CN104707182B - Intervertebral implant - Google Patents

Abstract

An intervertebral implant, in particular, a kind of porous hydroxyapatite as a scaffold model filled with metal powder and then sintered to form a partially degradable hydroxyapatite/metal block The intervertebral implant gradually degrades the hydroxylapatite structure as it is implanted into the human body, and guides the bone tissue to cling to the inside of the porous metal, forming a stable upper and lower bone fusion effect.

Description

Intervertebral implant

technical field

The invention relates to the technical field of medical implants, in particular to a partially degradable and porous intervertebral implant, which is used to form partially degradable hydroxyl apatite and metal mixed blocks material, so as to guide bone regeneration and form the effect of stabilizing the fusion of upper and lower bones.

Background technique

Press, lumbar interbody fusion, which means removing the intervertebral disc from two vertebrae and then fusing the two together. This procedure is also known as "spinal fusion". It is usually used to treat patients with persistent back pain, sciatica or weakness of legs caused by spinal diseases such as degenerative spondylosis and herniated disc. Spinal fusion is also an important part of the surgery to correct spinal deformities such as scoliosis, spondylolisthesis or spinal trauma.

It would be of great practical benefit if implants for bone repair (or implants for bone repair) were bioabsorbable while providing support. Existing spinal fusion devices consist of a metal framework with bioabsorbable material placed therein, such as the device shown in US Patent No. 5,645,598. However, these implant systems used to restore bone tissue are placed between two vertebrae, but the hardness of the implant itself is not enough and the relative volume is smaller than the vertebrae, which causes the implant to sink, and wear or even destroy each other It destroys the bone tissue between the vertebrae, especially the end plane of the vertebrae, causing serious damage.

In addition, scaffolds currently used in tissue engineering techniques (mostly made of biodegradable polymers) have a porous structure that allows living cells (usually taken from patients under treatment) to infiltrate the structure during cell culture. After a period of cell culture, the cellular scaffold is implanted in an immune-depleted animal (such as a rat) or in the patient himself (usually subcutaneously for subsequent manipulations). During this period (weeks to months) the cells rapidly multiply by absorbing nutrients provided by the animal or patient, while the scaffold itself gradually dissolves and absorbs. Afterwards, the implant (a real bone tissue) is removed from under the animal's or patient's skin and reimplanted in the (injured or diseased) area requiring treatment. For example, those described in US6,139,578; US6,200,606; US5,306,303 and US6,132,463.

However, if the scaffold used in tissue engineering technology is bioabsorbable, has sufficient porosity and can provide support at the same time, then such a material has great advantages. Wherein as Chinese patent CN 119346A: a kind of porous calcium phosphate bone cement containing pore-forming agent is characterized in that it is made up of conventional calcium phosphate bone cement and pore-forming agent, and said pore-forming agent is slightly soluble salt, acid One or more of formula salts and basic salts or surfactants. However, it is an unfixed bone cement with poor mechanical strength and cannot be used alone as a bone fusion.

Another example is Chinese patent CN 101099873A: a production process of porous magnesium/hydroxyapatite, which is characterized in that hydroxyapatite powder and magnesium powder are mixed in proportion, cold-pressed, and then sintered, and magnesium is generated at high temperature. Vaporization and evaporation make hydroxyapatite porous. However, after the magnesium is removed at high temperature, only the porous HA remains, which also has the problem of poor mechanical strength.

Another example is Chinese patent CN 101797400A: a porous degradable magnesium alloy bone scaffold material containing HA nanopowder, characterized in that the porous degradable magnesium alloy bone scaffold material is composed of magnesium powder, HA Nano powder, and pore-forming agent, in the mid-term, magnesium-zinc alloy powder is 50-80%, HA nano-powder is 10-20%, pore-forming agent is composed, of which, magnesium-zinc alloy powder is 50-80%, HA nano-powder 10-20% for the pore-forming agent and 10-30% for the pore-forming agent. However, after the magnesium is removed at high temperature, only the porous HA remains, which also has the problem of poor mechanical strength.

