Self-assembled joint hard tissue and soft tissue integrated implant and forming method

Abstract

This invention discloses a self-assembled joint implant integrating hard and soft tissue and its forming method. The implant comprises two parts: a hard tissue structure and a soft tissue structure. The hard tissue structure includes a dense hard tissue structure and a porous, loose hard tissue structure with a bidirectional gradient porosity. The soft tissue structure includes a hard soft tissue structure and a soft soft tissue structure, with different ratios of hydroxyapatite and hydrogel. The contact surfaces of the hard and soft tissue structures have corresponding serrated structures, achieving stable assembly through a combination of interference fit and friction. Furthermore, the hard tissue undergoes surface modification and is combined with a binder to promote the stability of the hydrogel applied before and after assembly, improving the firmness of the soft-hard tissue bond. The overall structure and materials of this invention exhibit continuous gradient continuity, enabling a stable transition of properties at various interfaces and reducing instability, thereby promoting post-implantation recovery and preventing loosening.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of additive manufacturing, and particularly relates to a self-assembled joint hard tissue and soft tissue integrated implant and a forming method. BACKGROUND

[0002] An artificial joint implant can replace the function of a joint, and is of great significance to the recovery of the limb function of a patient and the improvement of the quality of life. The artificial joint implant is one of the implant materials with the largest demand in orthopedics at home and abroad. With the development of medicine, people have higher and higher requirements for the performance of the artificial joint. The joint is composed of cancellous bone, compact bone and articular cartilage. In the past, the three were not distinguished in joint manufacturing, and the mechanical properties of the produced joint and the joint of the human body itself were quite different. After implantation, stress shielding effect may occur, and the patient may have problems such as bone atrophy or osteoporosis after surgery. If the joint structure is printed separately, there is currently no stable and reliable assembly method.

[0003] Most of the artificial joint implants used today are made of biologically inert metal materials or ceramics. The materials have poor bioactivity and cannot have good biocompatibility with bones. After implantation, the joint implant is prone to loosen, which makes it difficult to meet the clinical application requirements in the initial fixed position and long-term efficacy of the joint implant. SUMMARY

[0004] The main purpose of the present application is to overcome the shortcomings and deficiencies of the prior art in the preparation of artificial joints, and to provide a joint self-assembled hard tissue and soft tissue integrated implant and a forming method. By separately printing the soft tissue and hard tissue structures, the self-assembly of the two is completed through interference fit and friction, so as to achieve the purpose of simultaneous implantation of joint hard tissue and soft tissue.

[0005] In order to achieve the above purpose, the present application adopts the following technical scheme:

[0006] In one aspect of the present application, a self-assembled joint hard tissue and soft tissue integrated implant is provided, comprising a hard tissue structure and a soft tissue structure.

[0007] The hard tissue structure is printed and formed by a biocompatible metal material, the outer layer is a dense hard tissue structure, and the inside is a loose porous hard tissue structure.

[0008] The soft tissue structure is printed and formed by a biological gel material, the upper layer is a soft soft tissue structure, and the lower layer is a hard soft tissue structure.

[0009] The dense hard tissue structure of the hard tissue structure and the surface of the lower layer of the hard soft tissue structure of the soft tissue structure are respectively provided with a three-dimensional sawtooth structure, which is engaged with each other to realize integrated assembly.

[0010] Preferably, the biocompatible metal material of the hard tissue structure is pure titanium, titanium alloy or titanium-tantalum alloy.

[0011] Preferably, the surface of the hard tissue structure is subjected to modification treatment, specifically including air plasma oxidation treatment and methyl trimethoxy propyl acrylate solution immersion treatment.

[0012] Preferably, after the surface modification treatment of the hard tissue structure, the three-dimensional serrated structure of the hard tissue structure before assembly is coated with hydrogel, and the integrated implant after assembly is coated with photosensitive hydrogel and subjected to ultraviolet irradiation treatment.

