of the textile layer; at least one infection prevention or mitigation mechanism disposed on the tissue-facing surface or embedded within the sealing layer; A tubular or non-tubular implant or prosthesis comprising:

2. the at least one infection prevention or mitigation mechanism comprises at least one antibiotic compound disposed on the tissue-facing surface of the sealing layer; 2. A tubular or non-tubular implant or prosthesis according to claim 1.

3. At least a portion of the sealing layer is configured to absorb the at least one antibiotic compound.

3. A tubular or non-tubular implant or prosthesis according to claim 2.

4. the at least one infection prevention or mitigation mechanism comprises at least one antibiotic compound embedded within the sealing layer; 2. A tubular or non-tubular implant or prosthesis according to claim 1.

5. the at least one antibiotic compound is embedded in or on the tissue-facing surface; 5. A tubular or non-tubular implant or prosthesis according to claim 4.

6. The at least one antibiotic compound is encapsulated in a water-soluble, biodegradable, or bioabsorbable capsule.

6. A tubular or non-tubular implant or prosthesis according to claim 5.

7. at least a portion of the tissue-facing surface of the sealing layer has an open cell foam rubber structure formed from the polymer and / or the copolymer in combination with a foaming agent; the at least one antibiotic compound is disposed within at least one open cell of the open cell foam rubber structure; A tubular or non-tubular implant or prosthesis according to any one of claims 1 to 6.

8. The sealing layer comprises one or more of an impermeable, non-porous, non-organic polymer, a non-organic open cell foam rubber structure, and a non-organic closed cell foam rubber structure. A tubular or non-tubular implant or prosthesis according to any one of claims 1 to 7.

9. The sealing layer comprises one or more of an organic polymer, a non-organic or organic open cell foam rubber structure, and a non-organic or organic closed cell foam rubber structure. A tubular or non-tubular implant or prosthesis according to any one of claims 1 to 7.

10. the organic or non-organic open cell foam rubber structure having at least a portion of the tissue-facing surface; the impermeable, non-porous, non-organic polymer is adhered to the interface of the fibrous layer; 10. A tubular or non-tubular implant or prosthesis according to claim 9.

11. The at least one antibiotic compound is configured for time-controlled release from the sealing layer and / or the tissue-facing surface and / or the encapsulation. A tubular or non-tubular implant or prosthesis according to any one of claims 1 to 10.

12. The at least one antibiotic compound is selected from the group consisting of mupirocin, defensin, gentamicin, geneticin, cefminoxime, penicillin, streptomycin, xylitol, and lampafin; 12. A tubular or non-tubular implant or prosthesis according to any one of claims 1 to 11.

13. A tubular or non-tubular implant or prosthesis having improved self-sealing capabilities, comprising: a fibrous layer having a plurality of interstices and / or pores and defining an interface and an opposing surface; a self-sealing layer having a polymer or copolymer foam rubber adhered to at least the interface of the fibrous layer, defining a tissue-facing surface, adhered to at least a portion of the opposing surface of the fibrous layer, and configured to at least partially penetrate at least a portion of the plurality of gaps and / or pores of the fibrous layer; Equipped with The sealing layer has a time to achieve hemostasis after a suture needle is pierced through the tubular or non-tubular implant or prosthesis within one or more of the following time ranges: 10 minutes or less, 5 minutes or less, 2 minutes or less, 1 minute or less, 30 seconds or less, and 10 seconds or less. Tubular or non-tubular implants or prostheses.

14. At least a portion of the self-sealing layer comprises a polymer or copolymer foam rubber having a closed cell structure; 14. A tubular or non-tubular implant or prosthesis according to claim 13.

15. At least the tissue-facing surface of the sealing layer has one or both of an open cell polymeric foam rubber structure and a closed cell polymeric foam rubber structure.

14. A tubular or non-tubular implant according to claim 13.

16. The polymer or copolymer of the polymer or copolymer foam rubber is a non-organic polymer; 14. A tubular or non-tubular implant according to claim 13.

17. The polymer or copolymer foam rubber has a silicone foam rubber selected from either one or both of a closed cell structure and an open cell structure.

14. A tubular or non-tubular implant according to claim 13.

18. A tubular or non-tubular implant or prosthesis having improved visibility and / or radiopacity markings, comprising: a fibrous layer having a plurality of interstices and / or pores and defining an interface and an opposing surface; a self-sealing layer having a polymer or copolymer foam rubber adhered to at least the interface of the fibrous layer, defining a tissue-facing surface, adhered to at least a portion of the opposing surface of the fibrous layer, and configured to at least partially penetrate at least a portion of the plurality of interstices and / or pores of the fibrous layer; one or more radiopaque regions disposed at one or more locations along and / or around the tubular or non-tubular implant or prosthesis, located at the interface of the fabric layer, and / or embedded within the sealing layer; A tubular or non-tubular implant or prosthesis comprising:

19. The one or more regions of radiopaque are configured to be visible to a physician without the aid of an imaging device.

19. A tubular or non-tubular implant or prosthesis according to claim 18.

20. the one or more regions of radiopacity are configured to be invisible to a physician without the aid of an imaging device; 20. A tubular or non-tubular implant or prosthesis according to claim 18 and / or 19.

21. the implant is tubular and further comprises at least two markings disposed on or near the tissue surface of the sealing layer along a longitudinal axis of the implant, the at least two markings being radially spaced apart from one another around the circumference of the tubular implant or prosthesis; 21. A tubular or non-tubular implant or prosthesis according to any one of claims 18 to 20.

22. At least one of the at least two markings has a continuous linear marking.

22. A tubular or non-tubular implant or prosthesis according to claim 21.

23. At least one of the at least two markings has a dashed or dotted linear marking.

22. A tubular or non-tubular implant or prosthesis according to claim 21.

24. The at least two markings are configured to be visible to the naked eye of a physician.

24. A tubular or non-tubular implant or prosthesis according to any one of claims 18 to 23.

25. A tubular or non-tubular implant or prosthesis configured to withstand or resist damage from application of electrocautery energy, comprising: a fibrous layer having a plurality of interstices and / or pores and defining an interface and an opposing surface; a sealing layer adhered to the interface and defining a tissue-facing surface, the sealing layer being a non-porous, non-organic polymer configured to partially penetrate at least a portion of the plurality of gaps and / or pores on an opposite surface of the fabric layer; Equipped with the non-porous, non-organic polymer of the sealing layer does not penetrate to the opposite surface of the woven fibrous layer; the outer layer is configured to resist and / or inhibit damage from applied electrosurgical energy; thereby resisting and / or inhibiting damage to the inner fibrous layer resulting from the applied electrosurgical energy. Tubular or non-tubular implants or prostheses.

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