Engineering construction composite artificial bone and manufacturing method thereof

Abstract

The invention discloses an engineering construction composite artificial bone based on architectural engineering and a manufacturing method thereof.The engineering construction composite artificial bone comprises a bioactive material and a mechanical supporting scaffold, the bioactive material serves as a main body, the mechanical supporting scaffold is contained in the bioactive material, and the bioactive material and the mechanical supporting scaffold are tightly combined to form an artificial bone tissue complex; the mechanical support bracket can provide mechanical support for the artificial bone tissue complex so as to meet the load requirement in the bone repair process. The artificial bone tissue complex can further achieve one or more functions through surface modification and / or a carrying structure used for carrying a bone growth promoting material release system and / or a drug release system arranged in the artificial bone tissue complex so as to meet the clinical requirements of anti-inflammation, anti-infection, anti-tumor, anti-osteoporosis, bone integration promotion and the like. The bone integration performance and mechanical performance of the material are considered, and a new scheme is provided for large-area bone defect repair, bone structure filling and supporting and parts needing long-term load bearing.

Description

Technical Field

[0001] The invention belongs to the field of biomedical engineering, and in particular relates to an engineering structured composite artificial bone and a manufacturing method thereof. Background Art

[0002] As the treatment of bone defects has attracted more and more attention, especially in the weight-bearing parts of the spine and limbs, some bone repair materials or support structures are usually used for integrated repair, but both have some shortcomings, as follows:

[0003] As for bone repair materials, the bone repair materials with strong bone integration ability are mainly calcium matrix, silicon matrix materials, polymers, and magnesium metal. They have certain bone integration ability, but the mechanical properties are not satisfactory and cannot meet the mechanical requirements of the load-bearing area. For example, calcium matrix materials have low tensile strength and bending strength, are prone to brittle fracture, and are difficult to withstand complex loads. Calcium-based materials are prone to fatigue failure, especially when used in high-intensity load-bearing areas. Silicon matrix materials have weak mechanical properties, usually low compressive strength and toughness, and are difficult to withstand long-term mechanical loads in high-load-bearing areas. They are also highly brittle and prone to crack expansion and fracture under impact or fatigue loads. Polymer materials have low mechanical strength and are difficult to meet the requirements of high compressive strength and bending resistance for bone replacement in load-bearing areas. Polymers may creep under continuous load, resulting in changes in implant morphology and functional failure. Polymer materials may degrade, fracture, and even lose mechanical properties in the body, especially under load-bearing environments. Magnesium metal has certain bone induction properties, but its degradation is uncontrollable and toxic, so it cannot be used alone. Currently, it can only be used in surface modification of materials and release through sustained-release systems.

[0004] However, polymer + calcium matrix / silicon matrix composite materials have the following problems: 1. The contradiction between mechanical properties and biological properties: the composite materials need to meet both high mechanical strength and excellent biological activity, but it is difficult to achieve an ideal balance between the two. 2. Insufficient interface bonding strength: the interface bonding between the polymer and the calcium matrix or silicon matrix is ​​often poor, which may cause the composite material to delaminate, peel or fail. Other bone integration composite materials mainly improve bone integration ability and anti-inflammatory, anti-infection, anti-tumor and other functions, but it is still difficult to meet the bone replacement repair in the load-bearing area.

[0005] For supporting structures, microporous titanium alloy materials with good mechanical properties and good biocompatibility are the most widely used materials, but they have the following disadvantages: 1. The bonding force between titanium alloy and bone is poor, the bone integration ability is insufficient, and the prosthesis is prone to loosening; 2. The elastic modulus of pure titanium alloy is large, and the bone collapse and sinking of titanium alloy at the interface are prone to occur; 3. Although the microporous structure can undergo a certain degree of bone integration, the bone integration ability is weak and can only be limited to the range of 1-3 mm at the interface. It cannot be deeply integrated and has poor mechanical properties at the interface. The above materials also do not have anti-infection and anti-inflammatory capabilities. Composite materials combined with titanium alloys are currently limited to surface modification.

