RU2805364C2 - Biodegradable mesh implant for soft tissue restoration, in particular hernioplasty - Google Patents

Abstract

FIELD: surgery.

SUBSTANCE: group of inventions can be used for the restoration of soft tissues in surgical hernioplasty, for the healing of chronic wounds or for the surgical healing of fistulas in the patient’s body. The group includes a biodegradable mesh implant, a method of producing a mesh implant, and a kit. A biodegradable mesh implant contains a porous, hydrophilic, biodegradable polymer support mesh and fibroblasts on or within the polymer support mesh. The supporting mesh contains a spongy structure with interconnected pores of different sizes, and has a contact angle of less than 75° and is made of at least a polymer that includes polylactic acid as a main component. The kit contains a biodegradable mesh implant and an additional polymer support mesh.

EFFECT: obtaining biodegradable mesh implant for soft tissue restoration, in particular hernioplasty.

18 cl, 6 dwg

Description

[001] The present invention relates to a biodegradable mesh implant containing a polymeric support mesh seeded with fibroblasts for use in soft tissue repair in general and, in particular, in surgical hernia repair, as claimed in claim 1 of the claims. The present invention also relates to a method for producing a mesh implant and to a kit containing a mesh implant according to the present invention and an additional polymeric support mesh.

[002] Wound healing is a complex process that involves the orchestration of a number of interconnected cellular events and cytokine cascades. The major phases of wound healing include fibrin clot formation followed by infiltration of inflammatory cells and fibroblasts, granulation tissue formation and angiogenesis, and reepithelialization. Growth factors and cytokines play an important role, which are first supplied by degranulating platelets and then by fibroblasts and inflammatory cells, in particular neutrophils and macrophages. Due to its complex nature, the wound healing process is also fragile and susceptible to interruption or pathology, resulting in the formation of chronic wounds that are severely hampered in healing. Therefore, depending on the size and type of soft tissue defect, surgical repair may be required to promote the wound healing process and reduce the risk of complications.

[003] In the field of surgical reconstruction of soft tissues, a mesh implant consisting of an absorbable or non-absorbable material is often used, which is inserted to cover the area of the tissue defect. The mesh implant is used as a mechanical closure of the defect and to provide a supporting structure for regenerating tissue, i.e. for growing cells that form strong fibrous scar tissue around the mesh implant.

[004] In addition to chronic wounds, mesh implants are often used surgically to repair hernia defects, particularly in the abdominal wall, which may be the result of trauma, tumor resection, or prolapse. In general terms, a hernia can be described as the passage of organs or parts of organs from a natural body cavity through a preformed or acquired gap. The most common types of hernia are inguinal or femoral hernia, hiatal hernia, umbilical hernia and incisional hernia, the latter being a hernia that has pushed through a past surgical incision or operation. In surgical hernia repair, a mesh implant is inserted to cover the area of the defect in the abdominal wall to achieve tension-free closure - with or without suturing the surrounding muscles and fascia. This can be done under local or general anesthesia using an open incision technique or a laparoscope in a minimally invasive procedure.

[005] The reasons why hernias occur are not yet fully understood. One proposed theory in this area is that some patients, due to disorders of collagen metabolism, have a genetic predisposition to develop recurrent hernias, especially in older patients. The altered ratio of collagen types I and III in these patients, with an increase in collagen type III, is thought to reduce the mechanical strength of connective tissues. It is likely that decreased tensile strength of type III collagen plays a key role in the development of incisional hernias, see KLINGE, U. et al. Abnormal collagen I to III distribution in the skin of patients with incisional hernia. Eur Surg Res. 2000, vol. 32, no. l, pp. 43-48. Impaired collagen production is also thought to be a contributing factor to the development of chronic wounds, i.e. wounds that do not heal properly and open again and again, especially in patients with diabetes and patients with vascular disorders.

[006] Commercially available meshes used today in surgical repair of soft tissues are either non-degradable or completely degradable and are absorbed into the patient's body after a specific time.

[007] Non-absorbable mesh implants are most often made from a variety of plastics that are known to remain biostable and safe for several years after implantation. However, the introduction of foreign material into the human or animal body may be accompanied by side effects such as mesh migration, chronic inflammation, risk of infection, etc. Injecting a relatively large piece of plastic into the body can also cause a foreign body reaction caused by the body's immune defense system. As a result, the mesh implant may become wrinkled and lose its tissue support function. Another problem is that plastic materials used for meshes, such as polypropylene, have a limited effect on stimulating cell growth. Therefore, cell ingrowth into the defect is often limited, and wound healing is delayed.

[008] On the other hand, fully absorbable (biodegradable) meshes have the advantage that no foreign tissue remains in the body. Some fully biodegradable materials, such as poly-lactic acid (PLA) or collagen, have been shown to promote fibrogenesis, i.e. ingrowth of cells into a soft tissue defect, which is important for rapid and sustainable wound healing. However, if the mesh degrades and resolves too quickly, the scar plaque that gradually builds over the tissue defect will not yet be able to withstand the stresses placed on the repaired soft tissue during daily activities. This is especially important in the case of hernioplasty, since the scar plaque covering the defect must withstand intra-abdominal pressure, otherwise recurrence of the hernia is almost guaranteed. In addition, meshes made from, for example, polylactic acid have the disadvantage that they are quite fragile and tend to break when folded or rolled up for mesh insertion using a laparoscopic instrument.

[009] Thus, the problem solved by the present invention is to provide a mesh implant that allows rapid, safe and stable closure of soft tissue defects, in particular chronic wounds, fistulas or hernia defects. At the same time, the components of the mesh implant must be simple and inexpensive to manufacture and capable of being used using traditional open and laparoscopic surgical techniques.

[0010] This problem is solved using the mesh implant according to claim 1, the production method according to claim 11 and the kit for the implant according to claim 15. Preferred embodiments are the subject of the dependent claims.

[0011] In accordance with the present invention, a mesh implant is provided for use in soft tissue repair, particularly in surgical hernia repair or surgical fistula repair, or in the healing of chronic wounds, in a patient's body. The mesh implant contains a porous hydrophilic biodegradable polymer support mesh made from at least a first polymer containing polylactic acid as a main component. The term "main component" thus means that the content of polylactic acid in the first polymer is higher than the content of any additional polymer that includes the first polymer.

[0012] The polymer support network (which may hereinafter also be referred to as a "support network") has a spongy structure with interconnected pores of different sizes and a contact angle of less than 75°, which means that it is hydrophilic. The mesh implant (which may hereinafter also be referred to as an "implant") according to the present invention further comprises fibroblasts that are present on or within the supporting mesh.