[0013] Preferably, the porous hard tissue structure is a two-way gradient structure, and the overall pore size ranges from 200 to 1500 microns, and different lattice structures are used for porous design according to actual requirements; in the vertical direction, the porosity gradually decreases; in the horizontal direction, the porosity gradually increases from the outside to the inside, and the porosity of the outside gradually transitions from the dense structure to 3-30%; the porosity of the inside transitions in the range of 30-80%.

[0014] Preferably, the biogel material of the soft tissue structure is obtained by mixing hydroxyapatite, stem cells and hydrogel.

[0015] Preferably, the mass concentration of hydroxyapatite of the hard-soft tissue structure is 8%, the mass concentration of hydrogel is 20%, and the concentration of stem cells is 1.2x10 6 -1.9x10 7 mL -1 ; the mass concentration of hydroxyapatite of the soft tissue structure is 4%, the mass concentration of hydrogel is 10%, and the concentration of stem cells is 1.2x10 6 -1.9x10 7 mL -1 .

[0016] Preferably, the overall horizontal size of the serrated surface of the three-dimensional serrated structure of the hard-soft tissue structure is larger than that of the three-dimensional serrated structure of the dense hard tissue structure, so as to realize interference fit through elastic deformation of the hard-soft tissue structure.

[0017] In another aspect of the present application, a self-assembled joint hard tissue and soft tissue integrated implant forming method is provided, which is applied to the self-assembled joint hard tissue and soft tissue integrated implant, and includes the following steps:

[0018] The medical image device is used to obtain a tissue slice image of the affected part, and the slice image is imported into a medical image processing software for processing, so as to obtain a three-dimensional model of the affected part after processing;

[0019] According to the obtained three-dimensional model, forward and reverse modeling is performed to obtain a three-dimensional model of the shape and size of the hard tissue and soft tissue joint to be implanted;

[0020] The porous design and topological optimization design are performed to obtain the required bidirectional variable gradient porous structure and dense outer wall, and the bidirectional variable gradient porous structure and dense outer wall are subjected to Boolean operation with the three-dimensional model of the hard tissue to be implanted, so as to obtain a three-dimensional model of the hard tissue structure to be implanted;

[0021] Three-dimensional sawtooth structures are added to the three-dimensional models of the hard tissue structure and the soft tissue structure, respectively;

[0022] The three-dimensional models of the hard tissue structure and the soft tissue structure are imported into a slice software to generate slice files;

[0023] The soft tissue structure slice file is imported into the multi-material biological printing device host computer software, and the corresponding printing parameters of the hard-soft tissue structure and the soft-soft tissue structure are set in the host computer software. The biological gel material corresponding to the hard-soft tissue structure and the soft-soft tissue structure is added in the multi-material biological printing device, and the printing device is started to print and form the soft tissue structure;

[0024] The hard tissue structure slice file is imported into the 3D printing device, and the corresponding printing parameters are set. The printing device is started to print and form the hard tissue structure;

[0025] The printed and formed hard tissue structure is subjected to surface modification treatment, and is soaked in a connecting agent solution to make the surface of the hard tissue structure fully adhere to the connecting agent;

[0026] After the three-dimensional sawtooth structure part of the printed and formed hard tissue structure is coated with photosensitive hydrogel, the three-dimensional sawtooth structure is used for assembling the soft and hard tissue, and ultraviolet light is irradiated for curing;

[0027] The surface of the overall structure is coated with photosensitive hydrogel, and ultraviolet light is irradiated for curing to obtain the final implant.

[0028] As a preferred technical solution, the surface modification treatment of the printed and formed hard tissue structure is specifically:

[0029] The surface is subjected to air plasma treatment for oxidation;

[0030] The oxidized implant is soaked in a 2% v / v trimethoxymethyl propyl methacrylate solution, the solution temperature is 37°C, and the soaking time is 2 hours;

[0031] Rinse with ethanol and deionized water;

[0032] Dry the rinsed hard tissue structure with nitrogen.