[0006] In summary, there is currently a lack of artificial bones that can have good bone integration, meet the mechanical load of the weight-bearing area and have diverse bioactive functions, which cannot meet the diverse clinical needs. Therefore, there is an urgent need for a new type of engineered composite artificial bone material that combines architectural engineering. Summary of the invention

[0007] The purpose of the present invention is to provide an engineered composite artificial bone and a method for making the same, which can take into account both the bone integration performance and the mechanical properties of the material.

[0008] The present invention is achieved in this way: an engineered composite artificial bone includes a bioactive material and a mechanical support scaffold; the bioactive material serves as the main body, and contains a mechanical support scaffold inside which are tightly combined with each other to form an engineered integrated artificial bone tissue complex; the mechanical support scaffold is used to provide mechanical support for the integrated artificial bone tissue complex to meet the load requirements during bone repair.

[0009] The present invention also provides a method for preparing the above-mentioned engineered composite artificial bone, comprising the following steps:

[0010] preparing a mechanical support scaffold;

[0011] Performing surface treatment on the mechanical support bracket;

[0012] The mechanical support scaffold is combined with the bioactive material through high temperature sintering or 3D printing or plasma spraying or filling and curing to form an integrated artificial bone tissue complex;

[0013] Making a mounting structure on the surface and / or inside of the integrated bone tissue complex;

[0014] A sustained-release system containing bone growth promoting materials and / or drugs with corresponding functions is embedded into the carrying structure.

[0015] Compared with the prior art, the present invention has the following beneficial effects:

[0016] 1. The engineered composite artificial bone provided by the present invention has a built-in mechanical support scaffold that can provide sufficient mechanical support and toughness to meet the load requirements during bone repair, and provide a new treatment solution for large-area bone defect repair, bone structure filling support, and areas that require long-term load-bearing.

[0017] 2. Mechanical support The scaffold is tightly wrapped in bioactive materials, which can enhance the integration with bone tissue. The bone integration effect reaches the optimal state through the natural biological reaction with bone tissue. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] Figure 1 It is a schematic diagram of the three-dimensional structure of an engineered composite artificial bone provided by an embodiment of the present invention;

[0019] Figure 2 is a schematic top view of an engineered composite artificial bone provided by an embodiment of the present invention;

[0020] Figure 3 is a side view schematic diagram of an engineered composite artificial bone provided by an embodiment of the present invention;

[0021] Figure 4 A schematic cross-sectional view of an engineered composite artificial bone provided by an embodiment of the present invention.

[0022] Figure 5A-5H Schematic diagrams of several shapes of mechanical support brackets provided in embodiments of the present invention;

[0023] Figure 6 is a cross-sectional schematic diagram of a grid-shaped mechanical support bracket provided by an embodiment of the present invention;

[0024] Fig. 7A Schematic diagram of the application of the engineered composite artificial bone provided by an embodiment of the present invention between two spinal bones;

[0025] Figure 7B It is a schematic diagram of the application of the engineered composite artificial bone provided by an embodiment of the present invention in lower limb bone defects.

[0026] Numbers in the figure: 1-bioactive material; 2-mechanical support scaffold; 21-inner hole; 3-artificial bone tissue complex; 31-carrying structure; 32-channel; 33-micropore; 4-drug sustained-release ball. DETAILED DESCRIPTION

[0027] In order to make the purpose, technical solution and advantages of the present invention more clearly understood, the present invention is further described in detail below in conjunction with the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not intended to limit the present invention.

