WO2015185219A1

WO2015185219A1 - Production of a component for cultivating a joint surface implant

Info

Publication number: WO2015185219A1
Application number: PCT/EP2015/001146
Authority: WO
Inventors: Michael Jagodzinski
Original assignee: Michael Jagodzinski
Priority date: 2014-06-05
Filing date: 2015-06-05
Publication date: 2015-12-10
Also published as: DE102014008476A1

Abstract

The invention relates to a method for producing an individually adapted component for use in the cultivation of a joint surface implant, which method comprises the following steps: (a) carrying out tomographic imaging of bone tissue near the defect in the area of a defective joint surface and creating a first, virtual and three-dimensional model of the first bone tissue; (b) carrying out tomographic imaging of bone tissue located away from the defective joint surface and creating a second, virtual and three-dimensional model; (c) virtual definition of a defect area that is to be replaced in the bone tissue near the defect, on the basis of the first model; (d) if appropriate, virtual definition of a cultivation area in the bone tissue away from the defect on the basis of the second model; wherein the shape of the cultivation area corresponds at least in parts to the shape of the defect area; (e) virtual modelling of an individually adapted component on the basis of the first and/or second model and/or the defect area and/or cultivation area; and (f) actual production of the implantable component on the basis of the virtual component model obtained from step (e). The invention further relates to a method for cultivating a joint surface implant in the patient's own body. Furthermore, the invention relates to a method for implanting a joint surface implant.

Description

PREPARATION OF A COMPONENT FOR BREEDING A

JOINT SPACE IMPLANT

The invention relates to a manufacturing method for custom-made components, which are used in the cultivation of a joint surface implant. Furthermore, the invention relates to a method of cultivating a joint surface implant and a method for implanting a joint surface implant.

Accidents, tumors, infections or the introduction of implants and prostheses can lead to defects in tendons, bones and articular surfaces whose reconstruction is inadequately resolved.

The body's own tissue is available as a substitute material, but at the time of removal, defects at the donor site and, in some cases, other tissue properties (eg tendon as ligament replacement) must be accepted. In particular, the reconstruction of tissues with a multi-layered structure (eg cartilage bone or tendon bone) makes difficulties because the replication of such tissue with the available sampling materials succeeds only inadequately. As an alternative, a foreign body transplantation (so-called allograft) is available. This alternative has the disadvantages of a stronger rejection and foreign body reaction and the potential transmission of infectious diseases.

Most of the previously known methods of tissue engineering (so-called tissue engineering) have the disadvantage that the cultivation of new tissue takes place in technically demanding and cost-intensive laboratories, which results in high costs with insufficiently secured superiority over less expensive therapy methods.

Artificial, cell-free implants are described, for example, in US 2004/0127995 A1 or US 2004/0064194 A1. Such implants have been insufficient to replicate the body's own tissue. Above all, there is a lack of colonization with endogenous cells and there is the sometimes considerably delayed or limited degradation after implantation.

Bioreactors are known from US Pat. No. 6,228,117 B1, which are intended to ensure an organism-like supply of a tissue construct with nutrients, oxygen and electrolytes in order to support cell proliferation and cell differentiation. Disadvantages of these devices include the need to remove cells from the donor or recipient organism and vorzuhalten for these methods in a complex and costly manner clean room laboratories.

From US 6,348,069 B1 subcutaneous implants are known, which are cultivated within the same or another organism to achieve cell colonization and to produce a 3-dimensional tissue construct. So far, such developments are missing for the musculoskeletal area, where the tissue constructs are subject to other needs. In vitro studies have shown that mechanical stimulation for tendon and bone cells, and especially for progenitor cells, makes an important contribution to differentiation of the tissue. In this regard, the studies Jagodzinski, M., Breitbart, A., et al. (2008) "Influence of perfusion and cyclic compression on proliferation and differentiation of bone marrow stromal cells in 3-dimensional culture" J Biomech 41 (9): 1885-891; Jagodzinski, M., Drescher, M., et al. (2004) "Effects of cyclic longitudinal mechanical strain and dexamethasone on osteogenic differentiation of human bone marrow stromal cells" Eur Cell Mater 7: 35-41, discussion 41; and Jagodzinski, M., Hankemeier, S., et al. (2005) "Influence of cyclic mechanical strain and heat of human tendon fibroblasts on HSP-72" Eur J Appl Physiol: 1-8.

