WO2019166021A1 - 一种具有仿生功能的人工关节假体 - Google Patents

一种具有仿生功能的人工关节假体 Download PDF

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WO2019166021A1
WO2019166021A1 PCT/CN2019/076810 CN2019076810W WO2019166021A1 WO 2019166021 A1 WO2019166021 A1 WO 2019166021A1 CN 2019076810 W CN2019076810 W CN 2019076810W WO 2019166021 A1 WO2019166021 A1 WO 2019166021A1
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Prior art keywords
layer
artificial joint
joint prosthesis
porous
prosthesis
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PCT/CN2019/076810
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English (en)
French (fr)
Inventor
刘铁龙
胡一为
白广建
高欣
王静
刘永刚
陈广辉
汪洋
刘戈
曹佳实
刘伟波
杨家祥
董连峰
信保全
吕凯
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上海长征医院
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Publication of WO2019166021A1 publication Critical patent/WO2019166021A1/zh

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02—Prostheses implantable into the body
    • A61F2/30—Joints
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02—Prostheses implantable into the body
    • A61F2/30—Joints
    • A61F2/30767—Special external or bone-contacting surface, e.g. coating for improving bone ingrowth
    • A61F2/30771—Special external or bone-contacting surface, e.g. coating for improving bone ingrowth applied in original prostheses, e.g. holes or grooves
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02—Prostheses implantable into the body
    • A61F2/30—Joints
    • A61F2/3094—Designing or manufacturing processes
    • A61F2/30942—Designing or manufacturing processes for designing or making customized prostheses, e.g. using templates, CT or NMR scans, finite-element analysis or CAD-CAM techniques
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
    • A61L27/38—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix containing added animal cells
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
    • A61L27/38—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix containing added animal cells
    • A61L27/3804—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix containing added animal cells characterised by specific cells or progenitors thereof, e.g. fibroblasts, connective tissue cells, kidney cells
    • A61L27/3817—Cartilage-forming cells, e.g. pre-chondrocytes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/40—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
    • A61L27/44—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix
    • A61L27/46—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix with phosphorus-containing inorganic fillers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/56—Porous materials, e.g. foams or sponges
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02—Prostheses implantable into the body
    • A61F2/30—Joints
    • A61F2/30767—Special external or bone-contacting surface, e.g. coating for improving bone ingrowth
    • A61F2/30771—Special external or bone-contacting surface, e.g. coating for improving bone ingrowth applied in original prostheses, e.g. holes or grooves
    • A61F2002/30772—Apertures or holes, e.g. of circular cross section
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02—Prostheses implantable into the body
    • A61F2/30—Joints
    • A61F2/3094—Designing or manufacturing processes
    • A61F2002/30985—Designing or manufacturing processes using three dimensional printing [3DP]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2430/00—Materials or treatment for tissue regeneration
    • A61L2430/24—Materials or treatment for tissue regeneration for joint reconstruction

Definitions

  • the invention belongs to the technical field of medical instruments and relates to an artificial joint prosthesis having a bionic function.
  • clinically applied artificial joint materials mainly include medical metal materials and medical polymer materials.
  • the joint prosthesis is made of medical metal material.
  • the development of new titanium-based metal and the improvement of surface coating treatment technology have improved the wear resistance and mechanical properties of the metal artificial joint prosthesis, and the biosafety has also been improved.
  • problems with currently commercial artificial joint prostheses such as prone to loosening, insufficient wear resistance, low fatigue strength, and poor biomechanical compatibility.
  • the bond between the existing alloy material and the bone tissue is achieved by the fibrous structure, and a good bone-bonding interface cannot always be formed.
  • the joint pad is made of medical polymer material, and UHMWPE is widely used.
  • UHMWPE's good wear resistance, low friction and self-lubricating properties make it a component of the joint liner.
  • the metal-UHMWPE gasket friction combination greatly improves the working life of the artificial joint.