[0013] One of the key elements of the present invention is that the support network is hydrophilic even though it contains, preferably as a major component, poly(lactic acid) (usually abbreviated as "PLA" (polylactic acid) or, in the case of poly-L-lactic acid, "PLLA" (poly-L-lactic acid)), i.e. a biodegradable synthetic polymer that is generally hydrophobic in nature. Through specific processing steps in preparing the support network, which will be described in detail below, the support network can be imparted with hydrophilic properties that are important for promoting cell penetration and adhesion.

[0014] Another key element of the present invention is that the supporting mesh carries fibroblasts. Surprisingly, it has been discovered that the formation of new tissue, especially scar tissue, to close a soft tissue defect can be caused by the introduction of additional fibroblasts (of any origin, eg, autologous, heterologous, xenophilic) into the area of the defect. Thus, rather than focusing on promoting tissue ingrowth, such as smooth muscle cells and fibroblasts, from adjacent tissue into a soft tissue defect, such as a chronic wound, fistula, or hernia, the implant of the present invention utilizes a degradable support mesh so that bring an increased number of fibroblasts to the defect area. Fibroblasts promote the formation of extracellular matrix tissue and collagen fibers of various types, thereby forming a scar plaque that covers the soft tissue defect. In this way, the scar plaque will form a strong connection between the degradable (and therefore temporary) polymer support mesh and the edges of the defect, as well as other surrounding structures (for example, the abdominal wall in the case of an abdominal hernia) to provide the desired supportive function by creating additional scarring.

[0015] For the purposes of this application, the following definitions apply:

[0016] The term "biodegradable" means that the mesh can dissolve over time if placed in a living organism in which it is surrounded by body fluids.

[0017] The term "mesh" as used in this application refers to a three-dimensional support, i.e. to matrix, which means a scaffold or sponge-like structure that is suitable for colonization by cells. In this sense, the mesh serves as a three-dimensional scaffold that can be populated by cells or tissue. This colonization can occur in vitro or in vivo. In addition, in relation to transplantations, the specified mesh serves to determine the location of the graft, and also as a placeholder for tissue that is gradually formed in vivo.

[0018] The term "porous" thus refers to a structure containing pores, i.e. cavities or void areas. These pores may be circular and/or angular in 2D and/or oblique when viewed in 3D. The shape of the pores can also be characterized by extensions so that they can be compared to the shape of nerve cells. Although in general the term "pores" also refers to cavities formed by filaments surrounding void regions, pores within the meaning of the present invention are cavities formed in a three-dimensional sponge structure. Thus, the cavities are closed with walls, as in natural sponges or corals. These pores or cavities may also be interconnected, which means that the pore walls between two adjacent pores may contain openings forming a connection between said adjacent pores. In this regard, it should be noted that pores can also be formed by void regions between hydrogel granules.

[0019] As mentioned above, the polymeric support network according to the present invention has a three-dimensional porous sponge structure containing pores of different sizes. This is different from a knitted mesh construction. At least some of the pores are thereby connected to each other so that they share a space to form a fluid-connected interstitial network. In this way, fibroblasts can spread throughout the mesh structure.

[0020] As used herein, the term “hydrophilic” or “hydrophilicity” as used in the context of the present invention refers to a contact angle of less than 75° of the hydrophilic surface area directly on the support mesh. Preferably, it refers to a contact angle of less than 60°.

[0021] As already mentioned, biodegradable synthetic polymers such as polyglycolic acid or polylactic acid are typically hydrophobic, and the surfaces of porous scaffolds or networks derived from these polymers are therefore typically hydrophobic as well. It has been found that the hydrophilic properties of a polymer network containing polylactic acid as a major component can be improved by post-treatment methods such as plasma treatment (i.e., ionized gas plasma treatment) and/or coating the surface of the porous structure of the framework with a natural polymer such as collagen or gelatin.

[0022] The term "biocompatible polymers" refers to polymers that are biologically tolerable and do not cause rejection when introduced into a living organism. For the purposes of the present invention, biocompatible polymers also include polymers that are recognized by the host as foreign, but whose rejection can be suppressed by appropriate immunosuppression.

[0023] The expression "biodegradable" refers to a material that can be converted into metabolizable products in living organisms (or body fluids or cell cultures derived from living organisms). Biodegradable polymers include, for example, polymers that are self-resorbable and/or bioerodible. "Bioerodible" means the ability to dissolve or suspend in biological fluids. Self-resorbable means the ability to be absorbed by cells, tissues or fluids of a living organism.

[0024] In a preferred embodiment, the polymeric support network has a contact angle of less than 40°, preferably less than 25°, more preferably less than 15°, most preferably the contact angle of the hydrophilic surface of the support network is in the range of 0° to 10°, and, thus, the support network is “superhydrophilic”.

[0025] The term "contact angle" as used throughout the present invention refers to the contact angle of water on a surface, i.e. to the corner formed at the interface where the water comes into contact with the surface. Thus, the “water” used to measure the contact angle refers to pure water, especially ultrapure water. In particular, the contact angle measurement is carried out using the sessile drop method (for example, using a device like EasyDrop DSA20E from Kruss GmbH), using a drop size of 0.3 μl. In general, contact angles are calculated by fitting a circular segment function to the contour of a drop placed on a surface.

[0026] It has been found that a support mesh having hydrophilic properties promotes the ingrowth of tissue, such as smooth muscle cells and fibroblasts, from the adjacent tissue of the hernia defect and ensures an even distribution of cells on and throughout the mesh. In addition, the porous nature of the supporting mesh provides an environment that stimulates the growth of cells that promote the formation of extracellular matrix tissue and collagen fibers of various types, thereby forming a scar plaque that covers the hernia. The formation of a scar plaque will create a strong connection between the degradable (and therefore temporary) polymer support mesh and the edges of the hernia defect, as well as the abdominal wall or other surrounding structures. While decomposition of the supporting mesh continues, the newly formed scar tissue will provide the necessary supporting function by creating additional scarring, thereby preventing the formation of a recurrent hernia. In the end, after complete decomposition of the supporting mesh, i.e. Once the polymer components of the mesh have dissolved, there will be no permanent foreign material left in the patient's body.

[0027] In a preferred embodiment, the support mesh has a flat sheet-like shape and is elastically deformable, allowing it to be folded or rolled. In this embodiment, it is preferable that the support mesh is elastically deformable so that it can be folded or rolled up and can return to its original shape. This allows the rolled or folded mesh to be inserted through the trocar during a laparoscopic procedure.

[0028] If the support mesh is provided in the form of a sheet, it preferably has a thickness of at least 0.1 mm, more preferably at least 0.3 mm, even more preferably from about 1 mm to about 4 mm, in some cases it may be even thicker, for example up to 10 mm.

[0029] If it is provided in the form of a sheet, the cross-section of the supporting mesh can be of any shape, such as rectangular, square, round, oval, etc., and then it can be cut according to the shape of the hernia defect. For example, the overall cross-sectional shape may be round or oval.