So far no development is known which takes these effects directly into account in the cultivation of tissue constructs in vivo.

An object of the invention is to provide a method of cultivating articular surface implants in vivo, which enables targeted mechanical stimulation of the implants.

Another object of the invention is to provide a suitable method for implanting a so-cultivated articular implant.

Finally, it is an object of the invention to provide a method to tailor components such as bone processing tools, scaffolds and culture chambers for the cultivation of a joint surface implant. Against this background, the invention relates to a method for producing a customized component for use in the cultivation of a joint surface implant, comprising the following steps:

(a) performing a tomographic imaging procedure on defect-related bone tissue in the area of a defective articular surface and creating a first, virtual and three-dimensional model of the first bone tissue;

(b) performing a tomographic imaging procedure on defect-distant bone tissue away from the defective articular surface and creating a second, virtual and three-dimensional model;

(c) virtual definition of a defect region to be replaced in defect-related bone tissue on the basis of the first model;

(d) optionally, a virtual definition of a breeding area in the defect-distant bone tissue based on the second model, wherein the shape of the breeding area corresponds at least in sections to the shape of the defect area;

(e) virtual modeling of a component customized upon presentation of the first and / or second model and / or the defect area and / or breeding area; and

(f) realizing the implantable component by presenting the virtual component model obtained from step (e). The method can be used to grow a human articular surface implant or to grow an articular surface implant. Accordingly, the defect-related and the defect-distant bone tissue may be human or animal tissue.

Within the framework of the tomographic imaging method on defect-related bone tissue in the region of a defective joint surface, defects in the first bone tissue below the defective joint surface are imaged, so that a defect region can be defined so that the area of the defective joint surface as well as the area of any underlying bone damage can be completely detected. without selecting a too large area and thus sacrificing healthy tissue. The depicted defect near bone tissue typically includes involved and uninvolved bone tissue. In particular, discrete bone tissue also includes bone tissue that is facing the defect site on the opposite side of the joint, i. lies on the bone opposite the defect. The detection of unrelated bone tissue on the opposite bone during modeling can serve to define the defect area so that the surface of the scaffold or of the implant to be cultivated is precisely modeled.

The real generation of the component by presenting the virtual model can be done, for example, by milling or cutting from a non-individually manufactured product.

Generally, the defect articular surface may be at all joints with hyaline cartilage or fibrocartilage. In an exemplary embodiment, the defective articular surface is located in the knee joint, hip joint or shoulder joint. In another exemplary embodiment, the defective joint surface lies in the intervertebral region or on the intervertebral disc. Join these joints Defects often occur and can be treated with a suitable articular implant. In one specific example, the involved bone tissue is the femur and the uninvolved bone tissue is the patella.

In one embodiment, the defect-distant bone tissue is part of a pelvic bone or a bone of the pelvic girdle. The iliac crest is particularly suitable for the contemplated breeding of articular implants in vivo in addition to mechanical stimulation.

In one embodiment, the tomographic imaging technique is computed tomography (CT) or

Magnetic Resonance Imaging (MRI). A combination of both image data records can also be used.

In one embodiment, the component is a scaffold for the articular surface implant, a trial implant, a template, a surgical tool for bone processing, or a component of an implantable breeding hood. Within the scope of the process, several or all of said components can be prepared, steps (a) to (d) being performed only once, and steps (e) and (f) separately for each of the produced components. Thus, the implementation of two imaging methods (a) and (b) in a single appointment and a bundled modeling operation (c) and (d) to model a plurality of tailored components is sufficient.

In one embodiment, the custom component is a three-dimensional scaffold for the articular surface implant. This should be identical in shape to the defect area and is therefore and under submission of the defect area modeled. Thus, a scaffold custom-made with regard to the shape and size of the defect area is modeled and created real.