  • UHMWPE is severely worn in the late stage and often produces a large amount of wear debris.
  • the wear of UHMWPE not only directly destroys joint stability, but also produces a large amount of polyethylene debris particles. The debris particles become the third-party particles of the friction interface, and the repeated cutting and scratching of the friction interface surface aggravates the wear of the UHMWPE.
  • joint activity causes a large amount of debris including polyethylene particles and bone cement particles, which will activate macrophages and foreign body giant cells in the perimembrane surrounding the prosthesis, and promote cytokines such as TNF- ⁇ . freed.
  • cytokines can activate osteoclasts and fibroblasts, causing bone resorption, osteolysis and fibrosis around the prosthesis, destroying the interfacial bonding strength of the implant-bone tissue, and causing the prosthesis to loosen.
  • the prosthesis loosens and aggravates wear, creating a vicious cycle of wear-loose-wear.
  • the present invention provides an artificial joint prosthesis having a biomimetic function.
  • Nano-hydroxyapatite/polyamide 66 is a novel biomimetic bioceramic material with excellent biosafety, biological activity and mechanical properties matching human bones.
  • nHA/PA66 has been widely used in clinical applications such as artificial vertebral bodies, interbody fusion cages and bone filling materials. A large number of experiments have proved that this bioactive material has good osseointegration ability and can be integrated with human bone tissue.
  • the prosthesis handle ie, the embedded layer
  • made of nHA/PA66 can be well combined with the human bone to realize the vascularization of the bone tissue, avoiding the micro-motion of the implant site, which is beneficial to early clinical healing.
  • the porous nHA/PA66 preparation process is mature, the porosity and pore size are controllable, and it has good biomechanical properties. Its strength and elastic modulus are similar to those of human bones, and can be applied to the repair and reconstruction of bone at the bearing site (ie, dense layer). And the stress shielding effect is weak after implantation, which is beneficial to the growth of surrounding bone tissue and reduces the incidence of bone resorption and loosening.
  • Porous nHA/PA66 as a tissue engineering scaffold for chondrocyte culture, has the advantages of good biocompatibility and controllable pore size and porosity, and can be used as an ideal synthetic scaffold material.
  • a porous scaffold with multiple growth factors such as transforming growth factor and bone morphogenetic protein can provide a good cartilage growth microenvironment, induce proliferation and differentiation of cartilage seed cells such as chondrocytes and bone marrow mesenchymal stem cells, and secrete chondrocyte extracellular matrix.
  • the realization of the articular cartilage surface can reconstruct the joint movement function, avoid the generation of wear particles, reduce the aseptic inflammation and loosening of the prosthesis, and obtain a longer service life than the metal artificial joint.
  • the present invention provides an artificial joint prosthesis having a biomimetic function, which is composed of a porous layer, a dense layer and an embedded layer.
  • the material of the porous layer, the dense layer and the embedded layer is nano hydroxyapatite/polyamide 66.
  • the porous layer has a porous structure.
  • the porous structure has a porosity of 75% or more, preferably 85% to 90%.
  • the pores of the porous structure have an inner diameter of 100 to 800 ⁇ m, preferably 200 to 350 ⁇ m; and the pores of the porous structure have an inner diameter of 200 to 300 ⁇ m on average.
  • pores of the porous structure are continuous.
  • porous layer further includes an articular cartilage surface.
  • the articular cartilage surface is formed by cultivating a layer of chondrocytes above the porous layer.
  • the porous layer has a length of 3 to 5 mm.
  • the dense layer comprises two sets of macroporous structures perpendicular to each other; the large holes have a diameter of 6-10 mm.
  • the dense layer has a length of 10 to 25 cm.
  • the embedded layer includes four holes having a diameter of 4 to 8 mm.
  • the embedded layer has a length of 10 cm.
