DE102010026322A1 - Medical surgical implant i.e. micro-surgical suturing thread, for repairing tissue damage from living tissue of patient during operation of tissue sections of wound, has hollow filament whose portion comprises filling element - Google Patents

Abstract

The implant i.e. micro-surgical suturing thread, has a hollow filament (10) made of an organic-resorbable and/or biodegradable polymer and comprised of a cladding (14) and two open ends (16a, 16b). A cavity (15) is included between the ends. A portion (12) of the filament is arranged with cells (18), where the cells are arranged on an inner surface and/or outer surface, and the portion comprises a filling element. The filling element is a carrier matrix i.e. collagen matrix. The cells are autologous and/or non-autologous stem cell e.g. autologous human stem cell and differentiated tissue cell. An independent claim is also included for a method for manufacturing a surgical implant.

Description

The invention relates to surgical implants made of bioresorbable and / or biodegradable polymers and to processes for their preparation.

The use of surgical implants made of bioresorbable and / or biodegradable polymers has long been known. For example, biodegradable materials are used as carrier materials for implantation purposes, with polyglycolic acid, polylactite, collagen or gelatin generally being used, since these polymers are broken down and absorbed in a certain period of time. The materials are often used in the form of nets, tissues or individual fibers, for example, to transfer a pharmaceutically active substance into the body of the patient and, in the case of a drug, to achieve a controlled release over a longer period of time.

In addition, it is known to use implants of living tissue for the repair of tissue damage, for which the patient removed during surgery larger tissue sections from healthy, uninjured tissue and these are prepared for wound care, before they are then used as implants the donor again.

Furthermore, the production of human extracellular matrix (ECM) from adipose tissue is known, which is obtained by liposuction and then populated with patient-specific cells and used for implantation. In addition, it is also known to use foreign cells, but here is the problem of the rejection reaction of the implant to get. For example, microfiber nets made of biodegradable polymers, such as polylactite, are used as a carrier material on which live cells are seeded and cultured before implantation. One such already commercially available product is Dermagraf from Advanced BioHealing, Inc., La Jolla, USA.

In addition, biodegradable hollow fibers are known in the art. That's how it describes US 4,965,128 biodegradable hollow fibers having an asymmetric fiber wall, the cavity of which may be filled with a drug such as a drug, a hormone, or the like, in which case the two sides of the hollow fiber are closed and the substrate serves to allow a controlled release of the substances trapped in the hollow fibers ,

Furthermore, the describes DE 10 2008 019 748 A1 an element with a hollow body, wherein the element can be used as an implant. The hollow body consists of bioresorbable magnesium and / or a bioabsorbable magnesium alloy and the filling has a biocomposite material, this biocomposite material having at least one biocompatible polymer component and at least one ceramic component. In addition, the filling of the hollow body and / or the hollow body on its outside bone formation-promoting factors, in particular growth factors, have and the hollow body and / or the filling of a porous material. Such implants are intended to be used in the bone surgery area.

Finally, it is still out of the DE 25 21 793 A1 a T cell filled hollow fiber and its use for performing metabolic processes, but not for use as an implant. In this case, cells are to be deposited on the hollow fiber, wherein the hollow, porous fiber material carries the cells either on the inner or on the outer wall. The hollow fibers serve as a semipermeable membrane.

Basically, medical implants in various forms are known. These may be fasteners for a bone, such as plates, screws or nails, surgical sutures, surgical nets or films, or even prostheses.

The invention now has the task of providing a surgical implant that is degradable or resorbable in the body and offers a variety of uses and is inexpensive to implant.

The invention solves this object by a surgical implant with the features of claim 1, wherein in the cavity of the hollow filament cells are arranged at least in a portion of the hollow filament, wherein the cells provided either on the inner circumferential surface and / or on at least one of the section Filling element are arranged.

In this case, the inner lateral surface or the filling element is populated with the cells. It should also be understood by the term that the cells are arranged on the filling element that the cells are arranged on the surface of the filling element, provided that the filling element has a porous, openwork or otherwise shaped structure with cavities.

Particularly preferably, it is further provided that additives for influencing cell differentiation and / or cell growth are arranged in the cavity, on the inner and / or outer lateral surface and / or the filling. there For example, the additives within a porous structure of the filler may also be provided and anchored thereto.