Furthermore, conventional high-temperature (usually >1000 °C) sintered porous hydroxyapatite (HA) materials do not have sufficient micro/nano-scale pores and are difficult to be absorbed by organisms. On the other hand, biodegradable polymers conventionally used for scaffolds have the disadvantages of relatively low strength and too high dissolution rate. In other words, under the premise of reducing weight and increasing biological integration, it is necessary to develop connected porous metal medical materials that can promote bone conduction.

In view of the shortcomings derived from the above-mentioned interconnected porous metal medical materials that promote bone conduction, the inventor of this case desperately wanted to improve and innovate, and finally successfully developed and completed this intervertebral implant.

Contents of the invention

The object of the present invention is to provide a kind of intervertebral implant, thereby can form the intervertebral implant of locally degradable hydroxyapatite/metal blocks, the hydroxyapatite The structure gradually degrades, and guides the bone tissue to cling to the inside of the porous metal, forming a stable upper and lower bone fusion effect.

The second object of the present invention is to provide an intervertebral implant, which is a degradable polymer material or composite made of ceramic material or metal material, designed and manufactured according to the principle of bionics with excellent performance and structure, and has a regulating material the degradation rate.

Another object of the present invention is to provide a scaffold material with the biological behavior and culture efficiency of cells, which can be well adapted, combined and repaired with the human body cavity after the intervertebral implant is implanted. thing.

Another object of the present invention is to provide an intervertebral implant with good biocompatibility, which has no cytotoxicity when cultured in vitro, and will not cause human bone rejection when implanted in the human body Advantages of the response.

Another object of the present invention is to provide an intervertebral implant, which has a three-dimensional structure and has a highly porous structure. The intervertebral implant has a large inner surface area to facilitate The implantation and adhesion of cells are also conducive to the infiltration of cell nutrients and the discharge of metabolites.

Another object of the present invention is to provide an intervertebral implant, which has good surface activity, can promote cell adhesion and provide a good microenvironment for cell proliferation on its surface.

An intervertebral implant that can achieve the purpose of the above invention is to use porous HA as the scaffold model to fill in metal powder and then sintered to form a partially degradable HA/metal block The intervertebral implant of material, its preparation method, comprises the steps:

Step a, mixing: stirring the biodegradable biomaterial that can degrade in the human body and the adhesive liquid to form a slightly viscous liquid;

Step b, coating: coating the above-mentioned slightly viscous liquid with a porous polymer scaffold, so that the surface of the polymer scaffold and/or its cavity-like space is coated with the slightly viscous liquid;

Step c, drying and shaping: and drying after the coating is completed, so that the slightly viscous liquid is tightly coated on the polymer support and the cavity-like space, and the original porous arrangement of the polymer support and the cavity-like space is different , tightly coated on the surface to present the same porous arrangement;

Step d, sintering removal: high-temperature sintering in an atmospheric furnace to remove the polymer scaffold and the adhesive to obtain a porous biodegradable biomaterial scaffold; and

Step e, filling and winding: use the degradable biomaterial scaffold to fill the scaffold model with metal powder, and perform vacuum high-temperature sintering to obtain an intervertebral implant made of degradable biomaterial and metal powder. .

Thereby, through the specific realization of the above-mentioned technical means, the permeable HA biomaterial of the present invention has good biocompatibility, osteoconductivity and biodegradability, and the HA/metal block The intervertebral implant can gradually dissolve and biodegrade after a certain period of time. After a certain period of time, the non-living hydroxyapatite intervertebral implant gradually dissolves and disappears, and is replaced by living new bone tissue. Hydrogen The intervertebral implant of oxyapatite/metal block is implanted in the human cavity, and the bone tissue is gradually guided to grow after the intervertebral implant of hydroxyapatite/metal block is implanted in the cavity of the human body. Into the cavity-like space, and at the same time prevent the growth of soft tissue, so as to realize the firm mechanical integration of the intervertebral implant of HA/metal block in human bone, and can effectively increase the added value of the product, and improve its economic efficiency.