The scaffold may consist of a molded hydrogel or a protein-based scaffold. It is conceivable that the scaffold is divided into at least two sections which differ with respect to the structure of the scaffold, for example the type of hydrogel. Suitable materials include collagen, fibrin, poly sugars, e.g. Chitosan or glycosaminoglycans (GAGs), e.g. Hyaluronic acid-based materials, polyesters, polylactic acid (PLA), polyglycolic acid (PGA) and polycaprolactone (PCL). Suitable methods for real production of the scaffold include nanofiber self-assembly, textile methods, SCPL (Solvent Casting & Particulate Leaching), foaming, emulsification or freeze-drying, TIPS (Thermally Induced Phase Separation), electrospinning. In particular, 3D printing of polymer particles, FDM (Fused Deposition Modeling) or LaBP (Laser Assisted BioPrinting) may be suitable in the context of the present method.

Optionally, tissue cells such as autogenous bone cells or progenitor cells are introduced into the scaffold, which later promote tissue formation at the scaffold.

If necessary, growth factors are immobilized on the scaffold, which also later promote tissue formation at the scaffold. Examples of suitable growth factors include: Fibroblast Growth Factors (FGF), Transforming Growth Factors (TGF), Platelet Derived Growth Factors (PDGF), Epidermal Growth Factors (EGF) or Insuline Like Growth Factors (IGF). The latter IGFs can play a central role, in particular in the development of cartilage tissue. Furthermore, at least one thread can be incorporated into the scaffold, which can then facilitate the suturing at the breeding site or final implantation site or a removal from the breeding site, or a general handling. In the present case, thread is not to be understood strictly in the sense of a braided fiber strand, but rather comprises thread-like or wire-shaped structures in general. Suitable threads may for example consist of resorbable or non-absorbable plastic.

In one embodiment, the tailored component is a trial implant. The trial implant has a head section which is at least partially identical in shape to the defect region. At least in sections means that at least a substantial part of the lateral surface should be identical in shape, while for example the portion of the defect region which images the articular surface need not be imaged on the trial implant. The head section is used in the application to fit the breeding site or destination before the scaffold or implant are used. In addition to the head section, the trial implant can have a handle section, which is used for easier handling. The head section is modeled prior to real production of the trial implant as part of the procedure presenting the defect area or breeding area. In one embodiment, the trial implant is made of a plastic, preferably polyamide. The production can be done for example by milling or by sintering. One possible manufacturing variant involves laser sintering, in particular in the context of a rapid prototyping method. The use of a 3D printer is conceivable.

In one embodiment, the custom component is a template. This template can promote targeted removal of bone material at the breeding site or target site. The template is coming up their actual production modeled by presenting a virtual model. Depending on whether the template is to be used at the breeding site or at the destination, the modeling will be based on the first model and the defect area, or on the second model and the breeding area. The template preferably has a support area that represents a negative mold to the surface of the bone tissue in the adjacent to the breeding site or destination area of each existing bone tissue there. The template is designed so that the physician can orient himself at the insertion of striking bony reference points, which are easily recognizable during surgery and allow reliable placement of the template. Accordingly, the virtual definition of the breeding place and destination can be selected. It has means for guiding one or more tools for bone processing, such as holes for a drill or slots for cutting tool.

In one embodiment, the custom component is a bone contouring surgical tool, such as a cutting tool. The tailor-made tool also serves for purposeful removal of bone material at the breeding or destination site. It is modeled prior to its actual production by presenting the corresponding virtual model.

In one embodiment, the tailored component is a component of an implantable breeding hood. The component is modeled by presenting the second model and / or the breeding area. The implantable breeding hood has a framework on which a screen is held. The custom-made component may in particular be the framework. The terms scaffolding and umbrella are not necessarily to be understood in the sense of a single component. The framework can be composed of several discrete parts. Similarly, the screen can be made up of several - in

put together discrete parts. The respective discrete parts may differ in their properties. The screen can be movably held on the scaffold. In another conceivable variant, the framework and screen can be combined to form a single integral component.

The screen can be made of a rigid or elastic plastic material. A preferred choice of material is PEEK, PET or a bioinert porous material such as a ceramic. The framework may consist of a preferably rigid plastic material. A preferred choice of material is also PEEK, PET or a bioinert porous material such as a ceramic. In one embodiment, means may be provided on the scaffold for attachment to the defect-removed bone tissue. Plastic materials used are preferably non-absorbable and biocompatible.