[0028] This embodiment provides an engineered composite artificial bone. Figures 1 to 4 The structure of the engineered composite artificial bone is shown. The engineered composite artificial bone includes a bioactive material 1 and a mechanical support scaffold 2. The bioactive material 1 is the main body, and the internal part thereof contains the mechanical support scaffold 2 and is tightly combined with the mechanical support scaffold 2 to form an engineered integrated artificial bone tissue complex 3. Specifically, the bioactive material 1 may be filled in the mechanical support scaffold 2, or the bioactive material 1 may be filled in the internal part of the mechanical support scaffold 2 and covered on the surface of the mechanical support scaffold 2. Among them, the bioactive material 1 can provide good bone integration ability, and the bone integration effect reaches the optimal state through the natural biological reaction with the bone tissue, and the mechanical support scaffold 2 can provide mechanical support and toughness for the integrated artificial bone tissue complex 3 to meet the load requirements in the bone repair process, and provide a new treatment plan for large-area bone defect repair, bone structure filling support, and parts that require long-term load-bearing.

[0029] The close combination between the bioactive material 1 and the mechanical support scaffold 2 is similar to the "rebar + cement" structure in construction engineering, which can be achieved through high-temperature sintering, 3D printing, plasma spraying or filling.

[0030] Specifically, the bioactive material 1 can be bioceramic composite particles or porous bioglass; wherein the material of the bioceramic composite particles is one or a combination of two or more of calcium hydroxide, calcium phosphate or nano-silicon dioxide. The mechanical support bracket 2 is made of one or more materials including but not limited to tantalum alloy, magnesium alloy, polylactic acid (PLA) and its copolymers, ceramics and their composites, polymers, carbon fibers and their composites.

[0031] The specific shape of the mechanical support bracket 2 is not limited, and can be designed through mechanical calculation to be any shape or style that can provide sufficient mechanical support for the entire composite artificial bone. For example, it can be Figure 5A The fence shown is Figure 5B The honeycomb shape shown, Figure 5C , Figure 5D The bifurcation pattern shown, Figure 5E , Fig. 5F , Figure 5G The grid is shown. Figure 5H The tree branches shown are like that, etc.

[0032] Furthermore, the surface and / or interior of the integrated artificial bone tissue complex 3 may be equipped with a bone growth promoting material release system and / or a drug release system. As an implementation method, a carrying structure 31 may be designed on the surface and / or interior of the integrated artificial bone tissue complex 3 to accommodate the bone growth promoting material release system and / or the drug release system. As another implementation method, the bone growth promoting material release system and / or the drug release system may also be coated on the surface of the carrying structure 31. The bone growth promoting material and / or drug in the sustained-release system is continuously and slowly released, and the drug therein may be selected according to the specific condition of the patient, and has different functions in different application scenarios.

[0033] Preferably, the bone growth promoting material is a porous calcium phosphate-based material, a silicon-based biomaterial, a polymer, a collagen and protein-based material, chitosan, a carbon-based material, a nanocomposite polymer composite material; wherein the silicon-based biomaterial may include bioglass.

[0034] Structurally, the above-mentioned bone growth promoting material release system and / or drug release system includes but is not limited to at least one of the coating on the outer surface of the integrated artificial bone tissue complex 3 and the microsphere and microcapsule release system located in the carrying structure 31.

[0035] like Figures 1 to 3 As shown, the above-mentioned microspheres can be drug sustained-release spheres 4, and the drug sustained-release spheres 4 have a coating layer and a core, and the coating layer covers the core. Among them, the coating layer is a material that can be absorbed by the human body, and can be one or more of ceramic and glass materials, biodegradable polymers, natural polymer materials, chitosan, nanomaterials, hydrogel materials, and ceramic-polymer composite materials. The core is one or more of bone growth-promoting materials, drugs, magnesium alloys, zinc alloys, and hydrogels. Through this structural design, the drug sustained-release spheres 4 can slowly release bone growth-promoting materials and / or drugs, and accelerate bone healing and repair.

[0036] Furthermore, the release rate of the bone growth promoting material and / or drug in the sustained-release system is designed in a gradient, wherein the release rate of the bone growth promoting material and / or drug near the bone contact end is greater than the release rate of the bone growth promoting material and / or drug far from the bone contact end. The release rate adopts such a gradient design to maintain the local drug concentration, improve the drug utilization efficiency, and provide personalized treatment.

