CN113413250A - Spine repair system for actively inducing bone tissue regeneration fusion and manufacturing method thereof - Google Patents

Abstract

The invention discloses a spine repair system for actively inducing bone tissue regeneration fusion and a manufacturing method thereof, relates to the technical field of biomedical materials, and solves the problem that the existing mature titanium alloy fusion cage has poor spine repair effect. The repair system comprises a titanium alloy porous interbody fusion cage and active ingredients or medicines with the biological function of actively inducing regeneration and fusion of bone tissues, wherein the titanium alloy porous interbody fusion cage is provided with a porous structure, and the porous structure is used for carrying the active ingredients or the medicines. The titanium alloy porous interbody fusion cage is used as a bearing device and a carrier of the repair system, and in-situ slow release is achieved by carrying active ingredients or medicines, so that a directable repair treatment function is given to the titanium alloy porous interbody fusion cage, the biological activity of the repair system is remarkably improved, the repair system has an active bone tissue regeneration induction function, new bones are guided to grow into a defect part, active fusion of the bones is realized, a stable osseous bonding interface between the interbody fusion cage and a vertebral body is formed, and spine repair is realized.

Description

Spine repair system for actively inducing bone tissue regeneration fusion and manufacturing method thereof

Technical Field

The invention relates to the technical field of biomedical materials, in particular to a spine repair system for actively inducing bone tissue regeneration fusion and a manufacturing method thereof.

Background

Spinal injuries including dislocation, fracture, infection, etc. and long-term irregular postures in daily life cause various spinal diseases due to various diseases and accidents. The spinal diseases are not single diseases, but are a general term of disease types, and a series of lumbar intervertebral lesions caused by the spinal diseases belong to the spinal surgical diseases. Patients with spine diseases have dizziness, hand numbness, neck pain, low back pain, cervical spondylosis, intervertebral disc protrusion and arrhythmia, and even paralysis, incontinence of urine and feces and loss of normal living ability, which are serious diseases threatening human health. How to repair and reconstruct the damaged spine is a key problem facing biological and clinical medicine.

In clinical treatment of spinal diseases, spinal fusion is one of the most widely used surgical techniques in spinal surgery, and is promoted mainly by establishing the immediate stabilization of the spine and the osteogenesis, osteoinduction and osteoconductive effects of implants, which are well known to have better curative effects on the diseases. In clinical spinal fusion, the treatment of autogenous and allogeneic bone transplantation has many limitations in material selection, such as limited material sources, increased pain and trauma of patients, and possible immune rejection risk. Therefore, the exploration of the use of biological materials for spinal fusion has been a hot topic of research in the field of material science.

The titanium alloy has good mechanical property, biocompatibility and corrosion resistance, is one of the most widely used materials of the implant in the bone at present, and the titanium alloy interbody fusion cage also becomes the most widely used material of the implant in the spinal fusion. However, most of the titanium alloy fusion cages mature in the market are single bioinert titanium alloy implants, and the improvement on the biological performance of the titanium alloy implants is lacked, so that the fusion cages cannot actively induce the regeneration of bone tissues and actively realize bone fusion, the interface integration effect is poor, and finally the spinal repair effect is poor.

Therefore, it is a technical problem to be solved by those skilled in the art to provide a spinal repair system capable of actively inducing bone tissue regeneration.

Disclosure of Invention

One of the purposes of the invention is to provide a spine repair system for actively inducing bone tissue regeneration and fusing and a manufacturing method thereof, which solve the technical problems that mature titanium alloy fusion cages in the prior art cannot actively induce bone tissue regeneration, cannot actively realize bone fusion, and have poor interface integration effect, thereby causing poor spine repair effect. The various technical effects that can be produced by the preferred technical solution of the present invention are described in detail below.

In order to achieve the purpose, the invention provides the following technical scheme:

the spine repair system comprises a titanium alloy porous interbody fusion cage and an active ingredient or medicament with a biological function of actively inducing bone tissue regeneration fusion, wherein the titanium alloy porous interbody fusion cage is provided with a porous structure, and the porous structure is used for carrying the active ingredient or medicament.

According to a preferred embodiment, the titanium alloy porous interbody cage further comprises a dense force-bearing periphery, and the dense force-bearing periphery is arranged around the porous structure.

According to a preferred embodiment, the titanium alloy porous interbody cage further comprises at least one perfusion opening, the perfusion opening is arranged on the dense force-bearing periphery, and the perfusion opening penetrates through the dense force-bearing periphery and is connected with the porous structure.

According to a preferred embodiment, the porous structure is a gradient porous structure.

According to a preferred embodiment, the pore size of the porous structure is gradually reduced from the inside of the titanium alloy porous interbody cage to the outside.

