CN214158120U

CN214158120U - Titanium alloy paramagnetic bone scaffold with three-dimensional bionic micro scaffold

Info

Publication number: CN214158120U
Application number: CN202022384860.3U
Authority: CN
Inventors: 钱文伟; 朱诗白; 张啸天; 陈曦; 王一鸥; 李姗妮
Original assignee: Peking Union Medical College Hospital Chinese Academy of Medical Sciences
Current assignee: Peking Union Medical College Hospital Chinese Academy of Medical Sciences
Priority date: 2020-10-23
Filing date: 2020-10-23
Publication date: 2021-09-10
Anticipated expiration: 2030-10-23

Abstract

The utility model discloses a titanium alloy paramagnetic skeleton support with three-dimensional bionical little support, including titanium alloy support body, titanium alloy support body is porous structure, and porous structure has a plurality of sizes, the shape homogeneous phase and the hole that communicates each other, and the inside of each hole has the three-dimensional bionical little support of degradable, and it has the magnetic nanoparticles to fill in the hole of the mutual intercommunication of three-dimensional bionical little support. The utility model discloses an introduce magnetism nanoparticle and magnetic field in the bionical little support of three-dimensional, can provide a good microenvironment for the proliferation of the relevant cell of osteogenesis, differentiation and final sclerotin deposit.

Description

Titanium alloy paramagnetic bone scaffold with three-dimensional bionic micro scaffold

Technical Field

The utility model relates to a biomedical materials technical field, concretely relates to titanium alloy paramagnetic skeleton support with three-dimensional bionical little support.

Background

Femoral head necrosis is a debilitating disease that is highly prevalent and relatively affects young people, and can lead to progressive collapse of the femoral head and subsequent symptomatic coxitis. In the united states, over 2 million new cases of femoral head necrosis are diagnosed each year, whereas in china only non-invasive ONFH patients reach up to 812 million. Although total hip arthroplasty has been satisfactorily used for the treatment of advanced ONFH, it is important for young early ONFH patients to have the ideal hip protection treatment before irreversible femoral head collapse, in view of the mobility requirements, prosthesis life and revision surgery difficulties, to slow the progression of the disease and thus delay or even avoid total hip arthroplasty.

The core decompression, the most commonly used hip protection treatment, can slow the progression of femoral head necrosis to some extent. However, the necrotic area lacks effective mechanical support after decompression, and the method does not solve the problems of angiogenesis, bone reconstruction, articular surface repair, etc. in the necrotic area. To this end, it is necessary to provide a graft or implant to the defect passage after decompression to prevent further collapse of the femoral head. The current clinical commonly used method still has certain limitations, for example, the technical requirement for fibula transplantation of anastomotic vessels is high, the surgical wound is large, and the problems of fibula related complications, enough transplantable bones, implantation survival rate and the like influence the final treatment effect; in addition, for example, the tantalum rod of Jiemei company has the problems of lack of bone ingrowth (only 1.9 percent) in the tantalum rod, insufficient supporting force, stress fracture caused by strength reduction of the greater trochanter part of the femur and the like.

The titanium alloy is one of biomedical metal functional materials and widely applied to human body external implants, such as oral implants, bone defect repair materials, prosthetic joint implants and the like. The titanium alloy stent has the advantages of no toxicity, light weight, good biocompatibility and corrosion resistance and elastic modulus more matched with human cortical bone, so that the porous titanium alloy stent modified by the surface coating is more and more concerned. Although the implantation of the porous titanium alloy stent is beneficial to the growth of peripheral bones to a certain extent, the pore diameter of the currently applied 3D printing titanium alloy stent is more than 500-1500 mu m, and the porous titanium alloy stent is obviously too spacious for the diameter of 15-25 mu m on average. And the small aperture will increase the proportion of metal, which is not in accordance with the requirements of tissue engineering. In addition, titanium is a biologically inert material and lacks interaction with surrounding tissue after implantation in the body. Therefore, the titanium alloy scaffold can only provide a carrier for creeping replacement of new bone tissues, cannot promote bone regeneration, cannot achieve good biomechanical stability, needs to optimize and modify the internal structure thereof so as to have good osteoconductivity and osteoinductivity, and provides a good environment for new blood vessels and bone regeneration.

