DE102012109266A1 - Implant for producing transplantable tissue piece in body of human or other vertebrate animal, is made of biocompatible frame, and insert which is inserted into frame - Google Patents

Abstract

The implant is made of a biocompatible frame (1), and an insert (2) which is inserted into the frame. The frame is extended between the periphery of open upper side of a framework and open underside of an underside frame. The insert includes a framework structure on which a transplantable tissue piece is formed. A securing device is provided on the underside frame for securing frame to a body tissue. Another securing device is provided on the upper side frame for securing frame to another body tissue.

Description

The present invention relates to an implant for producing a transplantable tissue piece in the body of a human or other vertebrate.

A challenge in plastic and reconstructive surgery is to replace missing bone material in the patient with suitable replacement structures. In particular, the reconstruction of major bone damage represents a significant clinical problem. However, even minor bone damage can cause difficulties, especially if they are in the area of the face and skull of a human, since these damages are not corrected by spontaneous repair mechanisms. There is therefore a need to be able to produce bone material in a suitable size and shape, which can then be transplanted to the site to be treated as a replacement for the missing bone substance.

To date, the autologous bone graft is the most common approach to bone replacement therapy. For this, bone material is often removed from the pelvic or fibular bone in human patients, adapted to the site to be corrected and transplanted there. However, there may be various complications at the donor site. This is one of the reasons why people have been looking for ways to create bone grafts without removing them from the patient's bone.

One way to achieve this, for example, is to inject into a "pocket" between the periosteum and bone hyaluronic acid, in the hope that it builds on this additional bone material that can then be used as a transplant. However, the bone material produced in this way is often not of the desired quality.

An alternative method provides that a hydroxyapatite roller is introduced into the muscle tissue of the patient, wherein the roller is a blood vessel is laid, which is to provide the newly emerging bone graft. However, this method has its limitations and so it is the object of the present invention to provide an improved compared to the prior art possibility of producing a bone graft, this possibility should in principle also be applicable to other tissue types.

This object is achieved according to the invention by an implant for producing a transplantable piece of tissue in the body of a human or other vertebrate, which is characterized in that the implant consists of a biocompatible frame and an insert insertable in this frame, wherein the frame extends along its circumference extends between the open frame top and the open frame bottom, and wherein the insert has a framework structure on which the transplantable tissue piece can form.

The implant of the present invention has the advantage that its frame can be arranged in the body of the human or in the body of the animal between two layers of tissue and thus defines a delimited space into which the skeletal structure insert can be placed. In most cases, it will be convenient for the frame to be relatively flat, meaning that its width and length are each less than its height. In many cases, therefore, it will be desirable for the frame to have a height in the range of 3 to 10 mm. The material thickness of the frame is in specific embodiments of the implant according to the invention in the range of 0.3 to 1.5 mm.

In principle, the frame can have any geometric shape. It is particularly favorable if the frame specifies an outer shape which corresponds to the outer shape which the tissue transplant to be produced therein should have for further use. If at the site to which the tissue graft to be generated is to be transplanted, for example a rather elongated piece of tissue is needed, then the frame should also expediently have a corresponding elongated shape.

In a specific embodiment of the invention, the frame may also have a complex shape which corresponds exactly to the shape which the tissue graft must have in order to be able to carry out the desired corrective action. This can be z. B. be a complex bone structure, which is required in the face and jaw area for bone replacement measures. For this purpose, the point at which the tissue transplant to be generated is to be transplanted can be optically detected, for example by MRT, and the frame can be generated on the basis of this data by CAD / CAM shaping. In this way, the exact replica of anatomical structures is possible.

However, the frame may also have a standard shape, for example with a rectangular base having a length in the range of 10 to 30 mm and a width in the range of 5 to 20 mm. In such a frame, then a blank can be generated, which in one later processing section can still be adapted to the site to be transplanted.

The skeletal structure insert of the implant according to the invention is dimensioned so that the insert can be inserted into the frame. Preferably, the insert does not protrude beyond the frame neither on the frame top nor on the underside of the frame. In a specific embodiment, the insert can be used accurately in the frame. Preferably, the insert with game fit into the frame can be used so that the insert easily inserted into the frame and can be easily removed from this again. In alternative embodiments, the insert is dimensioned to be insertable into the frame in a press fit such that the insert is held in the frame without further aids.