According to a preferred embodiment, the porosity of the porous structure is 59-93%, and the pore diameter is 550-880 μm; the gradient of the pore diameter is 30 μm, and the gradient of the pore diameter is increased from the inside of the titanium alloy porous interbody fusion cage to the outside.

According to a preferred embodiment, the active ingredient or drug having the biological function of actively inducing bone tissue regeneration fusion is nano-hydroxyapatite, bone morphogenetic protein 2 or zoledronic acid.

The manufacturing method of the spine repair system for actively inducing bone tissue regeneration fusion in any technical scheme of the invention comprises the following steps:

reconstructing upper and lower vertebral body models of a part to be repaired according to the CT data;

analyzing parameters of the upper and lower vertebral body models of the part to be repaired, and constructing a macroscopic appearance of the titanium alloy porous interbody fusion cage;

analyzing the stress of the titanium alloy porous interbody fusion cage, and constructing a porous structure of the titanium alloy porous interbody fusion cage;

constructing a perfusion opening of the titanium alloy porous interbody cage;

preparing the titanium alloy porous interbody fusion cage by using a selective laser melting 3D printing technology;

filling and carrying active ingredients or medicines with the biological function of actively inducing bone tissue regeneration and fusion into the porous structure of the titanium alloy porous interbody fusion cage through a filling opening;

freeze-drying the composite perfusion slurry, and storing the active ingredient or the medicine.

According to a preferred embodiment, the method for loading the active ingredient or the medicine with the biological function of actively inducing the bone tissue regeneration fusion into the titanium alloy porous interbody fusion cage through the perfusion opening comprises the following steps:

mixing 3-5 wt% sodium alginate water solution with active component or medicine;

after being uniformly mixed, a sufficient amount of the mixture is sucked by a syringe and injected into the titanium alloy porous interbody fusion cage through the perfusion opening;

placing the titanium alloy porous interbody fusion cage into 5-10 wt% of CaCl₂And (3) crosslinking for 3-12 hours in the solution to enable the sodium alginate to gel.

According to a preferred embodiment, the method for preserving the active ingredient or drug is:

and (3) putting the titanium alloy porous interbody fusion cage after the sodium alginate is gelatinized into the gel into a freeze dryer, and freeze-drying for 12-24 hours in vacuum to remove the water in the hydrogel.

The spine repair system for actively inducing bone tissue regeneration fusion and the manufacturing method thereof provided by the invention at least have the following beneficial technical effects:

the invention relates to a spine repair system for actively inducing bone tissue regeneration fusion, which comprises a titanium alloy porous interbody fusion cage and active ingredients or medicaments with the biological function of actively inducing bone tissue regeneration fusion, wherein, the titanium alloy porous interbody fusion cage has a porous structure, and the porous structure is used for carrying active ingredients or medicines, the invention actively induces the bone tissue regeneration and fuses the spinal column repair system, takes the titanium alloy porous interbody fusion cage as a bearing device and a carrier, the in-situ slow release is achieved by carrying active ingredients or medicines, a titanium alloy porous interbody fusion cage is endowed with a directable repair treatment function, the biological activity of the repair system is remarkably improved, the function of actively inducing bone tissue regeneration is achieved, new bones are guided to grow into defect parts, active bone fusion is achieved, a stable bony combination interface between the interbody fusion cage and a vertebral body is formed, and spine repair is achieved.

The manufacturing method of the spine repair system for actively inducing bone tissue regeneration fusion in any technical scheme of the invention comprises the steps of designing an intervertebral fusion cage model with a pourable opening structure and a macroscopic porous structure through parametric modeling, forming by utilizing a laser selective fusion 3D printing technology, and then loading active ingredients or medicaments into the intervertebral fusion cage through a pouring port, so that the bioactivity of the repair system can be obviously improved, the spine repair system has the function of actively inducing bone tissue regeneration, guiding new bones to grow into defect parts, realizing bone active fusion, forming a stable osseous bonding interface between the intervertebral fusion cage and vertebral bodies, and realizing spine repair.

The spine repair system and the manufacturing method thereof for actively inducing bone tissue regeneration fusion solve the technical problems that mature titanium alloy fusion cages in the prior art cannot actively induce bone tissue regeneration, cannot actively realize bone fusion, and have poor interface integration effect, so that the spine repair effect is poor.

Drawings

In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the embodiments or the prior art will be briefly described below, it is obvious that the drawings in the following description are only some embodiments of the present invention, and for those skilled in the art, other drawings can be obtained according to the drawings without creative efforts.