[0037] As described above, the mounting structure 31 is located on the surface, inside, or on the surface and inside of the integrated artificial bone tissue complex 3. As an example, Figures 1 to 3As shown, the mounting structure 31 can be a cavity structure, and the cavity structure has at least one port connected to the outer surface of the integrated artificial bone tissue complex 3, so as to facilitate the placement of a sustained-release system outside the integrated artificial bone tissue complex 3, and also facilitate the bone growth promoting materials and / or drugs in the sustained-release system to seep out and contact with bone tissue.

[0038] Furthermore, micropores 33 can be designed on the bioactive material 1. The structure of the micropores 33 can allow bone tissue to grow into the micropores 33. The pore size and porosity of the micropores 33 meet the requirements of biomechanics and bone tissue regeneration. Preferably, the opening rate of the micropores 33 on the bioactive material 1 is 50% to 80%, and the pore size is 100 μm to 500 μm. It should be noted that the specific shape of the micropores 33 is not limited, and can be Figure 1 The square holes shown in the figure may also be holes of other shapes, such as round holes, or the entire bioactive material 1 may be designed to be in a sponge-like shape, with the holes on the sponge serving as micropores 33, such as Figure 1 and Figure 4 The black dots in the bioactive material 1 shown in FIG. 1 are micropores 33 .

[0039] Figure 6 The cross-sectional structure of a grid-like mechanical support bracket is shown. The middle part of the mechanical support bracket 2 is hollow, forming an inner hole 21. The inner hole 21 runs through the top and bottom of the mechanical support bracket 1. By designing the inner hole 21, the drug delivery speed in the length direction of the artificial bone can be accelerated, and the growth of bones and blood vessels can also be facilitated. The support structure inside the mechanical support bracket 2 is composed of plates connected to each other, or plates and rods connected to each other. It should be noted that a mounting structure 31 can be opened on the plate of the mechanical support bracket 2, and the bioactive material 1 can be covered on the surface of the plate of the mechanical support bracket 2.

[0040] See also Figure 1 , Figure 4 , shows the cross-sectional structure of an artificial bone tissue complex formed by filling a bioactive material in a mechanical support scaffold provided in this embodiment, and the integrated artificial bone tissue complex 3 has at least a two-layer structure. Furthermore, the integrated artificial bone tissue complex 3 is provided with a plurality of channels 32 for blood vessel growth, the channels 32 are in the same direction as the inner hole 21, and both penetrate the top and bottom of the mechanical support scaffold 1, the channels 32 are relatively thinner than the inner hole 21, and the channels 32 and the inner hole 21 are interconnected through micropores 33, and are connected to the outer surface of the artificial bone tissue complex 3.

[0041] This embodiment also provides a method for making an engineered composite artificial bone, comprising the following steps:

[0042] Prepare the mechanical support bracket 2 by using a specific mold forming technology or a 3D printing technology;

[0043] The mechanical support bracket 2 is surface treated to form an uneven morphology on the surface of the mechanical support bracket 2 so as to form a tight combination with the bioactive material 1. For example, this can be achieved by spraying, laser etching, chemical corrosion, coating treatment and other treatment methods.

[0044] By high temperature sintering or 3D printing or plasma spraying or filling and curing, the mechanical support scaffold 2 is combined with the bioactive material 1 to form an artificial bone tissue complex 3;

[0045] During the process of manufacturing the artificial bone tissue complex 3, or on the surface and / or inside of the manufactured bone tissue scaffold complex 3, a pore structure 31 is manufactured;

[0046] A sustained-release system containing bone growth promoting materials and / or drugs with different functions is embedded into the porous structure 31 .

[0047] In summary, the composite artificial bone of this embodiment has at least the following advantages compared with traditional bone repair materials:

[0048] 1. Mechanical support The scaffold 2 can provide sufficient mechanical support to meet the load requirements during bone repair.