It can be provided in particular that the cells are autologous and / or non-autologous stem cells, in particular autologous human stem cells or differentiated tissue cells.

In addition to the use as a human medical implant and the veterinary use comes into question.

Stem cells are regarded as great hope carriers in medicine because they have the ability to transform into different cell types of the human body. This property makes them particularly interesting in regenerative medicine, d. H. for the restoration of irreversibly damaged tissue, e.g. B. after a heart attack or complicated bone fractures. The use of so-called adult stem cells, which occur in many human organs, is thereby preferred.

The problem has always been the targeted introduction of stem cells directly into the damaged tissue. Stem cells are currently u. a. applied via the bloodstream with the disadvantage that they can not be placed locally on Gewebsdeffekt. For this reason, one works with so-called scaffolds, so two- or three-dimensional structures made of synthetic or biological materials such. B. autologous ECM or collagen matrices are made. A disadvantage is that the scaffolds have no promoting the differentiation of stem cells property. In addition, the distribution of the stem cells in a three-dimensional structure is possible only inhomogeneous in its outer area and finally the placement of such three-dimensional structures is usually associated with a major surgical intervention.

According to the invention, it should now be provided that cells are arranged in the cavity at least in a section of the hollow filament, wherein the cells are provided either on the inner circumferential surface and / or a filling element arranged in at least the section of the hollow filament. As a result, a sufficiently large number of cells can be arranged in a comparatively small volume relative to the surface of the scaffolds, that is to say of the 2-dimensional and 3-dimensional structures, so that the implant to be implanted can be smaller and therefore less injury to the patient during implantation arises ,

It is particularly preferred that additives for influencing cell differentiation and / or cell growth on the filling element and / or the hollow filament are provided, in particular in the region of the section of the hollow filament in which the cells are arranged. Such additives are in particular differentiation or growth factors for the intended cells and serve in particular to influence the differentiation of the stem cells used to the desired cell type. This combination of cells and additives, in particular stem cells and differentiation factors in an implant represents a novelty and offers particular advantages in terms of targeted cell diffusion at the site of implantation, since all the necessary elements are in place.

In this case, the additives can be arranged both on the inner and on the outer circumferential surface of the hollow filament. Alternatively or additionally, they can also be set on the filling element if provided.

The cells are always located inside the cavity of the hollow filaments, wherein the hollow filaments themselves can be used as a cell carrier. In addition, the cells can also be provided on a filling element.

Depending on the arrangement of cells and additives, the contact of cells with the additives can be influenced. Thus, additives on the outside of the jacket initially possibly interact with the surrounding tissue and interact with the cells arranged in the interior only after the growth or dissolution of the filaments.

The hollow filament can have a cylindrical jacket or a jacket in which the diameter is not constant over the entire length. In particular, the hollow filament can also have an elliptical or angular cross-section. The shell thickness of the hollow filament can be constant or variable over the length.

The openings of the hollow filament at its ends can be closed after filling the cavity or alternatively remain open. It can also be provided that the filled section of the hollow filament is closed with respect to its ends, but the ends of the hollow filament projecting beyond the section remain unclosed. Insofar as the cells are enclosed in the cavity by closing the ends of the portion of the hollow filament or hollow filament, they can not contact the environment until the hollow filament dissolves, thereby achieving a sustained release. If pores are provided in the hollow filament, contact with the environment after insertion is initially only possible over these until the hollow filaments dissolve.

Suitable filling elements are a carrier matrix, in particular a collagen matrix, but also other corresponding porous materials which offer the largest possible surface area for cell colonization and for the arrangement of additives. Here are glycosaminoglycans, such as. B. hyaluronic acid. These may also be linked to proteins, preferably adhesion proteins, to proteoglycans. The carrier matrix may consist of glycoproteins, as well as of high-chain polysaccharides.

In this case, the lateral surface of the hollow filament may have pores for the passage of the cells, at least in the filled filament section. The pores have a size of preferably 1 to 1000 .mu.m, in particular from 1 to 500 .mu.m and in particular from 1 to 20 microns. The pores may have any shape, but are preferably round or oval.

The implant may preferably be a microsurgical suture. In addition, it can be provided that the hollow filaments are connected to two- or three-dimensional structures, which can then be brought via a surgical procedure to the place where the stem cells want to intervene to repair. The structures can have any desired shape and size.