The frame of the implant according to the invention consists of a biocompatible material. A biocompatible material is understood here to be an implantable material, which is suitable for lingering for several months or years in the body of a human or animal, without having a negative effect on the human or the vertebrate. In particular, these are understood to mean those materials which after ISO 10993 certified as an implantable medical device. The biocompatibility of the frame can be ensured either that the frame consists of a suitably certified material or that the frame is coated with a suitably certified material so that the frame as a whole can be considered biocompatible.

The material of which the framework of the implant according to the invention is or is coated in specific embodiments of the invention is selected from biocompatible polyetheretherketone, biocompatible polyethylene terephthalate, biocompatible polypropylene, biocompatible ultra-high molecular weight polyethylene, biocompatible polyurethane, biocompatible polytetrafluoroethylene, biocompatible glass fiber, biocompatible carbon fiber , biocompatible ceramics, biocompatible titanium, biocompatible stainless steel and biocompatible alloys of these metals as well as combinations of the enumerated materials.

The biocompatible ceramics mentioned above include zirconium, leucite ceramics and feldspar ceramics.

Alternative materials from which the framework of the implant according to the invention can consist are the biocompatible polymers, which are listed below as possible materials of the skeletal structure insert.

In one embodiment of the invention, the framework structure of the insert of the implant according to the invention consists of an autologous, allogenetic or xenogenetic tissue material or of a biocompatible organic or inorganic material or combinations of said tissue materials, organic materials and / or inorganic materials.

In embodiments in which the framework structure of the insert is made of a fabric material, in specific embodiments it is selected from autologous, allogenic or xenogenetic bone, cartilage, fat or fibrous tissue. In addition, however, in principle all other tissue materials come into consideration, which are suitable as a skeletal structure insert of the implant according to the invention.

In the embodiments in which the framework structure of the insert consists of a biocompatible organic material, it is preferably selected from biopolymers or artificial polymers and combinations thereof.

For the purposes of the present invention, a biopolymer is a natural polymer synthesized in the cell of an animal, such as e.g. Polysaccharides, proteins, nucleic acids, or a synthetic polymer that consists of biogenic raw materials. For the purposes of the present invention, the synthetic biopolymer is preferably a biodegradable biopolymer.

For example, the biocompatible biopolymer may be selected from proteins, gelatin, hyaluronic acid, chitosan, collagen, silk, carboxymethylcellulose, agar, fibrin, alginate, blood derivatives, platelet-rich plasma, and combinations thereof.

In the embodiments of the implant according to the invention in which the biomaterial of the skeletal structure insert is a biocompatible artificial polymer, this is preferably selected from poly (ethylene glycol), polyurethane, polyacrylamide, poly (N-isopropylacrylamide), poly (acrylic acid) copolymer, poly (2 -vinylpyridine), polysiloxane, polyethylene, polyetheretherketone, polyesters, poly (alpha-hydroxy acid), poly (glycolic acid), poly (lactic acid), poly (l-lactic acid), poly (d-lactic acid), poly (ε-caprolactone), Poly (N-vinylcaprolactam), polydioxanone, polyglactin, polyglecaprone, poly (fumarate) and combinations thereof.

In certain embodiments, the material making up the skeletal structure of the insert is a biocompatible inorganic bone substitute material, such as e.g. Calcium phosphate, hydroxyapatite, beta-tricalcium phosphate, biphasic calcium phosphate, bone cement, coral limestone, biocompatible glass, and combinations thereof.

The frame of the implant according to the invention has an open frame bottom and an open frame top. Under the frame bottom is understood in the case of the present invention, the side of the frame, which is applied when implanting the implant in the body first on a tissue structure of the human or animal. The top, on the other hand, is that side which remains open after the frame has been applied to the first tissue structure in the body of the human or animal. In certain embodiments, the opening in the top is configured so that the insert can be inserted through this opening into the frame already mounted on the first fabric structure.

In alternative embodiments, the frame and insert are dimensioned so that the insert is also inserted from the bottom in the frame and the frame is then applied together with the already inserted insert on the first tissue structure in the body of the person or animal to be treated. In these embodiments, the top of the frame is preferably designed so that the insert can not fall out through the opening in the top.