FIG. 1 is a first schematic view of a first preferred embodiment of an actively induced bone tissue regeneration fusion spinal repair system according to the present invention;

FIG. 2 is a second schematic view of a first preferred embodiment of the spinal repair system with actively induced bone tissue regeneration fusion according to the present invention;

FIG. 3 is a schematic representation of a first pore size of the porous structure of the present invention;

FIG. 4 is a schematic representation of a second pore size of the porous structure of the present invention;

FIG. 5 is a schematic representation of a third pore size of the porous structure of the present invention;

FIG. 6 is a schematic view of a second preferred embodiment of the spinal repair system with actively induced bone tissue regeneration fusion according to the present invention;

FIG. 7 is a schematic view of a third preferred embodiment of the spinal repair system with actively induced bone tissue regeneration fusion according to the present invention;

FIG. 8 is a schematic view of a fourth preferred embodiment of the spinal repair system with actively induced bone tissue regeneration fusion according to the present invention;

fig. 9 is a schematic view of a fifth preferred embodiment of the spinal repair system for actively inducing bone tissue regeneration fusion according to the present invention.

In the figure: 101. a porous structure; 102. the periphery of the bearing is compact; 103. a pour opening; 104. a bone graft region.

Detailed Description

In order to make the objects, technical solutions and advantages of the present invention more apparent, the technical solutions of the present invention will be described in detail below. It is to be understood that the described embodiments are merely exemplary of the invention, and not restrictive of the full scope of the invention. All other embodiments, which can be derived by a person skilled in the art from the examples given herein without any inventive step, are within the scope of the present invention.

The spine repair system for actively inducing bone tissue regeneration fusion and the manufacturing method thereof according to the present invention will be described in detail with reference to the accompanying drawings 1 to 9 and examples 1 to 8 of the specification.

The invention relates to a spine repair system for actively inducing bone tissue regeneration fusion, which comprises a titanium alloy porous interbody fusion cage and active ingredients or medicines with the biological function of actively inducing bone tissue regeneration fusion. Preferably, the titanium alloy porous intervertebral fusion device has a porous structure 101, and the porous structure 101 is used for carrying active ingredients or medicines, as shown in figures 1-9. Preferably, the active ingredient or drug having the biological function of actively inducing the bone tissue regeneration fusion is nano-hydroxyapatite, bone morphogenetic protein 2(BMP2) or zoledronic acid. Without being limited thereto, the active ingredient or drug may be of the remaining type. The spine repair system for actively inducing bone tissue regeneration fusion, disclosed by the invention, has the advantages that the titanium alloy porous interbody fusion cage is used as a force bearing device and a carrier, and the in-situ slow release is realized by carrying active ingredients or medicaments, so that a directable repair treatment function is given to the titanium alloy porous interbody fusion cage, the biological activity of the repair system is obviously improved, the spine repair system has an active bone tissue regeneration inducing function, new bones are guided to grow into a defect part, the active fusion of the bones is realized, a stable bony combination interface between the interbody fusion cage and a vertebral body is formed, and the spine repair is realized. The spine repair system for actively inducing bone tissue regeneration and fusing solves the technical problems that a mature titanium alloy fusion cage in the prior art cannot actively induce bone tissue regeneration, cannot actively realize bone fusion, has poor interface integration effect and causes poor spine repair effect.

According to a preferred embodiment, the titanium alloy porous interbody cage further comprises a dense force-bearing periphery 102, the dense force-bearing periphery 102 being disposed around the porous structure 101. As shown in fig. 1, fig. 2, fig. 6, fig. 7 or fig. 9, the dense force-bearing periphery 102 is provided around the porous structure 101, excluding the upper and lower sides of the porous structure 101, so that the active ingredient or drug carried in the porous structure 101 can be released from the upper and lower sides of the porous structure 101 to act thereon. The titanium alloy porous interbody fusion cage in the preferred technical scheme of the embodiment further comprises a dense force-bearing periphery 102, and the dense force-bearing periphery 102 is arranged around the porous structure 101, so that on one hand, the dense force-bearing periphery 102 is more dense in structure and can be used as a force-bearing part, and on the other hand, the titanium alloy porous interbody fusion cage can also play a role in fixing and protecting the porous structure 101.

According to a preferred embodiment, the titanium alloy porous interbody cage further comprises at least one perfusion opening 103, the perfusion opening 103 is arranged on the dense force-bearing periphery 102, and the perfusion opening 103 penetrates the dense force-bearing periphery 102 and is connected with the porous structure 101. Preferably, the filling opening 103 is cylindrical, and the radius of the filling opening 103 is 1-5 mm, and the length is 10-20 mm. In the preferred technical scheme of the embodiment, the filling opening 103 is arranged on the dense force-bearing periphery 102 so as to facilitate the filling of the active ingredient or the medicine into the porous structure 101. The number of the pouring openings 103 may be four, respectively located on four sides of the dense stressed periphery 102, as shown in fig. 1, 2, 6 or 7; the number of irrigation openings 103 may also be 1, located on either side of the dense stressed periphery 102, as shown in fig. 9.