The scaffold and / or screen (or sections thereof) may either be impermeable to water or may be porous (especially open-pored) and water-permeable. The latter allows a targeted supply of the tissue construct with tissue fluid and nutrients, while no cells or the like can happen. Suitable average pore sizes are, for example, in the range of between 1 and 100 nm, preferably in the range of between 5 and 50 nm. Tissue fluid and nutrients passing through the pores promote growth and differentiation of the cells present in the scaffold or expectant implant. In one embodiment, growth factors can be immobilized on deformable and / or rigid components. Suitable growth factors have been described above in connection with the scaffold.

The possibly deformable character of the breeding hood or the movable storage of the breeding hood or of sections thereof causes that in the implanted state Covered area reversibly deformed by the action of external force and therefore the implant maturing therein can be mechanically stimulated. The framework causes the covered area to always have a certain volume and not implode. This way you can protect the maturing implant. The framework may take the form of a bridge which has individually adapted bearing surfaces in the end regions, which forms a negative mold to the surface of the defect-distant bone tissue in the region adjacent to the breeding region and which is bent up between the two end regions. The means for attachment may be arranged at the end regions. It may, for example, be one or more openings for screws.

The invention further relates to a method for cultivating a joint surface implant in the patient's own body, comprising the following steps:

(A) optionally, performing a manufacturing method according to claim 1;

(B) performing a first surgical procedure on the patient, wherein a scaffold for the articular implant is sunk in a breeding pit, which is incorporated into the defect-distant bone tissue away from the defective joint surface to be replaced by the implant;

(C) waiting for a maturity period; and

(D) performing a second surgical procedure on the patient, wherein the articular implant is removed from the breeding pit. The first step (A) is optional. In principle, the process according to steps (B) to (C) can also be carried out independently of the preparation process according to the invention using components which are not individually adapted. Nevertheless, the previous implementation of a production process according to the invention or the use of individual components prepared according to the invention is preferred.

The method can be used to grow a human articular surface implant or to grow an articular surface implant. Accordingly, the defect-related and the defect-distant bone tissue may be human or animal tissue. The patient may be a human or animal patient.

The articular surface implant may generally be one of joints with hyaline cartilage or fibrocartilage. In one embodiment, it is an implant for the knee joint, hip joint or shoulder joint. In another embodiment, it is an implant for the intervertebral area or an intervertebral disc implant. The breeding pit can be worked into the iliac crest of the patient.

The properties of the scaffold are preferably as described in connection with the production method according to the invention, regardless of whether the scaffold was actually produced individually within the scope of a production method according to the invention or not. In one embodiment, the scaffold is manufactured by a manufacturing method according to the invention.

In one embodiment, the breeding pit and the scaffold received therein are covered with a breeding hood during the first surgical procedure. The breeding hood preferably has a framework on which a screen is held. The properties of the framework and / or screen are preferably as described in connection with the production method according to the invention, regardless of whether the framework and / or screen were produced individually within the scope of a production method according to the invention manufactured a manufacturing process according to the invention.

If the production method according to step (A) is carried out, it is expedient that the shape of the breeding pit corresponds to the shape of the virtually defined breeding area. In one embodiment, incorporation of the breeding pit is done using a custom template. In one embodiment, incorporation of the breeding pit is done using a custom bone processing tool. The properties of stencil and / or tool are preferably as described in connection with the production method according to the invention.

In one embodiment, the insertion of the scaffold is preceded by a fitting of the breeding pit with the trial implant. The fitting includes inserting the head portion of the trial implant into the breeding pit to determine fit accuracy. If the accuracy of the fit is insufficient, a fine machining of the breeding pit can be carried out. This process can be repeated several times if necessary.

In one embodiment, the maturity period is 6 to 12 weeks. There is typically no further intervention between the first and second surgical procedures. During the maturing period, the hood continuously covers the breeding pit and the scaffold or the forming implant. The method according to the invention makes it possible to grow a joint surface implant with a multilayer structure (cartilage on bone) under conditions similar to those encountered at the implantation site (nutrient supply, mechanical stress). This allows tissue to ripen with a functional structure. Breeding takes place at a site that differs from the site of implantation and can be chosen independently.

The invention further relates to a method for implanting a joint surface implant, the method comprising the following steps:

(i) performing a manufacturing method according to claim 1, or growing a joint surface implant in a method according to claim 11; and

(ii) performing a third surgical procedure on the patient, with involved bone tissue removed and replaced by the implant.