The previous researches on the modification of the porous titanium alloy material comprise chemical treatment, bioactive coating, adhesion of various growth factors on the surface, stem cells and the like, but unfortunately, the measures are mostly concentrated on the two-dimensional level of the inner surface of the hole, and the cells can only grow in a two-dimensional space on the hole wall and cannot realize the three-dimensional level filling growth in the whole hole. In view of this, the related art proposes to establish a three-dimensional micro-scaffold with a biomimetic structure in each pore of the porous titanium bone scaffold to provide a good microenvironment for proliferation and differentiation of osteoblast-related cells and final bone deposition. Bone is a unique connective tissue composed of several cellular components and a bone matrix composed of organic and inorganic components, with collagen and hydroxyapatite as the main constituent materials of both components. Bone can therefore be considered as a typical composite material of natural inorganic (nano-hydroxyapatite) -organic (collagen fibers). On the basis, collagen (gelatin) and nano hydroxyapatite are taken as main components of the bionic three-dimensional micro-scaffold in the related prior art. However, the osteogenic and angiogenetic capabilities of such biomimetic three-dimensional scaffolds are still limited.

In view of the above problems in the prior art, there is a need in the art for a paramagnetic bone scaffold of titanium alloy with three-dimensional bionic micro-scaffold capable of providing an optimal environment for proliferation and differentiation of bone formation-related cells.

SUMMERY OF THE UTILITY MODEL

In view of this, an object of the embodiments of the present invention is to provide a paramagnetic bone scaffold of titanium alloy with a three-dimensional bionic micro-scaffold, which can solve the problems of insufficient osteogenic and vascularizing abilities of the existing porous titanium bone scaffold.

Based on the above object, an aspect of the embodiment of the utility model provides a titanium alloy paramagnetic skeleton support with three-dimensional bionical little support, including titanium alloy support body, titanium alloy support body is porous structure, porous structure has a plurality of sizes, the shape is the same and the hole that communicates each other, each the inside of hole has degradable three-dimensional bionical little support, it has magnetic nanoparticles to fill in the hole of three-dimensional bionical little support's mutual intercommunication.

The titanium alloy paramagnetic bone scaffold with the three-dimensional bionic micro scaffold is characterized in that the titanium alloy scaffold body is formed by connecting a plurality of rhombic dodecahedron scaffold units which are communicated with one another, and the inside of each rhombic dodecahedron scaffold unit is provided with one hole.

The paramagnetic skeleton scaffold of titanium alloy with three-dimensional bionic micro-scaffold, preferably, the pore size of the titanium alloy scaffold body is 500-1000 μm.

The paramagnetic skeleton scaffold of the titanium alloy with the three-dimensional bionic micro scaffold preferably has a porosity of 75-85% of the titanium alloy scaffold body.

The paramagnetic bone scaffold of titanium alloy with three-dimensional bionic micro-scaffold is characterized in that the titanium alloy scaffold body is preferably made of Ti6Al4V powder through selective laser melting.

Advantageous effects

1. The utility model provides a titanium alloy paramagnetic skeleton support with three-dimensional bionical little support, its titanium alloy support body prepares into macropore hole and high porosity structure, under the prerequisite of guaranteeing mechanical properties, has not only realized the minimizing of metal, has also realized the maximize that the bone grows into the volume simultaneously, more needn't worry that material degradation and new bone form unmatched problem, provides permanent mechanical support for the necrotic area. In addition, the uniformly communicated hole structure is beneficial to the adhesion and proliferation of bone cells and the growth of capillaries, provides a sufficient space structure for new bone generation, and realizes the matching with normal bone tissues by lower elastic modulus, thereby reducing the stress shielding effect.

2. The utility model provides a titanium alloy paramagnetic skeleton support with three-dimensional bionical little support, it is on the basis of titanium alloy support body, with bone matrix organic component and the most main constitution material gelatin of inorganic composition and hydroxyapatite as the main material, establishes the three-dimensional little support that has bionic structure in the porous structure of titanium alloy support body. The three-dimensional micro-scaffold is not limited by mechanical strength any more, can provide the best growth microenvironment for proliferation and differentiation of cells, and can form autologous bone substitution while collagen and other materials in the scaffold are degraded, so that the best biological fixation is further achieved, and finally the advantage complementation of the two is realized.