[0030] The support mesh may be in the form of one single continuous structure or may also be provided as a plurality of smaller mesh pieces (ie, "flaps") that are separated from each other. These small mesh flaps may be contained in a paste, liquid or semi-liquid formulation.

[0031] In an alternative embodiment, the support network can be provided in the form of a hydrogel, i.e. without a specific three-dimensional outer or transverse shape - the hydrogel, due to its generally hydrophilic nature, promotes tissue growth in the pores, thereby achieving immediate attachment of the load-bearing mesh to the tissue. The hydrogel can also be mixed with other substances such as growth factors or pharmaceutically active substances.

[0032] Regarding the material composition of the support mesh, it is preferable that the support mesh is made of only a first polymer that contains polylactic acid as a main component, or of the first polymer and additionally a natural polymer selected from the group consisting of collagen, gelatin, laminin, fibrinogen, albumin, chitin, chitosan, agarose, hyaluronic acid alginate and mixtures thereof, collagen being preferred.

[0033] Preferably, the sponge structure of the polymeric support network consists of a first polymer and is coated with said at least one natural polymer. If the porous surface of the support mesh is coated or coated with a natural polymer, it is preferable that the underlying porous structure of the support mesh is not altered by the coating. In particular, the pore size is preferably not significantly changed, for example by forming additional networks in the pores of the support network. This ensures that the coating does not negatively impact the ability of fibroblasts to penetrate and spread within the supporting mesh. More details on this are given below in the experimental section.

[0034] In addition, it is preferable that the natural polymer covers substantially all accessible surfaces (except closed-cell surfaces) of the support network. Thus, the cells will spread not only along the upper surface, but also within the porous structure of the supporting mesh.

[0035] Preferably, the first polymer is at least 70% poly(lactic acid), even more preferably at least 80% poly(lactic acid). Polylactic acid was found to have good tensile strength and high elastic modulus. In addition, polylactic acid has been found to be beneficial in achieving and maintaining hydrophilic properties obtained by plasma treatment and/or by coating the polylactic acid structure with a natural polymer such as collagen.

[0036] As used herein, the term "poly lactic acid (PLA)" includes, for example, poly-L-lactic acid (PLLA) or poly-D,L-lactic acid (racemic mixture of L- and D-lactides; poly-D,L-lactic acid, PDLLA). A specific example of a preferred first polymer is poly(L-lactide), which is commercially available from Sigma Corporation (PLLA catalog number P1566) with a molecular weight of 85,000-16,000. A suitable alternative is poly-L-lactic acid from Durect Corporation (Lactel® part number B6002-2).

[0037] In particular, it has been found that for support networks made from a material with a high content of polylactic acid, in particular, if the first polymer consists of more than 50% polylactic acid, for example at least 70% polylactic acid, The hydrophilicity of the surface can not only be significantly improved - for example, by plasma treatment alone or in combination with coating the mesh with a natural polymer, but the hydrophilicity can also be maintained for a long time. In fact, hydrophilicity can also be maintained after sterilization of the carrier mesh with hydrogen peroxide (as will be further described below). This increase in hydrophilicity™ cannot be achieved by plasma treatment of a mesh containing, for example, polyglycolic acid (PGA) as a main component.

[0038] Although the first polymer may consist essentially of pure polylactic acid, it may also be made from a mixture of polylactic acid with other biodegradable materials, such as polyglycolic acid. For example, the first polymer may consist of 75% polylactic acid and 25% polyglycolic acid (based on the weight of the first polymer). One reason for using a mixture of polylactic acid and other biodegradable materials is that meshes made from pure polylactic acid are less resistant to deformation compared to meshes made from polylactic acid mixed with other polymers such as polyglycolic acid (PGA). The abbreviated name for polyglycolic acid is PGA (poly-glycolic acid). Copolymers of polylactic acid and polyglycolic acid - so-called polylactide-co-glycolic acid copolymers (PLGA or PLG, poly-lactide-co-glycolic acid) - are attractive candidates for the production of biodegradable meshes due to their flexible and well-defined physical properties and relative biocompatibility. In addition, their decomposition products are low molecular weight compounds that enter normal metabolic pathways. In addition, PLA-glycolic acid copolymers have the advantage of a wide range of degradation rates from days to years by simply changing the ratio of lactic acid to glycolic acid copolymers.

[0039] In particular, if the mesh implant is intended for use in laparoscopy for minimally invasive surgery, it must be inserted using a laparoscopic instrument such as a trocar. For these applications, the carrier mesh is preferably in the form of a paste or hydrogel, or alternatively in a form that can be elastically folded or rolled for insertion through a laparoscopic instrument. Elastic properties can be achieved through the use of copolymers of polylactide and glycolic acid, i.e. a mixture of polylactic acid and polyglycolic acid as the first polymer.

[0040] Thus, for the foldable support mesh, the first polymer is preferably made from polylactide-glycolic acid (PLGA) copolymers, in particular poly(glycolic acid-lactic acid) having a lactic acid content of about 75 mol. % and glycolic acid content of approximately 25 mol. %). Such a 75:25 poly(D,L-lactide-co-glycolide) material can be purchased, for example, as RESOMER® RG 752 from Evonik Industries AG (Essen, Germany) or from Sigma Corporation PLGA, catalog number P1941. Other preferred polymer blends are poly(D,L-lactide-c-glycolide) 65:35, for example RESOMER® RG 653; poly(D,L-lactide-c-glycolide) 75:25, for example RESOMER® RG 502 from Durect (Cupertino, California, USA); poly(D,L-lactide-c-glycolide) 85:15, for example RESOMER® RG 858 or LACTEL® absorbable polymers.

[0041] Production methods for producing porous networks from the listed synthetic polymers are well known in the art. One possibility is to use salt leaching technology, as described for example in European Patent No. 2256155.

[0042] As already mentioned, in a preferred embodiment, the support network essentially consists of only the first polymer or the first polymer and an additional natural polymer selected from the group consisting of collagen, gelatin, laminin, fibrinogen, albumin, chitin, chitosan, agarose, hyaluronic acid alginate and mixtures thereof. The natural polymer preferably covers all surfaces of the supporting mesh. In this way, the supporting mesh will provide a particularly hydrophilic, cell-friendly environment that increases the survival and rate of cell proliferation on and within the mesh.

[0043] Of the above-mentioned natural polymers, collagen is the most preferred. Collagen is a biomolecule of the extracellular matrix (ECM, extracellular matrix, ECM) and is a major component of skin and bones. Due to its nanofibrous architecture, collagen is particularly effective in promoting cell adhesion, growth, and differentiated function in tissue cultures. However, it has also been found that if the natural polymer contains collagen, the hydrophilic properties of the support network according to the present invention are particularly improved. In this regard, the term "collagen" as used in the context of the present invention covers naturally occurring collagens and synthetically produced collagens, as well as collagen-derived substances such as gelatin, which is a hydrolyzed form of collagen.