  • the present invention provides an artificial joint prosthesis having a biomimetic function, by utilizing a specific nano-hydroxyapatite/polyamide 66 material, in combination with the special design of the porous layer, the dense layer and the embedded layer of the present invention, For example, the design of the pore structure in the porous layer and the cultivation of the chondrocyte layer on the porous structure to form the articular cartilage surface to achieve the motor function; for example, by adding a macroporous structure in the dense layer to fill the autologous bone tissue, thereby making the artificial joint false
  • the body is “growth” with the surrounding bone tissue, which can achieve good bone tissue fusion, autologous bone tissue vascularization and better support function; thus, an artificial joint prosthesis with biomimetic function is prepared, which reduces the loosening of the prosthesis.
  • the complications extend the life of the artificial joint.
  • the invention uses the 3D printing technology to prepare the artificial joint prosthesis, and the individualized implant which is "tailor-made" by the 3D printing technology is more precisely matched with the patient's bone, and the function of the affected limb is recovered more quickly, and it is often unnecessary to try repeatedly during the operation.
  • Various types of prostheses avoid aggravating local trauma and can significantly shorten the operation time.
  • FIG. 1 is a front elevational view of an artificial joint prosthesis of the present invention.
  • FIG. 2 is a perspective view of the artificial joint prosthesis of the present invention.
  • Fig. 3 shows the shape of an artificial joint actually produced.
  • the raw materials and equipment used in the specific embodiments of the present invention are known products and are obtained by purchasing commercially available products.
  • Nano-hydroxyapatite/polyamide 66 material Sichuan Guona Technology Co., Ltd.
  • Embodiment 1 Artificial joint prosthesis of the present invention
  • the artificial joint prosthesis having the biomimetic function of the present invention is composed of a porous layer, a dense layer and an embedded layer. 1 and 3, wherein FIG. 1 and FIG. 2 show the positional relationship, the proportional relationship, and the internal structure of each layer, and FIG. 3 shows the shape of the artificial joint actually produced.
  • the size of the artificial joint can be adjusted according to the specific conditions of the patient.
  • the porous layer is an articular surface contact portion designed as a porous structure, and the material used is nano hydroxyapatite/polyamide 66.
  • the porosity of the porous structure is 85% to 90%, the inner diameter of the pores is 200 to 350 ⁇ m, and the thickness of the porous layer is 3 to 5 mm.
  • a chondrocyte layer is cultured on a porous structure, and the chondrocytes are inoculated into a porous layer and cultured in a cell culture solution to form an articular cartilage surface, thereby realizing a motor function.
  • the culture method is to inoculate chondrocytes on the surface of the porous layer, allow them to grow and multiply, and form a layer of chondrocytes.
  • the dense layer is a fusion part, and the length of the dense layer is 10-25 cm, and the specific length is determined according to the extent of the tumor of the patient, and the osteotomy site is 5 cm outside the tumor.
  • Two sets of macroporous structures with a diameter of 6 mm or 8 mm perpendicular to each other are designed to fill the autologous bone tissue. After implantation in the body, good bone tissue fusion can be achieved and autologous bone tissue vascularization can be achieved. Since the bone tissue formed by the fusion of the autologous bone tissue and the prosthesis form an interlocking structure, a better supporting function than the joint prosthesis alone can be achieved.
  • the HA/PA66 used in the present invention has good osteoconductivity, can achieve biological binding with bone tissue, and is more conducive to firm bonding of bone tissue and material to achieve a supporting function.
  • the length of the embedded layer is 10cm, and the embedded layer is the supporting fixed part.
  • This part is designed for the joint shank part, which is consistent with the common joint, but 4 fixed holes with a diameter of 4 ⁇ 8mm are added for fixing the outer fixed steel plate.
  • the artificial joint prosthesis of the foregoing one is composed of a porous layer, a dense layer and an embedded layer, and the positional relationship, the proportional relationship between the different layers, and the internal structure of each layer are introduced into the 3D printing device to form a digital model;
  • the nano-hydroxyapatite/polyamide 66 powder raw material was melted layer by layer according to the imported digital model, and the artificial joint prosthesis was finally prepared by 3D printing, and the printing temperature was 275-280 °C.