The implantation process according to step (ii) is preceded by a production process according to the invention or a cultivation process according to the invention. The use of custom-made components made according to the invention is preferred.

In one embodiment, bone tissue involved in the third surgical procedure is removed within the scope of the virtually defined defect area.

In one embodiment, the removal of the involved bone tissue is accomplished using a custom template or a custom bone processing tool. In one embodiment, inserting the implant is preceded by a fitting of the target site with the trial implant. The fitting includes inserting the head portion of the trial implant into the recess at the target site to determine fit accuracy. If the accuracy of fit is insufficient, the recess can be fine-machined at the destination. This process can be repeated several times if necessary.

Further details and advantages of the invention will be explained with reference to the figures and embodiments described below. In the figures show:

FIG. 1 shows a flow chart showing the working sequence of an embodiment of a production method according to the invention

Figure 2: Illustrations of several steps taken in the context of the first operational

Intervention of an embodiment of a breeding method according to the invention are carried out;

FIG. 3 shows a schematic representation of processes during the maturation time of an embodiment of a breeding method according to the invention;

FIG. 4 shows a further schematic representation of processes during the

Maturing time of an embodiment of a breeding method according to the invention;

FIG. 5 shows a further schematic representation of processes during the

Maturing time of an embodiment of a breeding method according to the invention; FIG. 6: schematic representations of the scaffold implanted in the body together with the breeding hood according to one embodiment of a breeding method according to the invention;

FIG. 7 shows the difference between an implant grown in the context of a method according to the invention and a comparison implant; and

Figure 8: Illustrations of several steps taken in the context of the third operational

Intervention of an embodiment of an implantation method according to the invention are performed.

FIG. 1 shows a flow chart in which a possible sequence of method steps for a production method of individually adapted components for use in the cultivation of a joint surface implant, as provided according to the invention, is described.

In a first step 1, a computed tomography (CT) method for thin slice imaging (<0.5 mm isotropic voxel size) of bone tissue is performed. This imaging is done on the one hand for the hemipelvis and on the other hand for both adjacent to the damaged joint bone, the bone with the joint surface to be replaced and the opposite bone. For example, the visualized bone sections may be parts of the femur and patella on the one hand and a portion of the iliac crest on the other hand.

In a further step 2, a virtual, three-dimensional model of the imaged bone parts is created on the basis of the sectional image. It can For example, the I-Plan and Freeform programs will be used. Smoothing of the model can be done with Meshlab ^® .

In step 3, based on the previously created model, a virtual definition of a defect area on the bone with the articular surface to be replaced takes place. The defect area should include damaged or located below a damaged articular bone tissue. This area delineation can be made, for example, with l-PLAN ^® . The result is a first definition of the shape of the desired implant (corresponds to the negative of the defect area).

After the first definition of an implant or defect region, the joint-side surface of the implant or defect region is modeled in step 4. This surface should correspond to the desired surface after treatment, ie a healthy and with the opposite bone / cartilage of the joint ideally cooperating joint surface mimic. The definition is based on the virtual model of the uninvolved tissue on the opposite bone / cartilage of the joint. Optionally, a Buhl operation may be used in this modeling.

In step 5, an estimate is made as to what strength cartilage tissue should have on the articular surface of an implant to be manufactured. Furthermore, a virtual smoothing of the virtual model takes place.

In step 6, this now finished, virtual model of the implant or defect area is used in order to select a suitable site for breeding the implant on the basis of the virtual model of the iliac crest. There is a virtual modeling of a breeding area on the iliac crest. The breeding area is the virtual counterpart of an artificially recessed pit in the iliac crest, which is intended to breed an implant. The dimensions of the breeding area are chosen so that the modeled implant can be inserted into the breeding area.

In step 7, the virtual modeling of an implantable breeding hood, which is intended to cover the breeding pit during breeding of the implant and to ensure optimal conditions for growing. The harvesting hood advantageously comprises a rigid framework and a rigid or flexible umbrella. The screen may be rigidly or movably supported on the scaffold, or may form a single integral part with the scaffold. Their modeling in step 7 takes place, in particular, in that properties of the framework and / or umbrella are adapted to the individual circumstances of the breeding area, for example with regard to the size and shape, the locations for attachment means to bone or the shape of bearing surfaces.

