WO2013083480A1

WO2013083480A1 - Joint scaffold

Info

Publication number: WO2013083480A1
Application number: PCT/EP2012/074031
Authority: WO
Inventors: Hermann Seitz; Patrick Warnke; Sebastian SPATH
Original assignee: Universität Rostock; Universitätsklinikum Schleswig-Holstein
Priority date: 2011-12-07
Filing date: 2012-11-30
Publication date: 2013-06-13
Also published as: DE102011087899A1; DE102011087899B4

Abstract

The invention relates to a resorbable, patient-specific joint replacement (joint scaffold). The aim of the invention is to provide a resorbable, patient-specific joint replacement that is biologized by means of endocultivation and optionally then transplanted into the defect region or is cultivated directly at the recipient location or in the anatomical environment. Said aim is achieved by a joint scaffold composed of a bioresorbable material, which is characterized in that two opposite halves having a concave and a convex surface directed toward each other are provided, which surfaces are spaced apart by a joint gap lying therebetween, and that the two halves each have a large central channel and interconnecting complex channel networks, the shape and the size of the joint scaffold being adapted specifically to the defect from computer tomography data of a patient, produced specifically for the patient by means of an additive production method, and biologized by means of endocultivation.

Description

Gelenkscaffold

description

The invention describes a resorbable, patient-individual

Joint replacement (joint scaffold).

State of the art

The therapy of joint defects is a difficult problem in orthopedics and accident and recovery surgery.

Caused by trauma, malformations, signs of wear and tear (arthritis), arthritis (especially rheumatism) or after tumor surgery, the use of joint prostheses is often necessary. Prostheses have been used, for example, as knee, hip or

Finger joint replacement in different design are used, which have the restoration of joint function as the goal. These consist of non-resorbable, exogenous materials, e.g. Titanium, so remain as a permanent implant in the body. These replacement joints may have ceramic and plastic components. Due to the mechanical load it comes to signs of wear on

Joint and in contact with the surrounding bone tissue, what

Follow-up operations and thus additional burden on the patient has the consequence. In particular, the limited durability of the anchoring of hip endoprostheses and the associated need for

Revision surgery is a very big problem. Permanent implants made of titanium are often felt by the patient as a permanent foreign body. Another problem is that so far only standardized replacement joints are offered on the market. This is the individual consideration of the patient in terms of

Anatomy and constitution of the skeleton in the choice of a suitable implant often insufficiently possible. In the hitherto predominantly used implants of titanium or cobalt-chromium alloys, due to the lack of porosity of the materials, previously a prior cultivation of the joints with the body's own cells has been dispensed with. Thus, an insufficient integration of the joint into the organism must be accepted. Complete joints of resorbable materials are currently not available on the market.

However, bone substitutes as well as cartilage replacement materials are known, which consist of ceramic or polymer and are completely absorbable. Thus, WO 01 17463 A1 discloses an absorbable scaffold intended to replace damaged cartilage in a joint, such as a knee joint. The scaffold includes a network of non-rigid "partitions" that effectively break a large defect into smaller bins. Each compartment has an area of typically less than 1 square centimeter. This allows chondrocyte cells to be implanted for the regeneration of cartilage. The separations can be made from a slowly resorbable material so that they are gradually absorbed until the regenerated cartilage is able to function without further assistance.

The patent application US 200819521 1 A1 includes a method for

Disc Repair and Joint Repair Scaffolds. These are created using magnetic resonance images or combined magnetic resonance and computed tomography images as a template for either an intervertebral scaffold or a cartilage-bone scaffold with fixation on the underlying bone. The disc scaffold includes an outer ring with the desired structures and a central nucleus region, either a microstructure or a

Hydrogel may contain. There are also provided fastening straps for fixation on the bone. With this method, joint functions can not be realized. Presentation of the invention

The object of the invention is to provide a resorbable,

To provide patient-individual, biologic joint replacement, which can be easily prepared and takes over the task of a natural joint after transplantation in the defect region.

The object is achieved by a Gelenkscaffold consisting of a bioresorbable material, which is characterized in that two opposite halves are provided with a concave and a convex facing each other surface, which are spaced by an intermediate joint gap, and that both Halves each have a large central channel and interconnecting complex channel networks, wherein the shape and size of the joint caffold directly from computer tomography data of a patient individually adapted to the defect, via a generative

Manufacturing processes are produced individually for each patient and biologized using endocultivation.

The concave and the convex side of the joint caffold are firmly connected during cultivation by pins which are used to activate the

Joint function to be solved.

The Gelenkscaffold consists of synthetic raw materials and is produced by means of 3D printing process. The bioresorbable material is ceramic, polymer or a composite material.

In one embodiment, the bioresorbable material consists of

Calcium phosphate, in particular hydroxyapatite, tricalcium phosphates or biphasic calcium phosphates. The composite material consists of calcium phosphates and biopolymers.