[0044] In a preferred embodiment, the natural polymer consists essentially of collagen. In this regard, a natural polymer can consist of only one type of collagen, i.e. type I, or may consist of a mixture of collagen types, such as a mixture of type I collagen and type IV collagen. In the latter case, preference is given to a mixture containing approximately equal mass percentages of proteins. Type I collagen is the most preferred because it is readily available, has a high degree of biocompatibility and provides additional tensile strength. In addition, it is one of the main components of natural blood vessels and provides a natural site of attachment for cells involved in the wound healing process. Finally, the degradation product of collagen types I-III has been shown to induce chemotactic attraction to human fibroblasts, which is particularly useful for the proposed use of the carrier mesh as a fibroblast-containing implant.

[0045] Another advantage of the implant of the invention is the ability to incorporate agents into the supporting mesh and subsequently deliver them to the wound site that affect cell growth, such as collagen types IV and V, fibronectin, laminin, hyaluronic acid and proteoglycans. Likewise, pharmacologically active substances such as epidermal growth factor, platelet-derived growth factor, transforming growth factor beta, angiogenesis factor, antibiotics, antifungals, spermicidal agents, hormones, enzymes and/or enzyme inhibitors can also be included in the carrier network.

[0046] With regard to the decomposition of the support mesh in the body - which usually occurs as a result of bioabsorption of its components - it is preferable that the total decomposition time in a living body is from 1 to 12 months, preferably from 1 to 8 months, more preferably from about 1 to 6 months, most preferably about 2 to 4 months.

[0047] Therefore, to promote the formation of scar tissue, it is preferable that the support mesh further contains growth factors, preferably selected from the group consisting of interleukins, acidic fibroblast growth factor, basic fibroblast growth factor, epidermal growth factor, insulin-like growth factor, insulin-like growth factor growth factor, platelet-derived growth factor, transforming growth factor alpha, transforming growth factor beta, vascular endothelial growth factor and hepatocyte growth factor. These growth factors are important for regulating cell proliferation and differentiation, protein synthesis, and ECM (extracellular matrix) remodeling. In particular, basic fibroblast growth factor, platelet-derived growth factor, vascular endothelial growth factor, and hepatocyte growth factor have been shown to increase granulation, epithelialization, and capillary formation through the secretion of angiogenic cytokines. They have also been shown to inhibit the migration of neutrophils and macrophages to the wound site by secreting factors that inhibit migration and suppress both IL-1α and IL-1β, and also secrete anti-inflammatory factors that prevent apoptosis and improve wound healing.

[0048] Preferably, growth factors are added to the support network along with the placental mesenchymal secretome. One preferred commercially available secretome is a secretome containing Wharton's jelly stem cells (CM-hWAO) that have been cultured under hypoxic conditions. This stem cell secretome can be obtained from the Institute of Stem Cells and Cancer (RT. Kalbe Farma Tbk.). The secretome is used to stimulate the growth of implanted cells on the supporting mesh. Considering its application as a medical device, secretome addition can be applied extracorporeally in an incubator to stimulate cell growth prior to implantation. Once sufficient cell growth has been achieved, the mesh can be flushed with the required media prior to implantation.

[0049] The use of a secretome containing Wharton's jelly stem cells (CM-hW JSC), which were cultured under hypoxic conditions to stimulate cell growth, has proven to be highly effective not only in stimulating fibroblasts, but also in other cells, in particular cells that are more sensitive to processing and cultivation, such as liver cells (hepatocytes). In fact, hepatocytes are commonly co-cultured with pancreatic cells, particularly islet cells of Langerhans, as this has been shown to increase the survival and proliferation rate of hepatocytes. When the mentioned secretome was added to hepatocytes in culture media, the growth and proliferation of hepatocytes were even better than when co-cultured with cells of the islets of Langerhans.

[0050] The fibroblasts provided on the support mesh are preferably autologous fibroblasts from the patient to whom the implant is intended to be installed. Thus, the risk of an unwanted immune response to the patient due to the implantation of foreign cellular material is significantly reduced.

[0051] The present invention also relates to the method for producing a mesh implant described above through the following steps:

a) providing a biodegradable polymer support network as described above;

b) plasma treatment of the polymer carrier mesh with oxidized gas plasma at a temperature below 50°C and

c) inoculating the polymer support network with fibroblasts.

[0052] Plasma treatment has been found to enhance the hydrophilic properties of the surface without adversely affecting the stability or structural integrity of the supporting mesh. Tests showed that plasma treatment was particularly effective in enhancing as well as maintaining hydrophilic properties if the polymer support network had a high polylactic acid content, i.e. contained polylactic acid as the main component. On the other hand, plasma treatment of meshes with polyglycolic acid did not lead to a significant increase in hydrophilicity.

[0053] The ionized gas plasma used for plasma treatment is preferably selected from the group consisting of helium, argon, nitrogen, neon, silane, hydrogen, oxygen, and mixtures thereof. The preferred treatment gas is oxygen.

[0054] The plasma treatment preferably includes a low pressure plasma treatment in which the support mesh is exposed to an ionized gas plasma at a temperature below 50°C, preferably below 40°C. The pressure is preferably in the range from 10 ^-2 to 10 ^-6 bar, preferably in the range from 0.1 to 1.0 mbar.

[0055] The preferred treatment time is at least one minute, preferably 2 to 30 minutes, more preferably 5 to 20 minutes.

[0056] Thus, the term "plasma" generally refers to an excited and radical-containing gas, i.e. to an electrically conductive process gas including electrons and ions. Plasma is typically generated through electrodes in a vacuum chamber (the so-called "high frequency plasma approach"), but it can also be generated using capacitive or inductive methods or microwave radiation.

[0057] More preferably, a method for producing an implant as described above includes the steps

a) providing a biodegradable polymer support network as described above;

b) coating at least the surface of the polymeric support network with a natural polymer, preferably collagen;

c) plasma treatment of the polymer carrier mesh with oxidized gas plasma at temperatures below 50°C and

d) inoculating the polymer support network with fibroblasts.

[0058] It has been found that coating the polymer carrier network with a natural polymer, in particular collagen, also enhances the hydrophilic properties of the surface of the network and is very useful from the point of view of using the carrier network as a carrier for cell proliferation.

[0059] It is particularly preferred that, prior to inoculation with fibroblasts, the polymeric support network is sterilized by treating it with H ₂ O ₂ at a temperature below 50°C.

