DE102011087899A1 - Gelenkscaffold - Google Patents

Abstract

The invention describes a resorbable, patient-specific joint replacement (joint scaffold). The object of the invention is to provide a resorbable, patient-specific joint replacement which is biologized with the aid of endocultivation and optionally subsequently transplanted into the defect region or is cultured directly at the recipient site or in the anatomical environment. The object is achieved by a joint scaffold consisting of a bioresorbable material, which is characterized in that two opposing halves are provided with a concave and a convex facing each other, which are spaced by an intervening joint gap, and that both halves each one having large central channel and interconnecting complex channel networks, wherein the shape and size of the joint caffold are adapted directly from computed tomography data of a patient individually to the defect, produced via a generative manufacturing process patient-specific and biologized using a Endokultivierung.

Description

The invention describes a resorbable, patient-specific joint replacement (joint scaffold).

State of the art

The treatment of joint defects is a difficult problem in orthopedics and accident and recovery surgery dar. Caused by trauma, malformations, signs of wear (arthritis), arthritis (especially rheumatism) or after tumor surgery is often the use of joint prostheses necessary. In the past prostheses have been used, for example, as knee, hip or finger joint replacements in various designs, which have the goal of restoring joint function. 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. The mechanical stress causes signs of wear on the joint and in contact with the surrounding bone tissue, resulting in follow-up operations and thus additional stress for the patient. 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 also often perceived by the patient permanently as a foreign body. Another problem is that so far only standardized replacement joints are offered on the market. As a result, the individual consideration of the patient with regard to the anatomy and constitution of the skeleton in the choice of a suitable implant is 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 replacement as well as cartilage replacement materials are known, which consist of ceramic or polymer and are completely absorbable. So will in WO 0117463 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 2008195211 A1 includes a procedure 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 having the desired structures and a central nucleus region, which may contain either a microstructure or a hydrogel. 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, patient-specific joint replacement which is biologized with the aid of endocultivation and optionally subsequently transplanted into the defect region or is cultured directly at the recipient site or in the anatomical environment.

The object is achieved by a joint scaffold consisting of a bioresorbable material, which is characterized in that two opposing halves are provided with a concave and a convex facing each other, which are spaced by an intervening joint gap, and that both halves each one having large central channel and interconnecting complex channel networks, wherein the shape and size of the joint caffold are adapted directly from computed tomography data of a patient individually to the defect, produced via a generative manufacturing process patient-specific and biologized using a Endokultivierung.

The concave and convex sides of the joint caffold are firmly connected during cultivation by pins, which are released to activate joint function.

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

In one embodiment, the bioresorbable material is calcium phosphate, particularly hydroxyapatite, tricalcium phosphates or biphasic calcium phosphates. The composite material consists of calcium phosphates and biopolymers.

In another embodiment, biological structures or additional matrices and materials are introduced into the central channel. These may include vessels, nerves, medullary spaces, gels and / or other substances, cytokines, growth factors, hormones, antibacterial substances or chemotherapeutic agents.

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

Bone and cartilage formation in the joint scaffold is assisted by mechanical or electromagnetic stimulation in vivo.

The advantages of the invention arise for 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 to regard human bone and cartilage as the ideal standard in the reconstruction of bone and joint defects can be taken into account. By using endocultivation, one's own body can be used as an ideal "bioreactor" for cultivation. The materials used in combination with the manufacturing process allow the construction of new human individualized joint structures for the first time. 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. This shows

1a , b the joint scaffold according to the invention and

2 a section through the 3D-printed joint caffold.

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

The joint caffold 1 has a large central channel 3 , which provides a good nutrient supply to the cells in the scaffold and in the joint space during the cultivation phase. The central channel 3 furthermore permits manipulations in the scaffold center at different times or the integration of other biological structures, such as vessels, nerves, medullary spaces. The central channel 3 can be loaded with additional matrices and materials such as gels. In these, further substances, cytokines, growth factors or chemotherapeutic agents can be introduced to control and improve the result of the cultivation.

A firm connection of convex 4 and concave 5 Site may be during cultivation by pins 6 be achieved. 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 For example, there is a hydrogel with cartilage cells or stem cells. The cells serve to form cartilage in the joint space 2 in the course of endocultivation or in the further healing process.

The joint caffold 1 is produced via a generative manufacturing process and can thus directly from the computer from computed tomography data of the patient can be individually adapted to the defect. Due to the process one is not limited in the design and can therefore very complex sewer networks 7 integrate into 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. Will the joint caffold 1 not cultured directly at the recipient site, it must then be transplanted with cultivated tissue into the defect region.