Furthermore, in step 7, the virtual exemption of the implant takes place.

In step 8, a virtual modeling of various tools, templates and trial implants takes place. A set of such tools, templates and trial implants are designed for the treatment of the defect site in the joint and for the cultivation of the breeding site. These tools, templates and trial implants serve to make it easier for the surgeon during surgery to make a recess shaped according to the created model at the correct location of the bone. For example, the template may be a surgical template that allows for the placement of a drill in the correct direction at the correct location. Oscillating saws, hollow drills or chisels or milling can be used here. Trial implants advantageously have a head portion that has the same shape as the modeled defect area or breeding area. This is how it is done Surgeons during surgery will be able to fine-tune the shape of the area during surgery.

Under point 9, the implant is produced from a suitable material, such as a porous biomaterial or autologous material, such as bone tissue. An example of a suitable porous biomaterial is a three-dimensionally shaped hydrogel. The plastic modeled implant is fabricated using LaBP (Laser-assisted BioPrinting), maintaining the model created in Section 7.

Under point 10, the manufacture of components of the breeding hood, as well as the production of cutting tools, templates and trial implants. The production of the trial implant consisting of polyamide and the plastic template takes place by laser sintering in the context of a rapid prototyping method under provision of the model created under point 7.

Steps 1-10 correspond to a production method according to the invention. Steps 11 and 12 symbolize a possibly subsequently occurring first surgical intervention within the scope of a breeding method according to the invention and a third surgical procedure which may subsequently be performed as part of an implantation method according to the invention.

The processes which take place during the first surgical procedure within the scope of a breeding method according to the invention are illustrated in FIG.

FIG. 2 a schematically illustrates the iliac crest 20 of a patient who has a previously virtually defined breeding area. On this breeding area, a drilling template 21 produced as part of a manufacturing method according to the invention is placed. Using this drill template 21 as well optionally using custom-made tools, a recess called a breeding pit is incorporated in the breeding area. The template is then removed and the shape and dimensions of the breeding pit are fine-tuned by the surgeon using a trial implant if necessary.

Subsequently, a scaffold is sunk in the breeding pit, as shown in Figure 2b. The dimensions of the breeding pit correspond approximately to the dimensions of the scaffold 22 for the implant.

FIG. 2c shows how the breeding pit with inserted scaffold 22 was covered by a screen 23 belonging to a custom-made breeding hood. The shield 23 has previously been custom-made in the context of a manufacturing process according to the invention, and fits exactly on the corresponding point of the pelvis. This screen 23 may be, for example, a plastic layer, such as a PEEK layer. The screen may for example consist of porous material to allow nutrients and tissue fluid to pass. However, the screen 23 can also be made impermeable to water at least in sections. Optionally, cells or growth factors can be immobilized on the screen. Optionally, certain cells or growth factors may also be applied to the implant.

FIG. 2d shows how a frame 24 belonging to the breeding hood is subsequently placed on the screen 23. It is preferably made of a rigid plastic material, such as PEEK. It can be solid or porous. The framework 24 has previously been custom-made in the context of a manufacturing process according to the invention, and fits exactly on the corresponding location of the pelvis. It has dimensions that are chosen to be the desired one Area at the desired height is exactly covered. The scaffold has holes 25 at appropriate locations for anchoring to the patient's iliac crest.

Figures 3 to 6 are schematic representations of operations during the maturation period of an embodiment of a breeding method according to the invention.

A hood 100 for covering the breeding pit and the scaffold or expectant implant has a contour 101, which is composed in sections of a flexible, water-impermeable plastic film 102 and sections of a dimensionally stable, liquid-permeable membrane 103. On the basis of the dimensionally stable membrane 103, the hood 100 may be fixed to the bone tissue of the patient.