[0060] The sterilization step according to the production method disclosed in the present invention is highly preferred for obtaining the implant according to the present invention. Surprisingly, it has been discovered that sterilization using hydrogen peroxide provides perfect sterilization of the carrier mesh without the use of any traditional sterilization methods including hot steam, gamma rays, electron beam irradiation or harsh chemical treatments, which have been shown to cause changes or even destruction of the molecular structure of the polymer support network and, therefore, not only reduces its mechanical and enzymatic resistance, but also reduces its hydrophilic properties. In addition, the hydrogen peroxide sterilization method of the invention preserves any collagen layer that may be provided on the support mesh. Unlike traditional sterilization methods, which result in denaturalization of the collagen layers, particularly in the case of nanothick collagen layers, treatment with H ₂ O ₂ as described above does have this degrading effect.

[0061] Sterilization time is highly dependent on the temperature and pressure inside the chamber and the concentration of the H ₂ O ₂ solution. The H ₂ O ₂ solution preferably contains H ₂ O ₂ in an amount of about 30% by volume or less. The preferred treatment time is at least one minute, preferably at least 5 minutes or at least one hour. When "higher" pressures (eg about 10 mbar) and low temperatures (eg below 40° C.) or H ₂ O ₂ concentrations of less than 30 vol.% are used, treatment times of up to 10-12 hours may be appropriate.

[0062] The hydrogen peroxide containing medium can be produced either by treatment with H ₂ O ₂ plasma or by placing the substrate to be sterilized in a vacuum chamber along with a source of (usually liquid) hydrogen peroxide. When a vacuum is applied inside the vacuum chamber, the hydrogen peroxide sublimates and an atmosphere containing hydrogen peroxide is created. Moreover, the negative pressure applied in the vacuum chamber is preferably in the range of 10 ^-6 to 10 ^-2 bar, more preferably 0.1 to 20.0 mbar, for example about 9 mbar.

[0063] To promote the wound healing process, the method described above preferably includes an additional step in which a secretome containing growth factors, in particular a mesenchymal secretome, is introduced onto or into the supporting mesh.

[0064] The present invention also relates to the use of the mesh implant according to the present invention in the closure of a primary wound, for example after a primary abdominal incision, in order to promote wound healing, especially in the case of chronic wounds and scarring processes. In addition, it is also well suited for use in the closure of fistulas or hernias.

[0065] In an additional aspect, the present invention also relates to a method of closing a hernia using an implant as described above. In general, during this method, a degradable polymer support mesh seeded with fibroblasts will be placed over a defect such as the abdominal wall (Lichtenstein inguinal hernia repair), under the muscular layer of the abdominal wall (sublay technique), as an IPOM repair, or in any technique that the surgeon may deem it suitable for plastic surgery.

[0066] In addition to hernias, the mesh implant of the present invention is also particularly suitable for the surgical closure of fistulas. A fistula is a junction lined by epithelial tissue that pathologically connects the intra-abdominal space to the skin, having an opening at the level of the skin - often causing fluid to leak through the skin - or an pathological connection between the large or small intestine and the anal area. Fistulas are difficult to treat surgically and are prone to recurrence. To this day, complete resection of the entire fistula is the preferred therapy. Various materials have been developed that can be inserted into the resected canal to improve the healing process. None of them have proven to guarantee long-term success. However, insertion or implantation of a fibroblast-bearing mesh, as described above, has been found to significantly enhance the healing process. This effect has also been observed in chronic wounds and fistulas. In this regard, in accordance with the above description, the supporting mesh may be sheet-shaped or may not have a specific geometric shape when implemented in the form of a paste or hydrogel.

[0067] The present invention also relates to a kit for use in the surgical repair of soft tissue, in particular in the treatment of fistulas or hernia repair, in the body of a patient, the kit comprising a) a polymeric support mesh as defined above, and b) an additional, preferably biodegradable, a support mesh having a lower decomposition rate than a polymer support mesh.

[0068] If the support mesh is biodegradable, it preferably has a degradation rate in the range of 4 to 12 months.

[0069] The non-degradable or degradable support mesh is designed to be placed under the polymer support mesh to cover the hernia after the polymer support mesh has degraded. This means that in general the support mesh will provide additional support after the first three months.

[0070] In a preferred embodiment, the support mesh is biodegradable and decomposes in at most 12 months. Like the support mesh, the support mesh is preferably at least partially hydrophilic and thus promotes the formation of a scar plaque overlying the hernia.

[0071] Most preferably, the support mesh is a conventional commercially available mesh.

[0072] In a preferred embodiment, the polymer support network comprises one or more polymers selected from the group consisting of poly(glycolic acid), poly(lactic acid), poly(glycolic acid-lactic acid), and mixtures thereof. Moreover, in this embodiment, if both the polymeric support mesh and the support mesh are biodegradable, then the support mesh preferably has a higher decomposition rate than the support mesh.

[0073] In another preferred embodiment, the kit includes, as a support mesh, an additional two-layer release mesh, which contains two separate or integral layers consisting of

i) a hydrophilic layer facing the peritoneum or exposed muscle tissue or fascia of the abdomen and having a contact angle of less than 75°, preferably less than 60°, and

ii) a hydrophobic layer having a contact angle greater than 90°.

[0074] This embodiment of the implant kit provides two main advantages: on the one hand, the polymer support mesh provides temporary closure of the defect, in particular a hernia or fistula, while fibroblasts form new scar tissue that will take over the supporting function of the support mesh after its decomposition. On the other hand, the two-layer anti-adhesion mesh, which functions as a support mesh, has a top layer with hydrophilic properties that will promote tissue growth on the side facing the soft tissue defect, in particular the proliferation of implanted fibroblasts that help form the scar plaque ultimately covering the defect, and a lower layer with hydrophobic properties that prevent the attachment of various cells, in particular inflammatory cells, fibrin or debris, to the anti-adhesive mesh on the intraperitoneal side, i.e. on the side of the supporting mesh, facing away from the defect, in such a way that inflammation occurs and the growth of adhesive tissue occurs between the anti-adhesive mesh or the newly formed scar plate and the underlying tissues of the abdominal cavity.

[0075] Although the support mesh as a whole is said to have a slower decomposition rate than the support mesh, it may also be the case that portions of the support mesh have a degradation rate similar to the decomposition rate of the support mesh. For example, in an embodiment in which the support mesh has a top and a bottom layer as defined in the previous paragraphs, the top layer may have a faster decomposition rate than the bottom layer such that, for example, the decomposition time of the top layer in a living body is between 1 up to 3 months, preferably about 2 months, and the decomposition time of the lower layer in a living body is from 4 to 8 months, preferably about 6 months. This means that in this two-layer embodiment, it is the bottom layer of the support mesh that provides the additional support function for the first four to eight months. After this time, the bottom layer will also preferentially decompose.

[0076] Given their use in hernia repair or fistula repair surgery, it is preferred that at least one, preferably both the polymeric support mesh and the support mesh have/have flexibility that allows it/them to be inserted into the patient's body through a laparoscopic instrument.