In a specific embodiment of the present invention, a lid for partially or completely closing the opening in the frame top is provided on the top of the frame, or such a lid can be mounted on top of the frame.

In order to fix the frame of the implant according to the invention on the first body tissue on which the frame is applied, the frame in the embodiments in which such a fixation is desired, on the frame bottom on a fastening device, via which the frame on the first body tissue is attachable. In an alternative embodiment, in which the fixation of the frame to a second body tissue is desired, a fastening device is provided on the upper side of the frame, via which the frame can be fastened to the second body tissue.

Preferably, the frame underside is designed so that the frame underside comes to rest fully on the first body tissue, when the frame of the implant according to the invention is fixed on the first body tissue.

In specific embodiments fastening means are provided on both sides, namely a fastening device on the underside of the frame, via which the frame can be fastened to a first body tissue, and a fastening device on the frame top, via which the frame can be attached to a second body tissue.

In certain embodiments of the implant according to the invention, the fastening device on the frame underside and / or the fastening device on the frame top side designed so that a fastening means can be performed by this, with which the frame to the first body tissue or the second body tissue can be fastened. In preferred embodiments, the fastener that can be passed through the fastener on the frame bottom and / or on the frame top is selected from a screw, a thread, a clip, a bolt, or a rivet.

In principle, the implant can be applied to any tissue structure in the body on which the frame can be placed or on which the frame can be fastened in the manner described above. In preferred embodiments, the first body tissue to which the frame is attachable, bone tissue (substantia compacta or substantia cancellous bone), cartilaginous tissue or the meniscus, or an intervertebral disc. The second body tissue to which the frame is preferably attachable is the periosteum, the synovial membrane or the perichondrium.

In a specific embodiment, the first body tissue to which the frame bottom is attachable, the meniscus or an intervertebral disc, and the second body tissue to which the frame top is attachable, the synovial membrane.

In another specific embodiment, the first body tissue to which the frame bottom is attachable, cartilage tissue, and the second body tissue, to which the frame top is attachable, the perichondrium.

In yet another specific embodiment, the first body tissue to which the frame bottom is attachable in the body of the animal in the body of the implant is bone tissue, and the second body tissue to which the frame top is attachable, the periosteum, the synovial membrane, or the perichondrium.

Depending on which first body tissue and which second tissue the Implant is arranged, and depending on which skeletal structure insert and what possible additional components are introduced into the frame of the implant, results in the implant, a transplantable tissue material from one or more different tissue components. In certain embodiments, the transplantable tissue piece is bone tissue. Other embodiments are cartilaginous tissue. In yet another embodiment, the transplantable tissue piece is tendon tissue. Alternative embodiments are blood vessel tissue, adipose tissue, connective tissue or combinations of these tissues with each other and / or combinations with the other aforementioned tissue types.

As already mentioned in the preceding paragraph, in addition to the framework structure contained therein, the implant may also contain other constituents which are useful for the formation of the desired transplantable tissue piece. Accordingly, stem cells, osteoblasts, endothelial cells, pericytes, chondrocytes, precursor cells (CD34 +, CD133 +), platelet lysates or preparations, blood or blood preparations or combinations thereof may additionally be arranged in the context and / or in or on the insert.

Using the implant according to the invention, a tissue graft can be generated. Preferably, this tissue graft is bone, cartilage, blood vessel, tendon or fatty tissue. Certain embodiments are combinations of these fabrics. In particularly preferred embodiments, the graft additionally includes a piece of periosteum, synovial membrane or perichondrium with or without the supplying vascular pedicle containing the artery and vein. In more preferred embodiments, the graft additionally contains stem cells, osteoblasts, endothelial cells, pericytes, chondrocytes, progenitor cells (CD34 +, CD133 +), platelet lysates or preparations, blood or blood preparations or combinations thereof.

The aforementioned grafts are obtainable using the implant according to the invention, in which one applies a method in which the implant according to the invention is implanted in the body of a human or other vertebrate, wherein the frame base is applied or attached to a first body tissue and the frame top a second body tissue is applied or fixed, wherein by the frame between the first body tissue and the second body tissue, a delimited space is formed, in which the skeletal structure insert is arranged.