  • the artificial joint prosthesis prepared by the method of the present invention is inoculated, and the cells are cultured.
  • the artificial joint prosthesis prepared by the method of the invention is taken for bone defect reconstruction.
  • the experimental results show that the cultivation of the chondrocyte layer on the porous structure of the present invention is beneficial to the realization of the motor function; the large pore structure added by the dense layer fills the autologous bone tissue, so that the artificial joint prosthesis and the surrounding bone tissue are "growth" as one body, which can be realized. Good bone tissue fusion, autologous bone tissue vascularization and better support function.
  • the present invention provides an artificial joint prosthesis having a biomimetic function, which combines the porous layer, the dense layer and the embedded layer of the present invention by utilizing a specific nano-hydroxyapatite/polyamide 66 material.
  • Special design for example, designing the pore structure in the porous layer and cultivating the layer of chondrocytes on the porous structure to form the articular cartilage surface to achieve motor function; for example, by adding a macroporous structure in the dense layer to fill the autologous bone tissue,
  • the artificial joint prosthesis is “growth” with the surrounding bone tissue, which can achieve good bone tissue fusion, autologous bone tissue vascularization and better support function; thus, an artificial joint prosthesis with biomimetic function is prepared, and the prosthesis is reduced.
  • the complications of loosening and sinking prolong the service life of the artificial joint.