[0033] Compared with the prior art, the present application has the following advantages and beneficial effects:

[0034] (1) The printed and shaped hard tissue structure of the present application is made of a material with superior biological properties, and adopts a bidirectional gradient porous structure, and the performance is close to that of human bone structure, which can accelerate the healing of bone tissue; the printed and shaped soft tissue structure is printed and shaped from a biological gel material mixed from hydroxyapatite, stem cells and hydrogel, and the overall performance of the hard and soft tissue structure is close to that of the subchondral bone structure, and the overall performance of the soft and soft tissue structure is close to that of the cartilage structure, realizing the bionization of the cartilage. The hard tissue structure and the soft tissue structure are both selected from materials with superior biological properties, which can promote postoperative recovery and reduce the possibility of adverse reactions after surgery.

[0035] (2) The printed and shaped hard tissue structure and the soft tissue structure of the present application are respectively provided with corresponding sawtooth structures, the sawtooth structure of the soft tissue is slightly larger than that of the hard tissue, and the soft tissue has a certain elastic deformation capacity after being printed and shaped from a biological gel material, and the purpose of self-assembly is achieved through the interference fit and the friction between the tooth surfaces, which improves the stability and reliability of the assembly, greatly simplifies the complexity of the model, and realizes the simultaneous implantation of the joint hard tissue and the soft tissue during the operation, simplifies the surgical steps and shortens the operation time.

[0036] (3) The printed and shaped hard tissue structure of the present application is surface modified to make it fully combined with the connecting agent, which can improve the adhesion of the hydrogel thereon, and further improve the stability and reliability of the combination of the soft and hard tissues.

[0037] (4) The integrated implant printed and shaped by the present application is assembled by separately printing the soft tissue and the hard tissue, and the production and processing of the two tissues can be carried out synchronously, which greatly shortens the processing time and improves the production efficiency.

[0038] (5) The dense hard tissue structure printed and shaped by the present application is a completely dense solid structure to ensure the reliability of the friction assembly and reduce the risk of loosening and falling after implantation.

[0039] (6) After the printed and shaped hard tissue structure and the soft tissue structure of the present application are assembled, the whole is coated with hydrogel, which can further strengthen the assembly effect and improve the overall biocompatibility.

[0040] (7) The printed and formed integrated implant of the present application can be topologically optimized and designed according to the different ages and implant sites of patients, and the implant is topologically optimized and designed according to the needs, different face-centered cubic, body-centered cubic structures are selected for porous filling, the matching degree of the implant is improved, and the recovery of the joint is beneficial.

[0041] (8) The hard tissue structure of the present application adopts a porous design, which has the effect of reducing weight, provides space for the growth and reproduction of bone cells, can promote the integration with the original bone after implantation, and further reduces the risk of loosening. BRIEF DESCRIPTION OF DRAWINGS

[0042] Figure 1 is a schematic diagram of the assembled joint hard tissue and soft tissue integrated implant structure of the present application;

[0043] Figure 2 is a schematic diagram of the assembled joint hard tissue and soft tissue integrated implant structure of the present application;

[0044] BRIEF DESCRIPTION OF DRAWINGS DETAILED DESCRIPTION

[0045] In order for those skilled in the art to better understand the present application, the technical solutions in the present application will be described clearly and completely below in conjunction with the drawings in the present application. Obviously, the described embodiments are only part of the embodiments of the present application, not all. Based on the embodiments in the present application, all other embodiments obtained by those skilled in the art without creative labor are within the scope of protection of the present application.

[0046] EMBODIMENT

[0047] As shown in Figure 1 , Figure 2 The present embodiment provides a self-assembled joint hard tissue and soft tissue integrated implant, comprising a hard tissue structure and a soft tissue structure.

[0048] (1) The hard tissue structure is printed and formed by biocompatible metal material, the outer layer is a completely dense solid dense hard tissue structure 3, the inside is a loose porous hard tissue structure 6, which simulates the cortical bone and cancellous bone structure of human bone; The dense hard tissue structure of the hard tissue structure is provided with a hard tissue three-dimensional sawtooth structure 5.