[0077] Each of the resin support mesh and the support mesh can be provided in any shape, for example, rectangular, square, round, oval, etc., and then it can be cut according to the shape of the hernia defect. For example, the overall shape of the mesh may be round or oval. Alternatively, the grids may be generally square or rectangular in shape. As yet another alternative, the support mesh may have a flat sheet-like shape and the support mesh is in the form of a paste or hydrogel containing or containing fibroblasts. In this way, the support mesh will hold the load-bearing mesh in place while the load-bearing mesh can be used to fill the soft tissue defect.

[0078] The implant kit of the present invention, when used to close a hernia, can be used as follows:

[0079] First, an implant kit is provided as described above. An incision is then made through the patient's skin and tissue to gain access to the defect in the peritoneum. A polymer support mesh is then placed either over a defect such as the abdominal wall (Lichtenstein inguinal hernia repair), or alternatively under the muscular layer of the abdominal wall (sublay technique), or as an IPOM (intraperitoneal on lay mesh) below the peritoneum before placing the polymer support mesh on top of the support mesh. If the support mesh is provided in the form of a sheet, it can be further attached to the abdominal muscles. The incision is then closed.

[0080] The hernia defect usually closes with a scar plaque within 3-6 months, during which time the biodegradable support mesh gradually loses its strength and consistency. Eventually, there will be no permanent foreign material left when the mesh components are bioabsorbed into the body.

Experimental data

Obtaining a supporting mesh

[0081] The sodium chloride (NaCl) solids were ground using a mortar and pestle before sieving to obtain NaCl particles ranging in size from 355 to 425 μm. 9 g of NaCl particles were placed in a centrifuge tube and dried in a desiccator. The NaCl particles were then placed in an aluminum pan.

[0082] A poly-L-lactic acid solution prepared from 1 g of poly-L-lactic acid granules dissolved in 5 ml of chloroform was mixed with NaCl particles, and then the mixture was evenly distributed in an aluminum pan to form a flat layer of poly-L-lactic acid. lactic acid. The solvent was allowed to evaporate by air drying at room temperature for 20 to 48 hours, preferably 24 to 36 hours, most preferably 28 to 32 hours. Alternatively, solvent evaporation was carried out in a temperature-controlled oven placed in a fume hood to extract chloroform toxic gases.

[0083] The pre-dried poly-L-lactic acid-NaCl layer was separated from the aluminum tray and dried in a vacuum chamber at a negative pressure of 0.1 MPa for 3-4 days.

[0084] The resulting dried poly-L-lactic acid-NaCl layers were placed in a beaker and the NaCl particles were leached by rinsing the matrices with deionized water. To do this, the matrices were immersed in ddH ₂ O (twice denominated water) and kept in a linear shaking bath at 25°C (room temperature) at 60 rpm for 48 hours. The water in the beaker was changed every 1-2 hours. The poly-L-lactic acid meshes thus obtained were removed from the beaker and dried in a fume hood overnight.

Post-treatment with collagen

[0085] Poly-L-lactic acid meshes were cut into a circular shape with a diameter of 1 cm. Each poly-L-lactic acid mesh was then immersed in an acidic solution of type I collagen (1.0 (w/v)% , pH 3.0, purchased from Wako) under vacuum so that the pores of the mesh were filled with collagen solution. To remove any excess collagen solution in the poly-L-lactic acid meshes, they were placed in a centrifuge tube and centrifuged for 10 min at 2000 g. Accelerations greater than 600 g were found to promote the formation of collagen-coated poly-L-lactic acid networks rather than the formation of collagen microsponges in the pores.

[0086] The collagen-poly-L-lactic acid mesh was then frozen at -80°C for 12 hours and lyophilized under <5 Pa vacuum for an additional 24 hours to remove any solvent from the mesh.

[0087] If a cross-linker was used (which was found to be unimportant for the production of the mesh), the collagen-poly-L-lactic acid mesh was further cross-linked by treating with glutaraldehyde vapor saturated with a 25% aqueous glutaraldehyde solution at 37°C for 4 hours. After cross-linking, the network was treated with a 0.1 M aqueous solution of glycine to block unreacted aldehyde groups. Other blocking agents may be used in place of glycine, such as casein, albumin, gelatin, or methanol-acetic anhydride. After washing with deionized water and lyophilization, the polymer support network was obtained as the final product. After freeze-drying (also known as freeze-drying), the collagen-poly-L-lactic acid meshes were stored in a desiccator until use.

[0088] The support meshes have been prepared with pores having diameters ranging from 50 to 900 micrometers, preferably from 280 to 560 micrometers, most preferably from 355 to 425 micrometers.

[0089] Notably, the pores in the poly-L-lactic acid networks had essentially the same shape as the NaCl particles. Collagen coating of poly-L-lactic acid meshes thus changed only the surface wettability (hydrophilicity) but did not change the pore structure.

[0090] Compared to uncoated poly-L-lactic acid meshes, collagen-coated poly-L-lactic acid meshes demonstrated both improved wettability and high water absorption.

O ₂ plasma treatment

[0091] The support meshes, whether collagen-coated or not, are optionally subjected to plasma treatment using an ionized gas plasma, preferably selected from the group consisting of helium, argon, nitrogen, neon, silane, hydrogen, oxygen, and mixtures thereof. Preferably, plasma treatment using ionized oxygen, hydrogen or nitrogen gas was used.

[0092] Plasma treatment was carried out using a plasma treatment device from Diener (Diener electronics; Plasma-Surface-Technology; Ebhausen, Germany) in a vacuum chamber for a period of time from 5 to 20 minutes, preferably from 8 to 15 minutes. The following processing parameters were set: pressure in the vacuum chamber: 0.40 mbar; power: 35 W; oxygen gas flow: 5 cm ³ /min (min.) - 60 cm ³ /min (max).

Sterilization

[0093] Finally, the support meshes were further sterilized by placing them in an environment containing H ₂ O ₂ by exposing the support mesh to an atmosphere containing H ₂ O ₂ .

[0094] An environment or atmosphere containing H ₂ O ₂ was created within the vacuum chamber by placing a support mesh in the chamber along with an open flask containing a solution of H ₂ O ₂ and then evacuating the chamber to evaporate the H ₂ O ₂ . The H ₂ O ₂ solution contained H ₂ O ₂ in an amount of 30% by volume. The processing time strongly depends on the pressure inside the chamber and the concentration of the H ₂ O ₂ solution. Preferably, the sterilization time was from 10 to 12 hours at a temperature of 40° C. and a pressure of about 9 mbar. However, at lower pressures or higher temperatures, processing times of only a few minutes have also proven effective.

Static contact angle measurements, sessile drop method

[0095] Contact angle measurements were performed to determine the degree of hydrophilicity or hydrophobicity. Typically, the contact angles of meshes were determined by static contact angle measurements. Static contact angles were determined using the sessile drop method with ultrapure water (EasyDrop DSA20E, Krtiss GmbH). 0.3 μL water droplets were dispensed using an automated unit. Contact angle values were calculated by fitting a circular segment function to the contour of a drop placed on the surface.