  • the invention uses the 3D printing technology to prepare the artificial joint prosthesis, and the individualized implant which is "tailor-made" by the 3D printing technology is more precisely matched with the patient's bone, and the function of the affected limb is recovered more quickly, and it is often unnecessary to try repeatedly during the operation.
  • Various types of prostheses avoid aggravating local trauma and can significantly shorten the operation time.

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Abstract

一种具有仿生功能的人工关节假体，属于医疗器械技术领域，由多孔层、致密层和嵌入层组成。人工关节假体通过利用特定的纳米羟基磷灰石/聚酰胺66材料，结合多孔层、致密层和嵌入层的特殊设计，例如，多孔层中孔结构的设计并在多孔结构上面培植软骨细胞层，形成关节软骨面，从而实现运动功能；再如，通过在致密层增设大孔结构以填充自体骨组织，使得人工关节假体与周围骨组织"生长"为一体；从而制备得到了具有仿生功能的人工关节假体，降低了假体松动下沉的并发症，延长了人工关节的使用寿命。

Description

一种具有仿生功能的人工关节假体 技术领域
本发明属于医疗器械技术领域，涉及一种具有仿生功能的人工关节假体。
背景技术
随着经济的发展和人们生活水平的提高，人工关节置换已广泛地应用于临床并取得了良好的临床效果，被公认为是各类终极关节疾病的有效治疗方法。然而，随着时间的推移，由这一手术产生的假体松动下沉等并发症也日益突出，严重影响了手术的临床疗效和患者的生活质量。一旦患者出现这些不良后果，往往需要患者进行翻修手术治疗，这不仅增加了患者的手术痛苦和医疗费用，而且翻修后的临床疗效也远不如初次手术理想。
目前，临床上应用的人工关节材料主要包括医用金属材料和医用高分子材料。关节假体由医用金属材料制成，近年来新型钛基金属的研制以及表面涂层处理技术的改进，改善了金属人工关节假体的耐磨性和力学性能，生物安全性也得以提高。然而，当前已商业化的人工关节假体存在许多问题，如易发生无菌性松动、耐磨性不足、疲劳强度低以及生物力学相容性差等。首先，现有合金材料与骨组织之间的结合靠纤维组织实现，始终无法形成良好的骨结合界面。其次，合金材料的弹性模量(E＝100～200GPa)与人体骨骼的弹性模量(E＝10～40GPa)差距悬殊，因此假体植入后将不可避免地发生应力遮挡效应。应力遮挡将使得植入体周围骨应变减少，继发骨质疏松、骨质变薄、髓腔扩大，是发生假体-骨界面微动和术后骨折甚至关节脱位的根本原因。
另外，关节衬垫由医用高分子材料制成，应用较为广泛的是超高分子量聚乙烯(UHMWPE)。UHMWPE良好的耐磨性、低摩擦性及自润滑特性使其成为关节衬垫的组成成分，组成金属-UHMWPE衬垫摩擦组合极大地提高了人工关节的工作年限。然而，UHMWPE晚期磨损严重，常产生大量磨屑。UHMWPE的磨损不仅直接破坏关节稳定性，而且产生了大量聚乙烯碎屑微粒。碎屑微粒成为摩擦界面的第三方颗粒，反复切削划伤摩擦界面表面，又加重了UHMWPE的磨损。更为重要的是，关节活动造成包括聚乙烯颗粒及骨水泥微粒在内的大量碎屑产生，将活化假体周围界膜中的巨噬细胞和异物巨细胞，促使TNF-α等细胞因子的释放。研究表明，这些细胞因子能活化破骨细胞和成纤维细胞，引起假体周围骨吸收、骨溶解和纤维增生，破坏植入物-骨组织的界面结合强度，促使假体发生松动。而假体松动又加重磨损， 形成磨损-松动-磨损的恶性循环。因此亟需通过恰当的材料和巧妙的设计制备出一种具有仿生功能的人工关节假体，解决人工关节假体松动下沉的并发症，生物性固定关节假体并降低关节面的摩擦损耗，延长假体的使用寿命。
发明内容
为了解决上述问题，本发明提供了一种具有仿生功能的人工关节假体。