[0049] Further, the biocompatible metal material of the hard tissue structure is titanium alloy or PEEK.

[0050] Further, the surface of the hard tissue structure is subjected to modification treatment, specifically including air plasma oxidation treatment and methyl propyl methacrylate solution immersion treatment.

[0051] After the surface modification treatment of the hard tissue, the three-dimensional sawtooth structure 5 of the hard tissue before assembly is coated with hydrogel, and the overall integrated implant after assembly is coated with photosensitive hydrogel and subjected to ultraviolet irradiation treatment.

[0052] Further, the porous hard tissue structure 6 is a two-way gradient structure, with a pore size range of 200-1500 μm, and different lattice structures are used for porous design according to actual needs; in the vertical direction, the porosity decreases from large to small to achieve lightweight structure; in the horizontal direction, the porosity gradually increases from outside to inside, and the porosity of the outside gradually transitions from dense structure to 3-30% porosity to simulate the cortical bone structure of natural bone; the internal porosity transition range is 30-80% to simulate the cancellous bone structure of natural bone.

[0053] (2) The soft tissue structure is printed by a bio-gel material mixed from hydroxyapatite, stem cells and hydrogel, and has a soft tissue structure 4 on the upper layer and a hard soft tissue structure 1 on the lower layer; the hard soft tissue structure 1 has overall performance close to the subchondral bone structure, and the soft tissue structure 4 has overall performance close to the cartilage structure.

[0054] Further, the content of hydroxyapatite in the hard soft tissue structure 1 is higher than that in the soft tissue structure 4,

[0055] The mass concentration of hydroxyapatite in the hard soft tissue structure 1 is 8%, the mass concentration of hydrogel is 20%, and the concentration of stem cells is 1.2×10 6 -1.9×10 7 mL -1 ; the mass concentration of hydroxyapatite in the soft tissue structure 4 is 4%, the mass concentration of hydrogel is 10%, and the concentration of stem cells is 1.2×10 6 -1.9×10 7 mL -1 The proportion of hydroxyapatite in the porous structure is reduced to reduce the strength of the structure, and the deformation of the contact surface structure during assembly can be realized. The gradient change of the material composition can realize the stable transition of the cartilage tissue composition and reduce the instability of the interface.

[0056] (3) The dense hard tissue structure 3 of the hard tissue structure and the surface of the lower layer of the soft tissue structure of the soft hard tissue structure 1 are respectively provided with a three-dimensional sawtooth structure, wherein the soft tissue structure is printed with a certain elastic deformation capacity after being formed by a biological gel material, the overall horizontal size of the sawtooth surface of the soft tissue three-dimensional sawtooth structure 2 is slightly larger than the overall horizontal size of the sawtooth surface of the hard tissue three-dimensional sawtooth structure 5 (in this embodiment, the overall horizontal size of the sawtooth surface of the soft tissue three-dimensional sawtooth structure 2 is 1.1 times the overall horizontal size of the sawtooth surface of the hard tissue three-dimensional sawtooth structure 5), so as to realize interference fit of the two through elastic deformation of the soft hard tissue structure 1, achieve the effect of enhancing friction fixation, and realize integrated assembly through mutual engagement.

[0057] The integrated implant overall structure is designed according to the tissue structure of the patient's own bone injury, and the structure of the porous hard tissue is obtained through topological optimization.