Description of drawings

Fig. 1 is a brief flow diagram of an intervertebral implant of the present invention;

Fig. 2 is that the step of this a kind of intervertebral implant is made schematic diagram;

Figures 3 to 6 are diagrams showing the normal behavior of cells spread on the surface of the porous metal structure.

detailed description

Please refer to Figure 1, an intervertebral implant provided by the present invention is composed of metal powder and degradable biomaterial; wherein, the degradable biomaterial has a plurality of communicating holes after sintering, and the metal powder The body is filled in the plurality of communicating holes, and is sintered to interfit with the degradable biomaterial. In this way, the degradable biomaterial contained in the intervertebral implant can dissolve through body fluids and cell-mediated biodegradation, part of which participates in the local or remote bone tissue reconstruction of bone tissue implantation, and the other part is gradually excreted by the metabolic system In vitro, the defect site is finally completely replaced by new bone tissue, and the metal scaffold also acts as a permanent scaffold, that is, bone tissue engineering scaffold material. Based on this, the degradable biological material can also be replaced by absorbable biological material, so as to achieve the above-mentioned effect according to the same principle.

Continuing to refer to Figures 1 and 2, the intervertebral implant is made by the following steps, including: step a, mixing: stirring the degradable biomaterial that can degrade in the human body and the adhesive liquid, the stirring temperature 1100～1300℃, stirring and mixing time is 10～60min to form a slightly viscous liquid; among them, the degradable biomaterial can be selected as hydroxyapatite, and the adhesive can be selected as polyvinyl acetate Ester (also known as polyvinyl acetate, referred to as PVA, PVAc), which belongs to a kind of elastic synthetic polymer, preferably, this embodiment is mixed with polyvinyl acetate by hydroxyl apatite to form Hydroxyapatite/PVA slurry as shown in Figure 2;

Step b. Coating: The porous polymer support (high-molecular support) is coated with the above-mentioned slightly viscous liquid, and the surface of the polymer support and/or the cavity-like space is coated with the slightly viscous liquid ; Wherein the polymer scaffold is made of ceramic material or metal material, and the polymer scaffold as shown in Figure 2 has a plurality of cavity-like spaces;

Step c. Drying and setting: After finishing the coating, dry in an oven at a temperature of 50-100°C and a drying and setting time of 8-24 hours, so that the slightly viscous liquid can be tightly coated on the surface of the polymer support and /or cavity-like space, and depending on the original porous arrangement of the polymer scaffold and/or cavity-like space, it is tightly covered on the surface to present the same porous arrangement; preferably, this embodiment uses the polymer scaffold to adhere After the hydroxylapatite/PVA slurry, the surface of the polymer scaffold and the cavity-like space are coated with the aforementioned slurry, and arranged in a porous form;

Step d, sintering removal: Carry out high-temperature sintering in an atmospheric furnace, the high-temperature sintering temperature is 1100-1300°C, and remove the polymer scaffold and adhesive, and then obtain a porous biodegradable biomaterial scaffold, see Figure 2 for details ;as well as

Step e, filling and winding: using a porous degradable biomaterial support to fill the support mounting model with metal powder, wherein the support mounting model of the degradable biomaterial support can have a three-dimensional structure of interconnected holes, and the degradable biomaterial support The wire diameter structure width of the stent model is 10 μm to 200 μm, and the metal powder can be selected from titanium, titanium alloy, zirconium, zirconium alloy, tantalum, tantalum alloy or a mixture of more than one that can be prepared by sintering. And after the metal powder is sintered, it presents a uniform metal sphere structure size, which is equal to the particle size of the metal powder before sintering, and the particle size of the metal powder is between 10 μm and 100 μm; when the metal powder is filled into the polymer support Afterwards, vacuum high-temperature sintering is carried out, and the vacuum high-temperature sintering temperature is controlled at 1100-1300 °C compared with the family, and the drying and setting time is 1-3 hours, so as to obtain the intervertebral implant in which the degradable biomaterial and metal powder are embedded with each other. Injection; Preferably, the present embodiment is to obtain a block structure that can be sintered together with metal as shown in Figure 2 (a porous metal structure that is partially degradable and guides the regeneration of the drawing ), the block is the porous intervertebral implant of the present invention.