纳米羟基磷灰石/聚酰胺66(nHA/PA66)是新型仿生的生物陶瓷类材料，具有优良的生物安全性、生物活性和与人体骨骼匹配的力学性能。nHA/PA66现已制成人工椎体、椎间融合器和骨填充材料等广泛应用于临床。大量实验证明，这种生物活性材料具有良好的骨整合能力，能够与人体骨组织整合。nHA/PA66制成的假体柄(即嵌入层)能与人体骨良好结合，实现骨组织血管化，避免假体植入部位发生微动,有利于早期临床愈合。目前，多孔nHA/PA66制备工艺成熟，孔隙率和孔隙尺寸可控，具有良好的生物力学性能。其强度和弹性模量与人体骨骼相似，能应用于承力部位骨的修复重建(即致密层)。且植入后应力遮挡效应弱，有利于植入周围骨组织的生长，减少了骨吸收和松动的发生率。
多孔nHA/PA66(即多孔层)作为软骨细胞培养的组织工程支架，具有生物相容性良好的优点，且孔径和孔隙率可控，可作为一种理想的人工合成支架材料。复合转化生长因子和骨形态发生蛋白等多种生长因子的多孔支架能提供良好的软骨生长微环境，诱导软骨细胞、骨髓间充质干细胞等软骨种子细胞增殖、分化，分泌软骨细胞外基质，最终获得关节软骨面。关节软骨面的实现可重建关节运动功能，且避免了磨损颗粒的产生，减少无菌性炎症和假体松动，获得比金属人工关节更长的使用寿命。
本发明提供了一种具有仿生功能的人工关节假体，它是由多孔层、致密层和嵌入层组成。
进一步的，所述多孔层、致密层和嵌入层的材料为纳米羟基磷灰石/聚酰胺66。
进一步的，所述多孔层具有多孔结构。
进一步的，所述多孔结构的孔隙率为75％以上，优选为85％～90％。
进一步的，所述多孔结构的孔的内径为100～800μm，优选为200～350μm；所述多孔结构的孔的内径平均为200～300μm。
进一步的，所述多孔结构的孔是贯通的。
进一步的，所述多孔层还包括关节软骨面。
进一步的，所述关节软骨面是通过在多孔层上面培植软骨细胞层形成的。
进一步的，所述多孔层的长度为3～5mm。
进一步的，所述致密层包括有两组互相垂直的大孔结构；所述大孔的直径为6～10mm。
进一步的，所述致密层的长度为10～25cm。
进一步的，所述嵌入层包括有4个直径为4～8mm的孔。
进一步的，所述嵌入层的长度为10cm。
本发明提供了一种具有仿生功能的人工关节假体，该人工关节假体通过利用特定的纳米羟基磷灰石/聚酰胺66材料，结合本发明多孔层、致密层和嵌入层的特殊设计，例如，多孔层中孔结构的设计并在多孔结构上面培植软骨细胞层，形成关节软骨面，从而实现运动功能；再如，通过在致密层增设大孔结构以填充自体骨组织，使得人工关节假体与周围骨组织“生长”为一体，可实现良好的骨组织融合、自体骨组织血管化和更好支撑功能；从而制备得到了具有仿生功能的人工关节假体，降低了假体松动下沉的并发症，延长了人工关节的使用寿命。
同时，本发明利用3D打印技术制备人工关节假体，利用3D打印技术“量身定制”的个体化植入物与患者骨骼匹配更精准，患肢功能恢复更快，手术过程中常无需通过反复尝试各种型号的假体，避免加重局部创伤，且可明显缩短手术时间。
显然，根据本发明的上述内容，按照本领域的普通技术知识和惯用手段，在不脱离本发明上述基本技术思想前提下，还可以做出其它多种形式的修改、替换或变更。
以下通过实施例形式的具体实施方式，对本发明的上述内容再作进一步的详细说明。但不应将此理解为本发明上述主题的范围仅限于以下的实例。凡基于本发明上述内容所实现的技术均属于本发明的范围。
附图说明
图1为本发明人工关节假体的正面示意图。
图2为本发明人工关节假体的立体示意图。
图3为实际制作而成的人工关节的形状。
具体实施方式
本发明具体实施方式中使用的原料、设备均为已知产品，通过购买市售产品获得。
纳米羟基磷灰石/聚酰胺66材料：四川国纳科技有限公司。
实施例1本发明人工关节假体
一、本发明人工关节假体的结构
本发明具有仿生功能的人工关节假体是由多孔层、致密层和嵌入层组成。如图1-图3所示，其中，图1和图2表示了不同层之间的位置关系、比例关系以及各层的内部结构，图3表示实际制作而成的人工关节的形状，制成的人工关节的尺寸可以根据患者的具体情况进行调整。
1、多孔层
多孔层为关节面接触部分，设计为多孔结构，所用材料是纳米羟基磷灰石/聚酰胺66。该多孔结构的孔隙率为85％～90％，孔的内径为200～350μm，多孔层的厚度为3～5mm
本发明通过在多孔结构上面培植软骨细胞层，将软骨细胞接种到多孔层，置于细胞培养液中培养，即可，形成关节软骨面，从而实现运动功能。培养方法是将软骨细胞接种在多孔层表面，让其生长繁殖，并形成软骨细胞层。