[0058] In another embodiment of the present application, a self-assembled joint hard tissue and soft tissue integrated implant forming method is provided, which can be used to manufacture the self-assembled joint hard tissue and soft tissue integrated implant of the above-mentioned embodiment, and comprises the following steps:

[0059] S1, obtaining a tissue slice image of the affected area using a medical imaging device, importing the slice picture into a medical image processing software Mimics for processing, and obtaining a three-dimensional model of the affected area after processing;

[0060] S2, obtaining a three-dimensional model of the joint hard tissue and soft tissue shape size to be implanted through CAD software or UG NX software according to the obtained three-dimensional model;

[0061] S3, using CAD software to perform porous design and topological optimization design to obtain a required bidirectional variable gradient porous structure and a dense outer wall, and performing Boolean operation on the bidirectional variable gradient porous structure and the dense outer wall and the three-dimensional model of the hard tissue to be implanted to obtain a three-dimensional model of the hard tissue structure to be implanted;

[0062] S4, adding a three-dimensional sawtooth structure to the three-dimensional models of the hard tissue structure and the soft tissue structure respectively using CAD software;

[0063] S5, importing the three-dimensional models of the hard tissue structure and the soft tissue structure into a slice software respectively to generate slice files;

[0064] S6, importing the soft tissue structure slice file into the host computer software of the multi-material biological printing device, setting the corresponding printing parameters of the soft hard tissue structure 1 and the soft soft tissue structure 4 in the host computer software, adding the biological gel materials corresponding to the soft hard tissue structure 1 and the soft soft tissue structure 4 in the multi-material biological printing device, and starting the printing device to print and form the soft tissue structure;

[0065] S7. Import the hard tissue structure slice file into the metal laser 3D printing equipment, set the corresponding printing parameters, and start the printing equipment to print out the hard tissue structure.

[0066] S8. Perform surface modification treatment on the printed hard tissue structure and immerse it in the binder solution to ensure that the binder is fully adhered to its surface.

[0067] Furthermore, the surface modification treatment of the printed hard tissue structure specifically includes:

[0068] The surface is oxidized by air plasma treatment;

[0069] The oxidized implant was immersed in a 2% v / v trimethoxypropyl methacrylate (TMSPMA) solution at 37°C for 2 hours.

[0070] Rinse with ethanol and deionized water;

[0071] The rinsed hard tissue structure was dried with nitrogen gas.

[0072] S9. After coating the three-dimensional serrated structure part of the printed hard tissue structure with photosensitive hydrogel, the soft and hard tissues are assembled using the three-dimensional serrated structure, and then cured by irradiating with ultraviolet light for 30 seconds.

[0073] S10. Coat the surface of the overall structure with photosensitive hydrogel and cure it by irradiating it with an ultraviolet lamp for 30 seconds to obtain the final implant.

[0074] It should be understood that, in this specification, terms such as “comprising,” “including,” or any other variations thereof are intended to cover a non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements includes not only those elements but also other elements not expressly listed, or elements inherent to such a process, method, article, or apparatus. Without further limitation, an element defined by the phrase “comprising one…” does not exclude the presence of other identical elements in the process, method, article, or apparatus that includes said element.

[0075] The above embodiments are preferred embodiments of the present invention, but the embodiments of the present invention are not limited to the above embodiments. Any changes, modifications, substitutions, combinations, or simplifications made without departing from the spirit and principle of the present invention shall be considered equivalent substitutions and shall be included within the protection scope of the present invention.

Claims

1. A self-assembling joint hard and soft tissue integrated implant, characterized in that, This includes both hard and soft tissue structures. The hard tissue structure is formed by printing biocompatible metal materials, with a dense hard tissue portion on the outer layer and a loose and porous hard tissue portion on the inside. The loose, porous hard tissue portion exhibits a bidirectional gradient structure, with an overall pore size ranging from 200µm to 1500µm. Different lattice structures are employed for porous design based on specific requirements. Vertically, the porosity decreases; horizontally, the porosity gradually increases from the outside to the inside, with the external porosity transitioning from a dense structure to 3-30%, while the internal porosity ranges from 30-80%. The soft tissue structure is formed by printing with a biogel material, with a soft upper layer and a hard lower layer. The biogel material of the soft tissue structure is obtained by mixing hydroxyapatite, stem cells, and hydrogel. The hard soft tissue portion has a hydroxyapatite mass concentration of 8%, a hydrogel mass concentration of 20%, and a stem cell concentration of 1.2×10⁶-1.9×10⁷ mL⁻¹. The soft soft tissue portion has a hydroxyapatite mass concentration of 4%, a hydrogel mass concentration of 10%, and a stem cell concentration of 1.2×10⁶-1.9×10⁷ mL⁻¹. The dense hard tissue portion of the hard tissue structure and the hard soft tissue portion of the lower layer of the soft tissue structure each have a three-dimensional serrated structure on their surfaces, which mesh with each other to achieve integrated assembly.