3. The utility model provides a titanium alloy paramagnetism skeleton support with three-dimensional bionical micro-support, it has filled the magnetism nanoparticle in the hole of three-dimensional bionical micro-support's mutual intercommunication, introduces this system with magnetism nanoparticle and magnetic field, provides an optimum microenvironment for the proliferation of the relevant cell of osteogenesis, differentiation and final sclerotin deposit, makes this composite support play strongest repairing action to femoral head necrosis.

Drawings

Fig. 1 is a schematic perspective view of a porous structure unit of a titanium alloy paramagnetic bone scaffold with a three-dimensional bionic micro-scaffold according to the present invention;

FIG. 2 is a schematic perspective view of a single-layer titanium alloy stent structure formed by tiling a plurality of porous structural units; and

fig. 3 is a schematic perspective view of a multilayer titanium alloy stent structure formed by tiling and stacking a plurality of porous structure units.

Detailed Description

The following examples are intended to illustrate the invention, but are not intended to limit the scope of the invention. Unless otherwise specified, the technical means used in the examples are conventional means well known to those skilled in the art.

In view of the above, the embodiment of the present invention provides an embodiment of a paramagnetic bone scaffold of titanium alloy with three-dimensional bionic micro-scaffold. Fig. 1 is a schematic perspective view of a porous structural unit of the titanium alloy paramagnetic bone scaffold with the three-dimensional bionic micro-scaffold of the embodiment. Fig. 2 is a schematic perspective view of a single-layer titanium alloy stent structure formed by tiling a plurality of porous structure units. Fig. 3 is a schematic perspective view of a multilayer titanium alloy stent structure formed by tiling and stacking a plurality of porous structure units. As shown in fig. 1 to 3, the paramagnetic bone scaffold of titanium alloy comprises a titanium alloy scaffold body 1, wherein the titanium alloy scaffold body 1 is a porous structure, the porous structure is provided with a plurality of holes 3 which are identical in size and shape and are communicated with each other, a degradable three-dimensional bionic micro scaffold is arranged inside each hole 3, and magnetic nanoparticles are filled in the communicated holes of the three-dimensional bionic micro scaffold.

The titanium alloy stent body 1 is manufactured by adopting a 3D printing technology, has good biocompatibility, high porosity and variable mechanical parameters, and can be used as an ideal filling material in a medullary heart decompression channel. On the premise of ensuring the mechanical strength, the porosity of the titanium alloy stent body 1 is set to be as large as possible to simulate the porous structure of the bone. In addition, the uniformly communicated porous structure is beneficial to the adhesion and proliferation of osteocytes and the growth of capillaries, a sufficient space structure is provided for new osteogenesis, and the titanium alloy support body 1 has low elastic modulus, so that the stress shielding effect can be reduced by matching with normal bone tissues.

Although the titanium alloy stent body 1 has the advantages, the simple titanium bone stent still has the following disadvantages: firstly, the pore diameter of the titanium alloy stent body 1 manufactured to meet the above requirements is generally between 500-1500 μm, and the pores 3 of the titanium alloy stent body 1 are obviously too open for the average diameter of 15-25 μm of the cells; secondly, titanium is a biologically inert material that lacks interaction with surrounding tissues after implantation in the body. In order to solve the problem, the utility model discloses at first, tentatively three-dimensionally modified titanium alloy support body 1, in each hole 3 of titanium alloy support body 1 promptly, establish 3D biomimetic structure's degradable micro-support to provide a good microenvironment for osteoblast's hyperplasia, differentiation and final sclerotin deposit. In particular, considering that collagen and hydroxyapatite are the most important bone matrix constituting materials, having good bone induction and bone conduction capabilities, the present invention uses gelatin and nano hydroxyapatite (nHA) as the main materials of the three-dimensional bionic micro scaffold, and constructs the three-dimensional micro scaffold having a bionic structure in a porous structure by a freeze-drying technique. After the preliminary three-dimensional modification, a porous communicated gelatin extracellular matrix structure is formed inside the holes 3 of the titanium alloy stent body 1 subjected to 3D printing, and similar to a porous structure formed after decalcification of natural bone tissues, the existence of nano hydroxyapatite can be observed around the gelatin holes, and the particle size is about 7-33 μm. Under the field of an electron microscope, the size of 100 holes in the field is measured and counted, and the average value is taken, so that the diameter distribution of the holes of the three-dimensional micro-scaffold is about 70-180 μm.