To create a new joint in the patient's body, a customized joint scaffold is created 1 from resorbable materials such as ceramic or polymer (eg calcium phosphates, especially hydroxyapatite (HA), tricalcium phosphates (TCP) or biphasic calcium phosphate granules or biopolymers or calcium phosphate and biopolymer composite materials) using a generative manufacturing process. The process becomes complex channel networks 7 into the joint caffold 1 brought, which makes a cultivation very effective. In order to improve the cultivation results, preliminary preliminary biologization may be performed in vitro. 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 soft tissue formation can be achieved by mechanical (for example as in WO 2010117275 A1 disclosed) 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, as the bone remodeling process progresses, the implant is regressed while simultaneously building new human bone with joint structures.

From the group of generative manufacturing processes, 3D printing is particularly suitable for the production of resorbable joint scaffolds 1 from synthetic raw materials. The 3D printing process is a powder-based process for making models directly from computer data. Here, thin layers of a powder are applied to a base plate, which are then solidified by targeted binder addition corresponding 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 (eg hydroxylapatite, tricalcium phosphate, biphasic calcium phosphates) are preferably used. These materials have already proven themselves in plastic-reconstructive surgery for the replacement of 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, in this step, the organic binder components used in 3D printing are completely burned out.

For the production of patient-specific joint scaffolds 1 Patient data obtained by computed tomography recordings are used. The two-dimensional data set resulting from computed tomography is converted into a three-dimensional surface model with the aid of special segmentation software. After segmenting the bony structures, the data is loaded into another software tool with CAD functionality. There, for example, 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 design 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 2 shows a 3D printed joint caffold 1 from hydroxyapatite. The scaffold is 67 mm long and has a diameter of 24 mm. The two joint halves are for example by four pins 6 connected with each other. For other joint shapes, it may be necessary to have two or any number of pins 6 to install. The central channel 3 has a symmetrical cross section with a beam length of approx. 8 mm. The complex channel system 7 is for the targeted ingrowth of bone tissue and vessels is designed 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 by appropriately treated surfaces stimulation of cells is achieved. Gelenkscaffolds 1 can be made from various resorbable materials, such as collagen-based, Polylactide base, 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.

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

• WO 0117463 A1 [0003]
• US 2008195211 A1 [0004]
• WO 2010117275 A1 [0022]

Claims (11)

Joint scaffold consisting of a bioresorbable material, characterized in that two opposing halves with a concave ( 5 ) and a convex ( 4 ) facing each other by an intervening joint gap ( 2 ) and that both halves each have a large central channel ( 3 ) and interconnecting complex channel networks ( 7 ), the shape and size of the joint caffold ( 1 ) directly from computed tomography data of a patient individually adapted to the defect, manufactured by a generative manufacturing process patient-specific and biologized using an endocultivation. Joint scaffold according to claim 1, characterized in that the concave ( 5 ) and the convex ( 4 ) Side of the joint caffold ( 1 ) during cultivation by pins ( 6 ) is firmly connected. Joint scaffold according to claim 2, characterized in that to activate the joint function, the fixed connection by pins ( 6 ) is solved. Joint scaffold according to claim 1, characterized in that the joint scaffold ( 1 ) consists of synthetic raw materials and is produced by means of 3D printing. Joint scaffold according to one of claims 1 to 4, characterized in that the bioresorbable material is ceramic, polymer or a composite material. Joint scaffold according to claim 5, characterized in that the bioresorbable material consists of calcium phosphate, in particular hydroxyapatite, tricalcium phosphates or biphasic calcium phosphates. Joint scaffold according to claim 5, characterized in that the composite material consists of calcium phosphates and biopolymers. Joint scaffold according to one of claims 1 to 7, characterized in that in the central channel ( 3 ) biological structures or additional matrices and materials are introduced. Joint scaffold according to claim 8, characterized in that in the central channel ( 3 ) Vessels, nerves, medullary spaces, gels and / or other substances, cytokines, growth factors, hormones, antibacterial substances or chemotherapeutic agents are introduced. Joint scaffold according to one of claims 1 to 9, characterized in that in the joint space ( 2 ) a hydrogel with cartilage cells or stem cells is introduced. Joint scaffold according to one of claims 1 to 10, characterized in that the bone and cartilage formation in the joint scaffold ( 1 ) is supported by mechanical or electromagnetic stimulation in vivo.

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