A corresponding microsurgical suture or a corresponding two- or three-dimensional structure can then be placed by the surgeon exactly in the damaged tissue. In this case, the thread section in addition to the stem cells or differentiated tissue cells additionally contain the required differentiation factors or other additives which ensure after microsurgical intervention that the desired target cells arise. The tissue regeneration then finds purposeful and controlled in situ, d. H. in the patient's body.

By providing the cells in the desired location, negative clinical side effects, such as excessive, uncontrolled reactions such as may occur in stem cell injections into the bloodstream, can be avoided. The simultaneous presentation of defined differentiation factors or other additives creates the desired target cells in a timely and controlled manner.

In contrast to the use of in particular three-dimensional structures (scaffolds), when using a microsurgical suture as an implant, the patient only needs a microsurgical procedure for positioning the suture, whereby the suture can remain in the body and dissolve in the body after a predetermined period of time. It can be provided by the filling of the hollow filament comparatively large cell counts in or on the implant, so that even when connecting the hollow filaments to 2- or 3-dimensional structures such. As networks or bodies these Struturen (scaffolds) can be kept smaller than previously possible. In particular, however, even when using a short suture, a sufficient number of cells and, if desired, can be introduced together with helpful or necessary additives.

The hollow filament can be formed from bioresorbable and / or biodegradable polymers which are selected from polylactides (PLA, PLLA), polyglycolic acid (PGA), glycolide / lactide copolymers (PLGA), polydiaxonones. Also conceivable are biopolymers of nucleic acids, proteins or polysaccharides.

It is provided that the filling of the hollow filament or the application of the cells and / or the additives to the cell wall takes place in vitro. So z. B. in vitro, the hollow filament with a matrix of z. Autologous human stem cells or alternative cells and other additives intended to affect the desired cell differentiation or other properties in situ. The selection of additives, z. As collagen, growth or differentiation factors takes place depending on the target tissue in the body. The cells then preferably grow out of the hollow filament via the pores provided in at least the filled portion of the hollow filament once the hollow filament is provided in the form of the suture or a 2- or 3-dimensional structure in the target tissue.

In this way, an implant-controlled in situ differentiation of stem cells can take place. Both the cells and the additives can be protected in the interior of a resorbable hollow filament positioned in the body.

• a) Bereitstellen eines Hohlfilaments aus einem biodegradierbaren und/oder bioresorbierbaren Polymer mit einem durch einen Mantel und zwei offenen Enden umschlossenen Hohlraum;
• b) Besiedeln der inneren Mantelfläche und/oder eines Füllelements mit Zellen;
• c) ggf. Befüllen des Hohlraums in zumindest einem Abschnitt mit dem besiedelten Füllelement.

In addition, the invention relates to a method for producing a surgical implant, in particular a microsurgical implant, in particular of the type described above, comprising the steps:

• a) providing a hollow filament of a biodegradable and / or bioresorbable polymer having a cavity enclosed by a jacket and two open ends;
• b) colonizing the inner lateral surface and / or a filling element with cells;
• c) optionally filling the cavity in at least one section with the populated filling element.

This implant can then be inserted into the body to release cells.

It is preferably provided as a further step that additives are introduced or introduced onto the filling element and / or the inner and / or outer lateral surface of the hollow filament. These are then used to influence the cell, in particular the differentiation of stem cells to the desired cells at the site of implantation z. B. to heart, connective tissue or bone cells.

The production of the hollow films can be carried out from a polymer solution conventionally in the wet-spinning process.

An embodiment of the invention will be illustrated in the following drawings.

The single figure shows a hollow filament 10 , here only a section 12 of the hollow filament 10 is shown. The hollow filament consists of a bioresorbable polymer, in particular PLLA or PLGA and has a jacket 14 which defines essentially the cylindrical shape of the hollow filament and two open ends, wherein here the open ends of the section with 16a and 16b are designated, the open ends of the entire hollow filament 10 however, in the longitudinal direction of the hollow filament 10 can be spaced, since the hollow filament 10 a greater longitudinal extent than the section 12 can have. Alternatively, the section 12 and the hollow filament 10 however, have the same length, ie the entire hollow filament 10 forms the section 12 ,

The section of the hollow filament 12 that is shown is in its interior (cavity 15 ) filled with a filling element (not shown) in the form of a collagen matrix, wherein the filling element with stem cells 18 , in particular human autologous stem cells before introduction into the hollow filament 10 has been settled. Furthermore, differing factors are the first additive on the filling element 20 , which are present as an encapsulated differentiation factor provided.