In another embodiment, the central channel biological

Structures or additional matrices and materials introduced. These may include vessels, nerves, medullary spaces, gels and / or other substances, cytokines, growth factors, hormones,

antibacterial substances or chemotherapeutic agents.

[001] In a further embodiment, a hydrogel with cartilage cells or stem cells is introduced into the joint space.

The bone and cartilage formation in the joint scaffold is through

mechanical or electromagnetic stimulation in vivo.

The advantages of the invention will become apparent to the patient from the

Combination of a novel joint scaffold and an innovative cultivation technique. The patient defect can be accurately reconstructed before treatment with the help of computed tomography data. The individually designed joint scaffold can be directly designed and manufactured with the help of the obtained dataset by means of generative manufacturing processes and thus has a high accuracy of fit. Through the use of a generative manufacturing process to make the joint caffold, e.g. 3D printing, fused deposition modeling, selective laser sintering or stereolithography also make it possible to introduce complex channel structures into the interior of the joint. Thus, it is possible to provide the joint scaffold with a complex channel system for the targeted ingrowth of hard and various soft tissues (e.g., nerves, vessels, periosteum, muscle, tendon tissue, etc.). In the middle runs a large central channel and provides the articular surfaces during cultivation optimally. The previous endocultivation allows optimal biologization of the scaffold and thus a good integration at the defect site of the patient. Furthermore, the use of resorbable material stimulates the bone remodeling process. The joint scaffold is degraded during this process and replaced by human bone. The patient will have a new, functioning, human joint at the end of treatment.

With this novel joint replacement, the view and the claim that human bone and cartilage as an ideal standard in the Reconstruction of bone and joint defects. By using endocultivation, one's own body can be used as an ideal "bioreactor" for cultivation

Manufacturing processes enable for the first time the construction of new human individualized joint structures. The success depends above all on a good integration into the organism, which is achieved by the completely new approach of endocultivation.

Embodiment of the invention

The invention will be explained in more detail with reference to drawings. 1 a, b show the joint scaffold according to the invention and FIG

FIG. 2 shows a section through the 3D jerked joint scaffold.

The joint scaffold 1 resembles in the basic form a natural joint or replacement joint and consists of a convex 4 (Figure 1a) and concave 5 (Figure 1 b) side with intervening joint gap 2. In the figure, for simplicity, the joint caffold 1 is cylindrical shown. In practice, the concrete shape of the joint is modeled on a patient-specific basis.

The joint scaffold 1 has a large central channel 3, which allows a good nutrient supply to the cells in the scaffold and in the joint space during the cultivation phase. The central channel 3 further allows manipulations in the scaffold center to different

Time points or integration of other biological structures, e.g. Vessels, nerves, medullary spaces. The central channel 3 may be provided with additional matrices and materials, e.g. Gels, to be loaded. In these can be further substances, cytokines, growth factors or

Chemotherapeutic agents are introduced to control and improve the result of cultivation. A firm connection of convex 4 and concave 5 side can be achieved during cultivation by pins 6. These pins 6 must be released for later activation of the joint function. This can be done at the place of cultivation or later during implantation at the desired location. In the joint space 2 is for example a hydrogel with cartilage cells or stem cells. The cells serve to form cartilage in joint space 2 in the course of endocultivation or in the further healing process.

The Gelenkscaffold 1 is a generative manufacturing process

Thus, it can be adapted to the defect directly on the PC using computed tomography data of the patient.

Due to the process, one is not limited in the shaping and can therefore integrate very complex channel networks 7 in the joint, which makes a previous cultivation very efficient. In order to improve the cultivation results, preliminary preliminary biologization may be performed in vitro. The actual cultivation takes place in vivo by means of the technique of endocultivation or comparable methods. In endoculture, heterotopic bone is cultured using tissue engineering techniques in vivo, for example, in the latissimus dorsi muscle or other human tissues. If the joint scaffold 1 is not cultured directly at the recipient site, it must then be transplanted into the defect region with cultured tissue.

To breed a new joint in the body of the patient becomes

individually adapted joint scaffold 1 of resorbable materials such as ceramic or polymer (e.g., calcium phosphates, in particular

Hydroxylapatite (HA), tricalcium phosphate (TCP) or biphasic

Calcium phosphate granules or biopolymers or composite materials of calcium phosphates and biopolymers) using a

produced by additive manufacturing process. By the method, complex channel networks 7 are brought into the joint caffold 1, which makes cultivation very effective. To improve the

Cultivation results may be preliminary in-vitro biologization in vitro respectively. By means of the technique of endocultivation, heterotopic bone is cultivated in vivo in humans in this scaffold. The place of cultivation does not have to match the recipient's location. Preferably endocultivation takes place in the M. latissimus dorsi of humans. The process of bone and cartilage formation as well as the

Soft tissue formation may be assisted by mechanical (for example, as disclosed in WO 20101 17275 A1) or electromagnetic stimulation in vivo. The joint caffold 1 with cultured tissue is then transplanted into the defect region. If the scaffold is cultivated immediately at the recipient site, this step is omitted. After

Implantation takes place in the course of the bone remodeling process

Deformation of the implant while simultaneously building new human bones with joint structures.