[0049] 2. After the mechanical support scaffold 2 is combined with the bioactive material 1, its integration with bone tissue can be enhanced. At the same time, these bioactive materials can gradually degrade during use, and the degradation rate matches the bone healing rate, avoiding the impact of long-term residual artificial materials on bone tissue; the bone integration effect reaches the optimal state through the natural biological reaction with the bone tissue.

[0050] 3. The carrying structure can carry a sustained-release system, which contains bone growth-promoting materials and / or drugs. The bone growth-promoting materials and / or drugs in the sustained-release system are continuously and slowly released, which can accelerate bone healing and repair.

[0051] 4. Referring to Figure 7a and Figure 7b, it has different functions in different application scenarios, providing new solutions for repairing large-area bone defects, filling and supporting bone structures, and areas that require long-term weight-bearing.

[0052] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions and improvements made within the spirit and principles of the present invention should be included in the protection scope of the present invention.

Claims

1. An engineered composite artificial bone, characterized in that: It includes a bioactive material and a mechanical support scaffold; the bioactive material is the main body, and the mechanical support scaffold is contained inside the bioactive material, and they are tightly combined with each other to form an engineered one-piece artificial bone tissue complex; the mechanical support scaffold is used to provide mechanical support for the one-piece artificial bone tissue complex to meet the load requirements during bone repair.

2. The engineered composite artificial bone according to claim 1, characterized in that: The mechanical support bracket is a honeycomb, bifurcated, grid, fence or tree branch structure; The mechanical scaffold is a biodegradable composite scaffold or a non-degradable scaffold.

3. The engineered composite artificial bone according to claim 1, characterized in that: The surface and / or interior of the artificial bone tissue complex is equipped with a bone growth promoting material release system and / or a drug release system.

4. The engineered composite artificial bone according to claim 3, characterized in that: The surface and / or interior of the integrated artificial bone tissue complex is provided with a carrying structure, and the carrying structure is used to accommodate the bone growth promoting material release system and / or the drug release system; Alternatively, the bone growth promoting material release system and / or the drug release system is coated on the surface of the carrying structure.

5. The engineered composite artificial bone according to claim 4, characterized in that: The mounting structure is a cavity structure; The cavity structure is located on the surface of the integrated artificial bone tissue complex; Alternatively, the cavity structure is connected from the surface of the integrated artificial bone tissue complex to the interior of the artificial bone tissue complex.

6. The engineered composite artificial bone according to any one of claims 3 to 5, characterized in that: The release rate of the release system is designed in a gradient, wherein the release rate of the bone growth promoting material and / or drug near the bone contact end is greater than the release rate of the bone growth promoting material and / or drug far from the bone contact end.

7. The engineered composite artificial bone according to any one of claims 3 to 5, characterized in that: The bone growth promoting material release system and / or drug release system comprises at least one of a coating on the outer surface of the integrated artificial bone tissue complex, and a microsphere and microcapsule release system located in the carrying structure.

8. The engineered composite artificial bone according to claim 1, characterized in that: The bioactive material is provided with micropores for bone tissue to grow into, the opening rate of the micropores on the bioactive material is 50% to 80%, and the pore diameter is 100 μm to 500 μm.

9. The engineered composite artificial bone according to claim 1, characterized in that: The integrated artificial bone tissue complex is provided with a channel inside for blood vessels to grow in and for providing a growth space for bone tissue, and the channel is connected to the outer surface of the integrated artificial bone tissue complex.

10. A method for producing an engineered composite artificial bone according to any one of claims 1 to 9, characterized in that: The following steps are involved: preparing a mechanical support scaffold; Performing surface treatment on the mechanical support bracket; The mechanical support scaffold is combined with the bioactive material through high temperature sintering or 3D printing or plasma spraying or filling and curing to form an integrated artificial bone tissue complex; Making a mounting structure on the surface and / or inside of the integrated bone tissue complex; A sustained-release system containing bone growth promoting materials and / or drugs with corresponding functions is embedded into the carrying structure.

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