In this way, through the above preparation method, the intervertebral implant of HA/metal block can be implanted into the cavity of the human body to ensure that the bone tissue can gradually grow into the cavity after the intervertebral implant is implanted. shape space, in which HA is a degradable material implanted in the human body. The material structure of HA material is the key factor to determine its biodegradability. Calcium of HA Phosphorus ratio (Ca/P) is 1.65-1.75. After sintering, it still maintains the structure of apatite (apatite), which produces bone conduction in the process of new bone formation, and slowly degrades with the increase of implantation time. During the rapid degradation process, the excellent bone conduction effect of HA can be used to guide new bone tissue from the host bone along the HA/metal block intervertebral implant into HA /Inside the intervertebral implant of the metal block, it achieves the effect of stable healing of the upper and lower bone tissues and a firm mechanical fixation.

In summary, through the aforementioned structural design, the present invention can prepare a porous metal structure, so as to form an intervertebral implant of locally degradable HA/metal block, and then implant it During the time of entering the human body, the hydroxyl apatite structure gradually degrades, and during the degradation process, the bone tissue is guided to cling to the inside of the porous metal structure, so that the implanted part forms a stable upper and lower bone fusion effect, so that It further has the effect of facilitating and increasing biological conjugation.

A kind of intervertebral implant provided by the present invention has the following advantages when compared with the aforementioned cited cases and other conventional technologies:

The intervertebral implant of hydroxyapatite/metal block is biodegradable, and the intervertebral implant should be gradually degraded during the formation of bone tissue without affecting the structure and function of newly formed bone tissue .

The intervertebral implant of the hydroxyapatite/metal block has plasticity, can be processed into a desired shape and has a certain mechanical strength, and can still be maintained for a certain period of time after the intervertebral implant its shape and give the newly formed tissue the shape it was designed for.

The above detailed description is a specific description of a feasible embodiment of the present invention, but this embodiment is not used to limit the patent scope of the present invention, and any equivalent implementation or change that does not depart from the technical spirit of the present invention shall include within the patent scope of this case.

To sum up, this case is not only innovative in terms of space type, but also can enhance the above-mentioned multiple functions compared with commonly used items. It should have fully met the statutory requirements for a novelty and progressive invention patent. I would like to file an application in accordance with the law. I sincerely request your office Approval of this invention patent application to encourage inventions is very grateful.

Claims (3)

1. An intervertebral implant, characterized in that: it is composed of metal powder and degradable biomaterial; Wherein, the degradable biomaterial is sintered to have a plurality of communicating holes, and the metal powder is filled in the plurality of communicating holes, and is sintered to interfit with the degradable biomaterial; The degradable biomaterial is a scaffold model formed by sintering hydroxylapatite and an adhesive, and the scaffold model has the plurality of interconnected holes; the wire diameter structure width of the scaffold model is 10 μm to 200 μm; After the metal powder is sintered, it presents a uniform metal sphere structure size, which is equal to the particle size of the metal powder before sintering, and the particle size of the metal powder is between 10 μm and 100 μm. 2. The intervertebral implant according to claim 1, wherein the metal powder is at least one selected from titanium, titanium alloy, zirconium, zirconium alloy, tantalum and tantalum alloy. 3. A method for preparing the intervertebral implant as claimed in claim 1, characterized in that: the method comprises the steps of: Step a, mixing: stirring the biodegradable biomaterial that can degrade in the human body and the adhesive liquid to form a slightly viscous liquid; Step b, coating: coating the slightly viscous liquid with a porous polymer scaffold, so that the surface of the polymer scaffold and/or its cavity-like space is coated with the slightly viscous liquid; Step c, drying and shaping: and drying after the coating is completed, so that the slightly viscous liquid is tightly coated on the surface of the polymer bracket and/or the cavity-like space, and the surface of the polymer bracket and/or the cavity The original porous arrangement of the space is different, but it is tightly covered on the surface and presents the same porous arrangement; Step d, sintering removal: high-temperature sintering in an atmospheric furnace to remove the polymer scaffold and the adhesive to obtain a porous biodegradable biomaterial scaffold; and Step e, filling and winding: use the degradable biomaterial scaffold to fill the scaffold model with metal powder, and perform vacuum high-temperature sintering to obtain an intervertebral implant made of degradable biomaterial and metal powder. The degradable biomaterial is HA, and the stent model formed by sintering the HA and the adhesive has a plurality of interconnected holes, and the structure width of the wire diameter of the stent model is 10 μm～ 200 μm.