The first body tissue to which the frame base is attached by this method is preferably bone tissue (substantia compacta or substantia spongiosa). The second body tissue to which the frame top is attached is preferably the periosteum.

In specific embodiments, the first body tissue to which the frame bottom is attached, the meniscus or an intervertebral disc, and the second body tissue to which the frame top is attached are the synovial membrane.

In yet another embodiment of the method, the first body tissue to which the frame bottom is attached is cartilage tissue and the second body tissue to which the frame top is attached is the perichondrium.

In a very specific embodiment, the method in the delimited space between the first body tissue and the second body tissue additionally added additional components that may be selected from stem cells, from osteoblasts, endothelial cells, pericytes, chondrocytes, precursor cells (CD34 +, CD133 +), Platelet lysates or preparations, blood or blood preparations or combinations thereof.

The implant introduced into the body of the human or other vertebrate remains within the body until the tissue fragment formed therein has the size and shape suitable for its intended further use as a graft. In some embodiments, a residence time of at least 4 weeks is sufficient here. Other embodiments require at least 8 to 10 weeks. In other embodiments, the residence time is at least 12 weeks. The maximum residence time is 12 weeks in some embodiments, 16 weeks in other embodiments, and 24 weeks in other embodiments.

After expiration of the duration of the implant remains in the body of the human or other vertebrate, the resulting graft is removed from the body again. Subsequently, this graft can be re-implanted at a site of the same human or vertebrate to be treated or transplanted into another human or vertebrate animal in need of appropriate treatment.

Preferably, the graft is in connection with a piece of the first and / or second body tissue, on which the frame base or frame top in the body of the person or Animal was attached, taken from the body and transplanted in this form.

In the case of the present invention, the term "vertebrate" is understood to mean in principle all vertebrates. Preferably, these are mammals. In certain embodiments, the term "vertebrate" is understood to mean a dog, a cat, a goat, a sheep, a horse, a cattle or a pig.

Further features and combinations of features of the present invention and the associated advantages thereof can be taken from the figures attached to this description and the associated description of the figures.

Show here

1 FIG. 2: a schematic representation of the frame of a special embodiment of the implant according to the invention, FIG.

2 : a schematic representation of the use of a particular embodiment of the implant according to the invention and

3 : a schematic representation of a specific embodiment of the implant according to the invention with an insert inserted into the frame.

1 is a schematic representation of the frame 1 and a simple embodiment of the implant according to the invention, wherein the frame 1 has a rectangular base. Starting from this rectangular base, the frame extends along its circumference between the open frame top 3 and the open frame base 4 , In the embodiment of the frame shown here 1 are on the underside of the frame as a fastening device right and left material tabs 5 . 5 ' provided in which continuous recesses 6 . 6 ' are provided by each a fastening means, such as. As a screw can be performed, with which the frame on a body tissue such. B. a bone fastened.

In the illustrated embodiment are also on the frame top as a fastening device in the frame a plurality of continuous recesses 7 provided by a fastening means such. As a thread, can be performed, with which the frame is attachable to a second body tissue.

In 2 is one in the frame 1 from 1 usable insert 2 shown schematically. The schematic representation is limited to the outer circumference of the insert 2 without in any way the skeletal structure of the insert 2 display.

In 3 is shown as the use 2 out 2 in the frame 1 from 1 is used. It can be seen that the use 2 in the frame 1 can be used accurately, with a certain amount of play on all sides. The use 2 juts in height above the frame 1 not out.

For purposes of the original disclosure, it is to be understood that all such features as will become apparent to those skilled in the art from the present description, drawings, and claims, even though concretely described only in connection with certain other features, both individually and in the itself any combination with other of the features or feature groups disclosed herein are combinable, unless this has been expressly excluded or technical conditions make such combinations impossible or pointless. On the comprehensive, explicit representation of all conceivable combinations of features is omitted here only for the sake of brevity and readability of the description.

It should also be understood that it will be understood by those skilled in the art that the exemplary embodiments are merely illustrative of the possible embodiments of the present invention given as exemplary embodiments. It will therefore be readily understood by those skilled in the art that, in addition, all other embodiments having the inventive features or feature combinations recited in the claims or the description are within the scope of the invention. For the sake of brevity and readability of the description, the comprehensive, explicit representation of all conceivable embodiments is therefore omitted here.