2. The self-assembly joint hard and soft tissue integrated implant according to claim 1, characterized in that, The biocompatible metallic material of the hard tissue structure is pure titanium or titanium alloy.

3. The self-assembly joint hard and soft tissue integrated implant according to claim 1, characterized in that, The surface of the hard tissue structure is modified before assembly, specifically including air plasma oxidation treatment and immersion treatment in trimethoxypropyl methacrylate solution.

4. The self-assembly joint hard and soft tissue integrated implant according to claim 3, characterized in that, After surface modification of the hard tissue as a whole, hydrogel is coated on the three-dimensional serrated structure of the hard tissue structure before assembly, and the entire assembled integrated implant is coated with photosensitive hydrogel and treated with ultraviolet light.

5. The self-assembly joint hard and soft tissue integrated implant according to claim 1, characterized in that, The overall horizontal dimension of the serrated surface of the three-dimensional serrated structure of the hard soft tissue part is larger than that of the overall horizontal dimension of the serrated surface of the three-dimensional serrated structure of the dense hard tissue part, so as to achieve an interference fit between the two through the elastic deformation of the hard soft tissue part.

6. A method for forming a self-assembled joint hard and soft tissue integrated implant according to any one of claims 1-5, characterized in that, Includes the following steps: Medical imaging equipment is used to obtain tissue slice images of the affected area. The slice images are then imported into medical image processing software for processing, and a three-dimensional model of the affected area is obtained after processing. Based on the obtained 3D model, forward and reverse modeling is performed to obtain a 3D model of the shape and size of the joint hard and soft tissues to be implanted. Porous design and topology optimization design are performed to obtain the required bidirectional variable gradient porous structure and dense outer wall. Boolean operation is performed on the bidirectional variable gradient porous structure and dense outer wall with the three-dimensional model of the hard tissue to be implanted to obtain the three-dimensional model of the hard tissue structure to be implanted. Add three-dimensional serrated structures to the three-dimensional models of both hard and soft tissue structures; Import the 3D models of hard tissue structures and soft tissue structures into the slicing software to generate slice files; Import the soft tissue structure slice file into the host computer software of the multi-material bioprinting device, set the corresponding printing parameters for the hard and soft tissue parts in the host computer software, add the corresponding biogel material for the hard and soft tissue parts in the multi-material bioprinting device, and start the printing device to print out the soft tissue structure. Import the hard tissue structure slice file into the 3D printing equipment, set the corresponding printing parameters, and start the printing equipment to print out the hard tissue structure. The surface of the printed hard tissue structure is modified and then immersed in a binder solution to ensure that the binder is fully adhered to its surface. After coating the three-dimensional serrated structure of the printed hard tissue structure with photosensitive hydrogel, the soft and hard tissues are assembled using the three-dimensional serrated structure and cured by irradiation with ultraviolet light. The surface of the overall structure is coated with photosensitive hydrogel and cured by irradiation with ultraviolet light to obtain the final implant.

7. The method for forming a self-assembled joint hard and soft tissue integrated implant according to claim 6, characterized in that, The surface modification treatment of the printed hard tissue structure specifically includes: The surface is oxidized by air plasma treatment; The oxidized implant was immersed in a 2% v / v trimethoxypropyl methacrylate solution at 37°C for 2 hours. Rinse with ethanol and deionized water; The rinsed hard tissue structure was dried with nitrogen gas.

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