The filling of the section presented here 12 of the hollow filament 10 , wherein the hollow filament 10 is used as a surgical implant, in particular as a microsurgical suture, done in vitro prior to the introduction of the implant into the human or animal body.

In addition, on the outer lateral surface 14 , with 14a is designated, another additive 24 , in particular modulating additive z. B. VEGF arranged.

The filled implant, on which also at least in the area of the section 12 the second additive 24 on the lateral surface 14 is attached, then by microsurgical intervention to the desired place where the stem cells 18 be released. Due to the provided additives 20 . 24 , in particular the differentiation factors 20 then can the stem cells 18 be differentiated to the desired cells.

In addition, the coat indicates 14 pore 22 on top of the cavity 15 connect with the environment that allow the exit of the differentiated stem cells, in particular a outgrowth of the cells 18 into the target tissue is made possible.

It is particularly advantageous that the implant both the stem cells 18 as well as the differentiation factors 20 as well as other additives 24 includes, where the stem cells 18 together with the differentiation factors 20 protected inside 15 of the hollow filament 10 are arranged and can be positioned at the desired location in the body.

The differentiation of stem cells 18 then takes place only in situ on site with the help of the provided differentiation factors 20 and the other additives 24 , The stem cells 18 can do so with the necessary differentiation factors 20 be brought directly to the desired location in situ and introduced specifically into the damaged tissue.

Further advantages and features emerge from the other application documents.

QUOTES INCLUDE IN THE DESCRIPTION

This list of the documents listed by the applicant has been generated automatically and is included solely for the better information of the reader. The list is not part of the German patent or utility model application. The DPMA assumes no liability for any errors or omissions.

Cited patent literature

• US 4965128 [0005]
• DE 102008019748 A1 [0006]
• DE 2521793 A1 [0007]

Claims (11)

Surgical implant comprising a hollow filament ( 10 ) of a bioresorbable and / or biodegradable polymer with a jacket ( 14 ) and two open ends ( 16a , b) and a cavity enclosed therebetween ( 15 ), characterized in that in the cavity ( 15 ) of the hollow filament ( 10 ) at least in one section ( 12 ) of the hollow filament ( 10 ) Cells ( 18 ), the cells ( 18 ) either on the inner lateral surface and / or on one in at least the section ( 12 ) provided filling element are arranged. Implant according to claim 1, characterized in that the cells ( 18 ) are autologous and / or non-autologous stem cells, in particular autologous human stem cells, or differentiated tissue cells. Implant according to claim 1 or 2, characterized in that on the filling element and / or the inner / or the outer lateral surface ( 14 . 14a ) Additives ( 20 . 24 ) are arranged to influence cell differentiation and / or cell growth. Implant according to claim 3, characterized in that the additives ( 20 . 24 ) Are growth factors or differentiation factors. Implant according to one of the preceding claims, characterized in that the filling element is a carrier matrix, in particular a collagen matrix. Implant according to one of the preceding claims, characterized in that the jacket ( 14 ) of the hollow filaments ( 10 ) at least in the section ( 12 ) Pores ( 22 ) to the passage of the cells ( 18 ) having. Implant according to one of the preceding claims, characterized in that the implant is a microsurgical suture. Implant according to one of the preceding claims, characterized in that the hollow filaments ( 10 ) are connected to 2- or 3-dimensional structures. Implant according to one of the preceding claims, characterized in that the bioresorbable and / or biodegradable polymer is selected from polylactides (PLA, PLLA), polyglycoids (PGA), glycolide / lactide copolymers (PLGA), polydiaxonones. Process for producing a surgical implant, in particular according to one of claims 1 to 9, comprising the steps of: - Providing a hollow filament with a enclosed by a sheath and two open ends cavity; - Colonization of the inner surface and / or a filling with cells; - If necessary, filling the cavity in at least one section with the populated filling. A method according to claim 10, characterized in that on the filling and / or the inner and / or outer surface additives and / or introduced.

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