Through the preliminary three-dimensional modification, the titanium alloy stent body 1 has certain capacity of promoting cell proliferation and differentiation. In order to further promote angiogenesis, the differentiation of osteoblasts to osteoblasts before stimulation and the deposition of extracellular matrix, the utility model also introduces Magnetic Nanoparticles (MNPs) and a magnetic field into the system, and provides an optimal microenvironment for the proliferation and differentiation of osteoblast-related cells and final bone deposition by generating an electromagnetic stimulation effect. The magnetic field can play a role in accelerating fracture healing and osteoblast differentiation and promoting bone formation. Preferably, the hydroxyapatite scaffold or collagen/hydroxyapatite composite scaffold filled with iron oxide nanoparticles exhibits good compatibility with cells differentiated into bone. All three of the above materials can be degraded.

In a preferred embodiment, the titanium alloy stent body 1 is formed by connecting a plurality of rhombic dodecahedron stent units 2 which are communicated with each other, and each rhombic dodecahedron stent unit 2 is internally provided with one hole 3. The rhombic dodecahedron stent unit 2 is used as a unit of a porous structure to form a titanium alloy stent body 1, wherein the pore column of the titanium alloy stent body 1 is 300-800 mu m, the pore diameter is 500-1000 mu m, and the porosity is 75-85%. On the premise of ensuring the mechanical strength, the porosity is set as large as possible so as to provide an effective space for the proliferation and differentiation of cells and the later bone ingrowth. As an example, two titanium alloy scaffolds were fabricated according to the examples and used for in vitro cells (diameter)

Length 2mm) and in vivo animal experiments (diameter)

Length 25-30 mm).

In a preferred embodiment, the titanium alloy stent body 1 is made of Ti6Al4V powder by selective laser melting.

It is obvious to those skilled in the art that the above numerical values are not limited by the embodiments described herein, and those skilled in the art may make modifications according to actual situations as long as they can solve the above technical problems.

To sum up, the utility model discloses an use porous titanium alloy support of 3D printing technique preparation, mechanical stable in structure, have suitable aperture, high porosity, pore intercommunication and elastic modulus and human bone tissue phase-match. Two main components (collagen and nano-hydroxyapatite) of the bone matrix are adopted, and a degradable bionic three-dimensional micro-scaffold is built in each hole of the porous titanium alloy scaffold; and simultaneously, Magnetic Nano Particles (MNPs) and a static magnetic field are introduced to further promote angiogenesis, stimulate differentiation from preosteoblasts to osteoblasts and deposition of extracellular matrix so as to provide an optimal proliferation and differentiation environment for bone formation related cells, thereby constructing the porous titanium alloy orthopedic implant with bioactivity for filling the marrow channel after decompression of the femoral head necrosis core. In the whole system, the porous titanium alloy scaffold is only responsible for providing mechanical strength and serving as a necessary carrier for creeping replacement of the new bone tissue, and the three-dimensional micro scaffold provides a microenvironment similar to that of the normal bone tissue to promote proliferation and differentiation of cells, so that ossification of the new bone tissue is accelerated.

Although the invention has been described in detail with respect to the general description and the specific embodiments, it will be apparent to those skilled in the art that modifications and improvements can be made based on the invention. Therefore, such modifications and improvements are intended to be within the scope of the invention as claimed.

Claims

1. The utility model provides a titanium alloy paramagnetic skeleton support with three-dimensional bionical little support which characterized in that, includes titanium alloy support body, titanium alloy support body is porous structure, porous structure has a plurality of sizes, the shape is the same and the hole that communicates each other, each the inside in hole has the three-dimensional bionical little support of degradable, it has magnetic nanoparticles to fill in the hole of the mutual intercommunication of three-dimensional bionical little support.

2. The paramagnetic bone scaffold of titanium alloy with three-dimensional bionic micro-scaffold, wherein the titanium alloy scaffold body is formed by connecting a plurality of rhombic dodecahedron scaffold units which are communicated with each other, and each rhombic dodecahedron scaffold unit is internally provided with one hole.

3. The titanium alloy paramagnetic bone scaffold with a three-dimensional biomimetic micro-scaffold according to claim 1, wherein the pore size of the titanium alloy scaffold body is 500-1000 μ ι η.

4. The titanium alloy paramagnetic bone scaffold with a three-dimensional biomimetic micro-scaffold according to claim 1, wherein the porosity of the titanium alloy scaffold body is 75-85%.