In the chamber 104 under the hood 100, a scaffold 105 of a three-dimensionally shaped hydrogel is arranged. At scaffold 105, growth factors may be immobilized. The scaffold 105 has in the exemplary embodiment shown two discrete zones 106 and 107, which differ with regard to the structure and / or composition of the hydrogel. Zone 106 is for culturing bone cells, while zone 107 is for culturing cartilage cells. Depending on the type of tissue structure desired, the same or different growth factors may be immobilized in the respective zones 106 and 107, respectively. By the reference numeral 108 cells are shown schematically, with which the device according to the invention is loaded in the context of a method according to the invention, before the loaded device is temporarily implanted in the human or animal body. The scaffold may be a scaffold 105 which has already been matched with regard to the desired shape of the implant to be cultivated and which has been obtained as part of a production method according to the invention. Alternatively it is conceivable that it is an unshaped Scaffold 105a. Reference numerals 106a, 107a and 108a denote different zones and cells of the unshaped scaffold 105a.

In FIG. 4, reference symbol 109 schematically represents tissue fluid which penetrates through the liquid-permeable porous membrane 103 into the interior of the chamber 104 and rinses the scaffold 105 in addition to the loaded autogenous cells 108. The tissue fluid 109 contains nutrients that are supplied to the cells 108 in the scaffold 105. In the pores or on the inside of the porous membrane 103, growth factors can be immobilized, which also come into contact with the scaffold 105 or the autogenous cells 108 seated thereon. Growth factors can also be immobilized on scaffold 105 itself. Furthermore, in FIG. 4, cuttings of blood vessels 110 into the tissue construct forming in the scaffold 105 can be recognized. The tissue construct can be supplied with nutrients and oxygen from these lumps 110. The seeding of blood vessels takes place from the side of the bone tissue 112 of the patient.

FIG. 5 shows a cross section through an implanted hood and scaffold 105 according to FIGS. 3 and 4, wherein the upper illustration shows the arrangement before or immediately after the implantation, and the lower illustration shows the device a certain time after implantation. The contour 101 of the hood comprises porous sections, on the inside of which growth factors 113 are immobilized. In the lower illustration, it can be seen that tissue fluid 109 penetrates through the at least partially porous hood and flows through and around the scaffold 105 or the implant that is forming.

FIG. 6 shows how the arrangement of breeding pit, scaffold and hood 100 sits below a muscle 111 on the iliac crest bone 112. Of the Muscle may exert a force F on the assembly, this force being communicated to the scaffold 105 by the flexible components 102 of the contour 101 of the hood. Thus, the forming tissue is exposed to mechanical stimuli that simulate mechanical stimuli at the later site.

FIG. 7 compares the histology of implants after six weeks of breeding. The comparison implant shown in Figure 7a was grown without mechanical influence. The implant shown in FIG. 7b was inventively bred under the influence of mechanical compression forces. The mechanical compression forces arise on the iliac crest of the patient during the normal, everyday movement and are passed on to the implant by the partially flexible construction of the breeding hood. The histological result shown shows that the regenerated tissue 30 is much thinner and more compact under mechanical influence (FIG. 7b) than without such a stimulus (FIG. 7a). The cartilage tissue 30 according to FIG. 7b is optimally adapted in its nature to the requirements at the implantation site.

The processes which take place during the third surgical procedure in the context of an implantation method according to the invention are illustrated in FIG.

FIG. 8 a schematically illustrates a femoral roll 40 of a patient, which has a previously virtually defined defect region. The illustrated femoral roll belongs to a human patient, but of course it is of course also encompassed by the invention that the methods according to the invention are performed with regard to an animal thigh roll. On this defect area, a drilling template 41 produced as part of a manufacturing method according to the invention is placed. Under use This drilling template 41 as well as possibly using custom-made tools removes defective bone tissue at the defect area.

The template is then removed and the shape and dimensions of the recess are fine-tuned by the surgeon using a trial implant 42, if desired. This is shown in FIG. 8b.

The finished recess 43 can be seen in FIG. 8c.

Subsequently, the implant 44 is sunk with the cartilaginous joint surface in the prepared recess at the destination with a plunger. The recessed implant is shown in FIG. 8d.

In summary, when applying a method according to the invention by the immediate Einsetzbereitschaft of the implant, which results from the targeted and obtained under mechanical influence cartilage layer, resulting in up to 50% less period, which is needed for healing.