2、致密层
致密层为融合部分，致密层长度为10～25cm，具体长度根据病人肿瘤累及范围而定，截骨部位为肿瘤外5cm。设计两组互相垂直的直径为6mm或者8mm的大孔结构，用于填充自体骨组织，植入体内后，可实现良好的骨组织融合并能实现自体骨组织血管化。由于自体骨组织融合后形成的骨组织与假体形成了相互交锁的结构，因此可实现比单独的关节假体更好支撑功能。特别地，本发明所用HA/PA66具有良好的骨传导性，可以与骨组织实现生物性结合，更有利于骨组织与材料的牢固结合，实现支撑功能。
3、嵌入层
嵌入层长度为10cm，嵌入层为支撑固定部分，此部分为关节柄部分设计，与通用关节一致，但增设直径为4～8mm的固定孔4个，用于外固定钢板固定。
二、本发明人工关节假体的制备
(1)数据导入
将前述一中关于人工关节假体是由多孔层、致密层和嵌入层组成，且不同层之间的位置关系、比例关系以及各层的内部结构导入3D打印设备，形成数字模型；根据患者薄层CT扫描数据、MRI影像数据，确定人工关节的尺寸；
依据植骨要求设计出人工关节假体。
(2)3D打印人工关节假体
根据导入的数字模型逐层熔融纳米羟基磷灰石/聚酰胺66粉末原料，最终利用3D打印制备出人工关节假体，打印温度为275～280℃。
以下通过药效学实验说明本发明的有益效果。
实验例1多孔层不同孔径尺寸培植软骨细胞层
取本发明方法制备的人工关节假体，接种细胞，进行培养。
实验结果表明，本发明多孔层的多孔结构中特定的孔隙率和内径尺寸有利于培植软骨细胞层。
实验例2人工关节假体在大段骨缺损重建中的应用
取本发明方法制备的人工关节假体，进行骨缺损重建。
实验结果表明，本发明多孔结构上面培植软骨细胞层有利于运动功能的实现；致密层增设的大孔结构通过填充自体骨组织，使得人工关节假体与周围骨组织“生长”为一体，可实现良好的骨组织融合、自体骨组织血管化和更好支撑功能。
综上，本发明提供了一种具有仿生功能的人工关节假体，该人工关节假体通过利用特定的纳米羟基磷灰石/聚酰胺66材料，结合本发明多孔层、致密层和嵌入层的特殊设计，例如，多孔层中孔结构的设计并在多孔结构上面培植软骨细胞层，形成关节软骨面，从而实现运动功能；再如，通过在致密层增设大孔结构以填充自体骨组织，使得人工关节假体与周围骨组织“生长”为一体，可实现良好的骨组织融合、自体骨组织血管化和更好支撑功能；从而制备得到了具有仿生功能的人工关节假体，降低了假体松动下沉的并发症，延长了人工关节的使用寿命。
同时，本发明利用3D打印技术制备人工关节假体，利用3D打印技术“量身定制”的个体化植入物与患者骨骼匹配更精准，患肢功能恢复更快，手术过程中常无需通过反复尝试各种型号的假体，避免加重局部创伤，且可明显缩短手术时间。

Claims (10)

  1. 一种具有仿生功能的人工关节假体，其特征在于：它是由多孔层、致密层和嵌入层组成。
  2. 根据权利要求1所述的人工关节假体，其特征在于：所述多孔层、致密层和嵌入层的材料为纳米羟基磷灰石/聚酰胺66。
  3. 根据权利要求1所述的人工关节假体，其特征在于：所述多孔层具有多孔结构；优选地，所述多孔结构的孔隙率为75％以上，优选为85％～90％。
  4. 根据权利要求3所述的人工关节假体，其特征在于：所述多孔结构的孔的内径为100～800μm，优选为200～350μm；所述多孔结构的孔的内径平均为200～300μm。
  5. 根据权利要求3所述的人工关节假体，其特征在于：所述多孔结构的孔是贯通的。
  6. 根据权利要求1所述的人工关节假体，其特征在于：所述多孔层还包括关节软骨面；优选地，所述关节软骨面是通过在多孔层上面培植软骨细胞层形成的。
  7. 根据权利要求1所述的人工关节假体，其特征在于：所述多孔层的长度为3～5mm。
  8. 根据权利要求1所述的人工关节假体，其特征在于：所述致密层包括有两组互相垂直的大孔结构；所述大孔的直径为6～10mm；优选地，所述致密层的长度为10～25cm。
  9. 根据权利要求1所述的人工关节假体，其特征在于：所述嵌入层包括有4个直径为4～8mm的孔。
  10. 根据权利要求1所述的制备方法，其特征在于：所述嵌入层的长度为10cm。
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