Collection, cultivation and seeding of fibroblasts

[0096] Fibroblast collection was performed by dermatological or surgical excision of a full-thickness skin sample under strict sterile conditions measuring approximately 2 cm x 1 cm. The sample was placed in a sterile container and covered with pre-warmed phosphate buffered saline containing 2% antibiotic/antimycotic (AB). /AM). The sample was transported to the laboratory where it was washed with a pre-warmed wash solution/ethylene glycol tetraacetic acid solution containing 2% AB/AM. The washed skin sample was covered with freshly prepared 200 U/ml collagenase in complete Dulbecco's modified Eagle's minimal essential medium (DMEM, Dulbecco's minimal essential medium), containing 10-20% fetal bovine serum, 2% AB/AM, 2 mM L-glutamine and 1 mM Na-pyruvate solution, and then incubated from the dermis side down - at 37 ° C, 5% CO ₂ within 3-5 hours. The lateral portion of the dermis was gently scraped using a cell scraper until the entire portion of the dermis was dissolved in the collagenase solution. Part of the epidermis was discarded, the cell suspension was sieved through a 100-μm nylon sieve, and the cells collected on the sieve were washed thoroughly with fetal bovine serum (2% AB/AM) before collection in a centrifuge tube. Cells were centrifuged for 10 minutes, the supernatant was discarded, and the cells were resuspended in complete DMEM containing 10–20% FBS, 2% AB/AM, 2 mM L-glutamine, 1 mM Na-pyruvate, and 10 mM N-2-hydroxy- ethylpiperazine-N-2-ethanesulfonic acid (HEPES). The resuspended cells were placed in a collagen-coated flask and incubated at 37°C, 5% CO ₂ for 30 minutes. Fibroblasts attached to the collagen-coated surface of the flask were separated from non-fibroblasts remaining in the culture medium. Cell counts were performed using triptan blue staining.

[0097] When necessary, fibroblasts were incubated in DMEM. The supporting mesh was seeded with fibroblasts (500,000 cells per 1 ^cm2 ).

[0098] It has been found that the collagen coating increases the wettability of the porous surface of the support mesh and promotes the penetration of the cell suspension solution, which allows fibroblasts to easily penetrate into the internal pores of the support mesh.

[0099] Preferred embodiments with respect to the structure of the implant according to the invention and its placement in the patient's body for soft tissue reconstruction are further described in connection with the accompanying figure, in which

[00100] in FIG. 1 is a schematic representation of a cut through a soft tissue defect repaired using a kit in accordance with the present invention.

[00101] In the schematic diagram of FIG. 1 shows a defect (gap) in muscle tissue 12 that has been filled with a mesh implant 10 according to the present invention. Specifically, a commercially available support mesh 14 was placed under the defective muscle tissue 12 before a polymeric biodegradable support mesh 10 containing fibroblasts 16 was inserted into the defect. The overlying skin 17 was then repaired, i.e. closed with sutures 18. The supporting mesh provides a temporary support structure for the proliferation of fibroblasts and for the growth of cells from adjacent tissues. In general, the support mesh 10 containing the fibroblasts 16 will simply be inserted into the defect or placed over the defect. Thanks to the supporting mesh 14, displacement of the supporting mesh 10 from the implantation site is prevented.

[00102] For several days and weeks after insertion of the mesh implant, fibroblasts applied with the load-bearing mesh within the muscle tissue defect continued to proliferate and spread into adjacent tissues. This is indicated by fibroblasts that have spread into the adjacent muscle tissue and supporting meshwork underneath the defect. The foreign fibroblasts have been shown to produce collagen, which helps build up scar tissue that tightly seals the defect in the muscle tissue while the supporting mesh completely degrades.

[00103] The mesh implant of the present invention has also been tested in vivo in rats, as will be described in the following sections.

Histology

[00104] An experimental abdominal wall hernia in a rat was repaired using a biodegradable mesh implant in accordance with the present invention, i.e. through a supporting mesh carrying fibroblasts. In this experiment, a hernia in the abdominal wall muscle tissue was filled with a support mesh according to the invention, carrying numerous fibroblasts, and a secretome added to the support mesh. To hold the implanted support mesh in place, two additional support meshes were implanted, one above and one below the hernia in the muscle tissue and an additional support mesh as part of the inventive kit described above. Histological analysis of the skin wound site is shown in Fig. 2-6A:

[00105] in FIG. 2 is a top view of an excised portion of the abdominal wall, including a former hernial area, which has been repaired using a kit according to the present invention, including a fibroblast-bearing mesh and an additional support mesh;

[00106] in FIG. 3A shows a section through the abdominal wall of FIG. 2 along line A, i.e. through the former hernial area;

[00107] in FIG. 3B, 3C show enlarged detail sections of FIG. 3A with magnification 40x and 200x, respectively;

[00108] in FIG. 4A shows a section through the abdominal wall of FIG. 2 along line B, i.e. near the former hernial area;

[00109] In FIG. 4B shows an enlarged detail section of FIG. 4A with 40x magnification;

[00110] In FIG. 5A shows a section through the abdominal wall of FIG. 2 along line C, i.e. at a distance to the former hernial area; And

[00111] In FIG. Figure 6 shows an enlarged, detailed section at 40x magnification through the abdominal wall of a comparative example in which the hernial area was repaired using a fibroblast-free support mesh.

[00112] As shown in FIG. 2, the abdominal wall includes layers of epidermis 20, dermis 22, subcutaneous tissue 24 with fat cells, muscle tissue 26 and, within the muscular region 26, a former hernial region 28 into which a load-bearing mesh and a support mesh have been implanted. Thus, the former gap in muscle tissue 26 was filled with a supporting mesh (and fibroblasts).

[00113] In FIG. 3A-3C show an enlarged view of the former hernial area 28. Within this area 28 is visible a tissue mass 29 that fills the former hernia and consists at least in part of a partially decomposed load-bearing mesh 10. Within this mass 29 a population of mesenchymal-like cells ( elongated and round cells) 32, located in intertwined woven ligaments, as well as stellate spindle-shaped fibroblasts 16 with a relatively clear border and oval flat nuclei with fine-grained chromatin. The mesenchymal cells 32 are believed to originate from a secretome that was deposited on the supporting mesh along with fibroblasts 16. Collagen fibers 38 are mixed with the mesenchymal cells 32. Adipose tissue 30 is visible below the mass 29 of fibroblasts/collagen/mesenchymal-like cells. Above mass 29, an area of reepithelialization 40 is visible, which separates mass 29 from several layers of epithelial cells with orthokeratotic hyperkeratosis and intracorneal reepithelialization of pustular cells. The remains of the support mesh 14 can be observed below the mass 29 at the border of the muscle region 26 with the adipose tissue 30 (Fig. 3C).