LIST OF REFERENCE NUMBERS

1

 frame

2

 commitment

3

 Top border

4

 Frame bottom

5, 5 '

material tab

6, 6 '

recess

7

 recess

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 non-patent literature

• ISO 10993 [0012]

Claims (15)

Implant for producing a transplantable piece of tissue in the body of a human or another vertebrate, characterized in that the implant consists of a biocompatible frame ( 1 ) and an insert that can be used in this context ( 2 ), wherein the frame along its circumference between the open frame top ( 3 ) and the open frame underside ( 4 ), and wherein the insert has a framework structure on which the transplantable tissue piece can form. Implant according to claim 1, characterized in that the material from which the frame is made is chosen from biocompatible polyetheretherketone, biocompatible polyethylene terephthalate, biocompatible polypropylene, biocompatible ultra high molecular weight polyethylene, biocompatible polyurethane, biocompatible polytetrafluoroethylene, biocompatible glass fiber, biocompatible carbon fiber, biocompatible ceramics, biocompatible titanium , biocompatible stainless steel and biocompatible alloys of these metals as well as combinations of enumerated materials. Implant according to one of claims 1 and 2, characterized in that the framework structure of the insert consists of an autologous, allogenetic or xenogenetic tissue material or of a biocompatible organic or inorganic material or combinations thereof. Implant according to one of claims 1 to 3, characterized in that the framework structure of the insert consists of a tissue material which is selected from autologous, allogenetic or xenogenetic bone, cartilage, fat or fiber tissue. Implant according to one of claims 1 to 3, characterized in that the framework structure consists of a biocompatible organic material which is selected from biopolymers or artificial polymers and combinations thereof. Implant according to claim 5, characterized in that the biocompatible biopolymer is selected from proteins, gelatin, hyaluronic acid, chitosan, collagen, silk, carboxymethylcellulose, agar, fibrin, alginate, blood derivatives, thrombocyte-rich plasma and combinations thereof. Implant according to claim 5, characterized in that the biocompatible artificial polymer is selected from poly (ethylene glycol), polyurethane, polyacrylamide, poly (N-isopropylacrylamide), poly (acrylic acid) copolymer, poly (2-vinylpyridine), polysiloxane, polyethylene, Polyetheretherketone, polyesters, poly (alpha-hydroxy acid), poly (glycolic acid), poly (lactic acid), poly (l-lactic acid), poly (d-lactic acid), poly (ε-caprolactone), poly (n-vinylcaprolactam), polydioxanone, Polyglactin, polyglecaprone, poly (fumarate) and combinations thereof. An implant according to any one of claims 1 to 3, characterized in that the framework structure consists of a biocompatible inorganic bone substitute material selected from calcium phosphate, hydroxyapatite, beta-tricalcium phosphate, biphasic calcium phosphate, bone cement, coral limestone, biocompatible glass and combinations thereof. Implant according to one of claims 1 to 8, characterized in that on the frame bottom side a fastening device ( 5 . 5 ' ) is provided, via which the frame is attachable to a first body tissue, and / or on the frame top a fastening device ( 7 ) is provided, via which the frame is attachable to a second body tissue. Implant according to claim 9, characterized in that a fastening means can be guided by the fastening device on the frame underside and / or on the frame top, with which the frame on the first body tissue and / or the second body tissue can be fastened. Implant according to claim 10, characterized in that the fastening means is selected from a screw, a thread or a clip. Implant according to one of claims 9 to 11, characterized in that the first body tissue to which the frame is attachable, bone tissue, cartilage tissue or the meniscus or an intervertebral disc is. Implant according to one of claims 9 to 12, characterized in that the second body tissue to which the frame is attachable, periosteum, the synovial membrane or the perichondrium is. An implant according to any one of claims 1 to 13, characterized in that the transplantable piece of tissue is bone, cartilage, blood vessel, tendon, adipose tissue or combinations thereof. Implant according to one of claims 1 to 14, characterized in that in the frame and / or in or on the insert additionally stem cells, osteoblasts, endothelial cells, pericytes, chondrocytes, precursor cells (CD34 +, CD133 +), platelet lysates or preparations, blood or blood preparations, or combinations thereof.

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