In summary, it can be seen that the methods according to the invention enable a cultivation of articular surface implants in the body of the patient. There are better compared to previously known implants, the target tissue similar properties at smaller sampling defects. In addition, transplantation of the implant may occur at a later time to give the injured breeding site time to heal (e.g., after infection). The costs for the implant are reduced compared to previous methods and the effort is reduced. The implants are mechanically stronger after cultivation and more similar to the target tissue in terms of functional structure. It is also the formation of a multi-phase tissue structure possible.

Claims

claims

1. A process for the preparation of a customized component for use in the cultivation of a joint surface implant, characterized

^■ that it includes the following steps:

(b) performing a tomographic imaging procedure on defect-distant bone tissue away from the defective articular surface and creating a second, virtual and three-dimensional model; (c) virtual definition of a defect region to be replaced in defect-related bone tissue on the basis of the first model;

(f) realizing the implantable component by presenting the virtual component model obtained from step (e).

A method according to claim 1, characterized in that the defective articular surface is located at a joint with hyaline cartilage or fibrocartilage, for example in the knee joint, hip joint, shoulder joint or intervertebral region of the patient.

Method according to one of the preceding claims, characterized in that the defect-distant bone tissue is located on the iliac crest.

Method according to one of the preceding claims, characterized in that the tomographic imaging method is computed tomography (CT) or magnetic resonance tomography (MRT).

Method according to one of the preceding claims, characterized in that the component is a three-dimensional scaffold for the implant, a trial implant, a template, a surgical tool for processing bone tissue, or a component of an implantable breeding hood.

Method according to one of the preceding claims, characterized in that the component is a three-dimensional scaffold for the implant which is identical in shape to the defect region and is modeled on presentation of the defect region.

Method according to one of the preceding claims, characterized in that it is the component is a trial implant, which has a head portion which is identical in shape to a section of the defect area or breeding area, which is modeled on presentation of the defect area or the breeding area.

Method according to one of the preceding claims, characterized in that the component is a template or a surgical tool for bone processing, which is modeled by presenting the first or second model and the defect area or breeding area.

Method according to one of the preceding claims, characterized in that it is the component or a component of an implantable breeding hood, which is modeled on presentation of the second model and / or the breeding area.

10. The method according to claim 9, characterized in that the implantable breeding hood has a framework on which a screen is held, and that it is the modeled component to scaffold and / or screen.

11. A method of cultivating an articular surface implant in the patient's own body, the method comprising the steps of:

(A) optionally, performing a manufacturing method according to claim 1;

(C) waiting for a maturity period; and

(D) performing a second surgical procedure on the patient, wherein. the articular implant is removed from the breeding pit.

12. The method according to claim 11, characterized in that it is a joint surface implant for a joint with hyaline cartilage or fibrocartilage, such as the knee joint, hip joint, shoulder joint or vertebral joint of the patient, and / or that the breeding pit in the iliac crest of the patient is incorporated.

13. The method according to claim 11, characterized in that the scaffold is manufactured by a manufacturing method according to claim 1.

14. The method according to claim 11, characterized in that the breeding pit and the scaffold received therein are covered during the first surgical procedure with a breeding hood having a frame on which a screen is held, said framework and / or screen preferably by the Manufacturing process according to claim 1 are manufactured.

15. The method according to claim 11, characterized in that the shape of the breeding pit corresponds to the shape of a production area virtually defined within the scope of a manufacturing method according to claim 1 and / or that the incorporation of the breeding pit using a manufactured in the manufacturing process according to claim 1 Template or surgical tool for bone processing is done.

16. The method according to claim 11, characterized in that the insertion of the scaffold precedes a fitting of the breeding pit with a trial implant, which was manufactured in the context of a manufacturing method according to claim 1.

17. The method according to claim 11, characterized in that the maturation period is 6 to 12 weeks.

18. A method for implanting a joint surface implant, the method comprising the following steps: (i) performing a manufacturing method according to claim 1, or growing a joint surface implant in a method according to claim 11; and

19. The method according to claim 18, characterized in that the involved bone tissue in the scope in the context of a manufacturing method according to claim 1 virtually defined defect area is removed and / or that the removal using a manufactured in the manufacturing process according to claim 1 stencil or tool for bone processing.

20. The method according to claim 18, characterized in that the insertion of the implant is preceded by a fitting of the target site with a manufactured in the context of a manufacturing method according to claim 1 trial implant.