[00114] Typically, fibroblasts are found in much smaller numbers and mainly in the subcutaneous area. The large number and arrangement of identified cells strongly implies that these stellate spindle-shaped fibroblast cells 16 originate from the implanted scaffolding mesh 10.

[00115] Confirmation of the above findings is shown in FIG. 4A-6A: In FIG. 4A and 4B show a section through the repaired abdominal wall shown in FIG. 3A-C, however, the incision was made not through the former hernia 28, but next to it. In this adjacent area, only the support mesh 14 is present, as it is sized to cover not only the hernial area 28, but also the areas adjacent to and around it. The support mesh 14 is still clearly visible above and below the muscle area 26. Unlike the sections shown in FIG. 3A-3C, there is no supporting mesh.

[00116] On the other hand, in FIG. 5A shows a cut through the tissue at a distance from the hernial area, i.e. through normal tissue of the abdominal wall. As expected, there is no support grid or any kind of load-bearing grid.

[00117] In FIG. 6A shows the results of a control experiment in which a scaffolding mesh 10 without fibroblasts was implanted to close a soft tissue defect in the abdominal wall of a rat. This control experiment confirmed that the stellate spindle cells identified in the tissue sections shown in FIG. 3A-3C (and absent in Fig. 6A) are fibroblasts, from which tissue is not produced. Thus, the histological results confirm that the presence of fibroblasts is not due to normal wound healing processes and inflammation, but to the fact that fibroblasts arise as a result of implantation. In addition, it was found that fibroblasts introduced into a soft tissue defect using the mesh implant according to the invention not only remain in place of the supporting mesh, but also actively migrate into the adjacent nourishing tissue, where they support the formation of collagen, which is believed to ultimately leading to improved scar formation.

[00118] Thus, histological analysis not only confirmed the distribution of implanted fibroblasts within the soft tissue defect and within the supporting mesh, but also showed ingrowth and migration of fibroblasts into adjacent tissues.

Claims (35)

1. A biodegradable mesh implant for use in soft tissue repair, chronic wound healing or surgical fistula healing in a patient's body, wherein the mesh implant contains porous hydrophilic biodegradable polymer support mesh and fibroblasts on or within a polymer support mesh, wherein the supporting mesh contains a sponge structure with interconnected pores of different sizes, has a contact angle of less than 75° and made from at least a first polymer containing polylactic acid as a main component, wherein the polymer support network is subjected to plasma treatment and/or the sponge structure of the polymer support network is coated with at least one natural polymer. 2. The implant of claim 1, wherein the polymer support network has a contact angle of less than 40°, preferably less than 25°, more preferably less than 15°, most preferably in the range from 0° to 10°. 3. The implant according to claim 1 or 2, in which the supporting mesh has a flat sheet-like shape and is elastically deformable, which allows it to be folded or rolled up. 4. Implant according to one of paragraphs. 1-3, wherein the first polymer consists of at least 70% poly(lactic acid), more preferably at least 80% poly(lactic acid), or substantially consists of poly(lactic acid). 5. Implant according to one of paragraphs. 1-4, in which the polymer support network consists of only the first polymer or of the first polymer and at least one natural polymer selected from the group consisting of collagen, gelatin, laminin, fibrinogen, albumin, chitin, chitosan, agarose, hyaluronic alginate acids and mixtures thereof, with collagen being preferred. 6. The implant according to claim 5, in which the spongy structure of the polymer supporting mesh is covered with collagen. 7. Implant according to one of paragraphs. 1-6, wherein the supporting mesh has a total in vivo decomposition time of 1 to 12 months, preferably 1 to 8 months, more preferably about 1 to 6 months, most preferably about 2 to 4 months. 8. Implant according to one of paragraphs. 1-7, in which the fibroblasts are autologous fibroblasts from the patient to whom the implant is intended to be installed. 9. Implant according to one of paragraphs. 1-8, further comprising growth factors preferably selected from the group consisting of interleukins, acidic fibroblast growth factor, basic fibroblast growth factor, epidermal growth factor, insulin-like growth factor, insulin-like growth factor binding protein, platelet-derived growth factor, transforming growth factor alpha, transforming growth factor beta, vascular endothelial growth factor and hepatocyte growth factor. 10. The implant of claim 8, wherein the growth factors are growth factors in the mesenchymal secretome of the placenta. 11. Method for producing a mesh implant according to claims. 1-10 via a) providing a biodegradable polymeric support network containing a sponge structure with interconnected pores of different sizes, having a contact angle of less than 75° and made from at least a first polymer containing polylactic acid as a main component; b) plasma treatment of the polymer carrier mesh with oxidized gas plasma at a temperature below 50°C and c) inoculating the polymer support network with fibroblasts. 12. The method according to claim 11, including the steps a) providing a biodegradable polymeric support network made from a first polymer comprising a sponge structure with interconnected pores of different sizes, having a contact angle of less than 75° and made from at least a first polymer containing polylactic acid as a main component; b) coating at least the surface of the polymeric support network with a natural polymer, preferably collagen; c) plasma treatment of the polymer support mesh by treating the polymer support mesh with oxidized gas plasma at a temperature below 50°C and d) inoculating the polymer support network with fibroblasts. 13. Method according to one of paragraphs. 11 and 12, according to which, before inoculation with fibroblasts, the polymer carrier mesh is sterilized by treating it with H ₂ O ₂ at a temperature below 50°C. 14. The method according to claim 13, according to which the sterilization step is carried out by treating the polymer carrier mesh with H ₂ O ₂ plasma or by exposing the carrier mesh to an atmosphere containing H ₂ O ₂ at a pressure in the range from 10 ^-2 to 10 ^-6 bar , preferably in the range from 0.1 to 20.0 mbar, for at least 1 minute, preferably at least 5 minutes. 15. Method according to one of paragraphs. 11-14, further comprising the step of adding a secretome containing growth factors to the support mesh. 16. An implant kit for use in surgical repair of wounds in a patient's body, wherein the implant kit includes mesh implant, including a biodegradable polymer carrier mesh carrying fibroblasts, according to one of paragraphs. 1-10 and a polymer support network containing one or more polymers selected from the group consisting of poly(glycolic acid), poly(lactic acid), poly(glycolic acid-lactic acid) and mixtures thereof; and The polymer support mesh has a higher decomposition rate than the support mesh. 17. The implant kit of claim 16, further comprising an anti-adhesive mesh comprising two separate or integral layers consisting of a hydrophilic layer facing the abdominal muscle tissue and having a contact angle of less than 75°, preferably less than 60°, and a hydrophobic layer having a contact angle greater than 90°. 18. A kit for an implant according to claim 16 or 17, in which the support mesh has a flat sheet-like shape, and the polymer support mesh is made in the form of a paste or hydrogel containing or containing fibroblasts.