From the group of generative manufacturing processes is suitable

in particular 3D printing for the production of resorbable

Joint scaffolds 1 made of synthetic raw materials. The 3D printing process is a powder-based process for making models directly from computer data. In this process, thin layers of a powder are applied to a base plate, which is then targeted

Binder addition are solidified according to the current component cross-section. The binder is applied dropwise by means of a printhead. The building material consists of the bound powder. The loose powder takes over the support function and is removed after the end of the process. As starting materials in the 3D printing process, resorbable calcium phosphates (e.g., hydroxyapatite, tricalcium phosphate, biphasic calcium phosphates) are preferably used. These materials have already been used in plastic-reconstructive surgery to replace

Proven bone areas. These starting materials are known for their good biocompatibility and have a high osteoinductivity.

The blanks (green parts) produced in the 3D printing process are sintered in a further step at a preferred temperature of about 1250 ° C. As a result, a high final strength is achieved. In addition, will be at this step, the organic ones used in 3D printing

Binder components completely burned out.

For the preparation of patient-specific joint scaffolds 1

Used patient data obtained by computed tomography recordings. The resulting from computer tomography two-dimensional data set is using a special

Segmentation software converted into a three-dimensional surface model. After segmenting the bony structures, the data is loaded into another software tool with CAD functionality. There may e.g. By mirroring a healthy bony area on the corresponding defect area and subsequent subtraction of the two areas, the implant to be produced can be calculated. In addition, these tools are also suitable for the construction of the central channel 3 and the complex channel system 7 in the implant. Based on the three-dimensional data set, the implant can be manufactured using the 3D printing process.

The embodiment in Figure 2 shows a 3D printed

Joint scaffold 1 of hydroxyapatite. The scaffold is 67 mm long and has a diameter of 24 mm. The two joint halves are

for example, connected by four pins 6 together. In other joint forms, it may be necessary to attach two or any number of pins 6. The central channel 3 has a symmetrical

Cross section with a beam length of approx. 8 mm. The complex canal system 7 is designed for the targeted ingrowth of bone tissue and vessels as an othogonal canal network with a channel cross-section of about 0.5 mm.

The joint scaffolds 1 provide a shaping framework for

growing cells and appropriately treated surfaces will stimulate cells. Joint scaffolds 1 may be made of various resorbable materials, such as collagen-based, polylactide-based, such as biopolymers (polylactide-co-glycolide). PLGA, polycaprolactone - PCL), polyurethanes, tricalcium phosphate base and hydroxyapatite base.

In numerous fundamental investigations, the beneficial biological and technical properties of the 3D-printed scaffolds, etc. for applications in the field of endocultivation. The benefits of endocultivation have been demonstrated in several studies.

Claims

claims

1. joint scaffold, the shape and size of which is adapted to the individual patient, consists of a bioresorbable material and with the help of a

Endocultivation is biologized, characterized in that

two opposite halves are provided with a concave (5) and a convex (4) facing surface which are spaced by an intervening joint gap (2), at the time of endocultivation a firm connection between concave (5) and convex (4 ) Side, and that both halves each have a large central channel (3) and interconnecting complex channel networks (7).

2. joint scaffold according to claim 1, characterized in that

the firm connection between concave (5) and convex (4) side of the hinge caffold (1) is realized by pins (6).

3. joint scaffold according to claim 2, characterized in that

To activate the joint function, the fixed connection is released by pins (6).

4. joint scaffold according to claim 1, characterized in that

the joint scaffold (1) consists of synthetic raw materials.

5. joint scaffold according to one of claims 1 to 4, characterized in that

the bioresorbable material is ceramic, polymer or a composite material.

6. joint scaffold according to claim 5, characterized in that

the bioresorbable calcium phosphate material, in particular

Hydroxyapatite, tricalcium phosphates or biphasic calcium phosphates.

7. joint scaffold according to claim 5, characterized in that the composite material consists of calcium phosphates and biopolymers.

8. joint scaffold according to one of claims 1 to 7, characterized in that

the central channel (3) contains biological structures or additional matrices and materials.

9. joint scaffold according to claim 8, characterized in that

the central canal (3) vessels, nerves, medullary spaces, gels and / or other substances, cytokines, growth factors, hormones, antibacterial

Contains substances or chemotherapeutic agents.

10. joint scaffold according to one of claims 1 to 9, characterized in that

the joint space (2) contains a hydrogel with cartilage cells or stem cells.