According to a preferred embodiment, the porous structure 101 is a gradient porous structure. Preferably, the pore size of the porous structure 101 is gradually reduced from the inside of the titanium alloy porous intervertebral cage to the outside. More preferably, the porosity of the porous structure 101 is 59-93%, and the pore diameter is 550-880 μm; the gradient of the pore diameter is 30 μm, and the gradient of the pore diameter is increased from the inside of the titanium alloy porous interbody fusion cage to the outside. As shown in FIGS. 3 to 5, the pore diameters of the titanium alloy porous interbody fusion cage are shown in three sizes from the inside to the outside. For example, the first pore size shown in fig. 3 is located at the center of the porous structure 101, the pore size is 880 μm, and the porosity is 93%; the second aperture shown in fig. 4 is located in the middle of the porous structure 101; the third pore size shown in fig. 5 is located outside the porous structure 101, and the pore size is 550 μm and the porosity is 59%.

The manufacturing method of the spine repair system for actively inducing the bone tissue regeneration fusion in any technical scheme of the invention comprises the following steps:

s1: and reconstructing an upper vertebral body model and a lower vertebral body model of the part to be repaired according to the CT data.

S2: and analyzing parameters of upper and lower vertebral body models of the part to be repaired, and constructing the macroscopic appearance of the titanium alloy porous interbody fusion cage.

S3: and analyzing the stress of the titanium alloy porous interbody fusion cage to construct a porous structure 101 of the titanium alloy porous interbody fusion cage.

S4: the perfusion opening 103 of the titanium alloy multi-porous interbody cage is constructed.

S5: and preparing the titanium alloy porous interbody fusion cage by using a selective laser melting 3D printing technology.

S6: active ingredients or drugs with the biological function of actively inducing bone tissue regeneration and fusion are loaded into the porous structure 101 of the titanium alloy porous interbody fusion cage through the perfusion opening 103.

Preferably, the method for loading the active ingredient or the medicine with the biological function of actively inducing the bone tissue regeneration fusion into the titanium alloy porous interbody fusion cage through the perfusion opening 103 comprises the following steps:

s61: mixing 3-5 wt% sodium alginate water solution with active component or medicine;

s62: after being uniformly mixed, a syringe is used for sucking sufficient amount of the mixture to inject the mixture into the titanium alloy porous interbody fusion cage through the perfusion opening 103;

s63: placing the titanium alloy porous interbody fusion cage into 5-10 wt% of CaCl₂And (3) crosslinking for 3-12 hours in the solution to enable the sodium alginate to gel.

S7: freeze-drying the composite perfusion slurry, and storing the active ingredient or the medicine.

Preferably, the method for preserving the active ingredient or drug is: and (3) putting the titanium alloy porous interbody fusion cage subjected to the gelling of the sodium alginate into a freeze dryer, and carrying out vacuum freeze drying for 12-24 hours to remove water in the hydrogel.

The manufacturing method of the spine repair system with the actively induced bone tissue regeneration fusion in any technical scheme of the invention comprises the steps of designing an intervertebral fusion cage model with a perfusable opening 103 and a macroscopic porous structure 101 through parametric modeling, forming by using a laser selective fusion 3D printing technology, and then loading active ingredients or medicines into the intervertebral fusion cage through a perfusion opening, so that the bioactivity of the repair system can be obviously improved, the spine repair system has the function of actively inducing bone tissue regeneration, guiding new bones to grow into defect parts, realizing bone active fusion, forming a stable osseous bonding interface between the intervertebral fusion cage and vertebral bodies, and realizing spine repair. The invention relates to a manufacturing method of a spine repair system for actively inducing bone tissue regeneration and fusing, which solves the technical problems that a mature titanium alloy fusion cage in the prior art cannot actively induce bone tissue regeneration, cannot actively realize bone fusion, has poor interface integration effect and causes poor spine repair effect.

In addition, the spine repair system for actively inducing bone tissue regeneration fusion and the manufacturing method thereof have the following beneficial effects:

(1) according to the spine repair system for actively inducing bone tissue regeneration fusion, the titanium alloy porous interbody fusion cage is designed into the gradient porous structure 101 with the pore diameter gradually decreasing from the inside to the outside, so that the permeation effect of the titanium alloy porous interbody fusion cage can be conveniently regulated, the flow and filling of active ingredients or medicines from the perfusion opening 103 into the porous structure 101 after perfusion are facilitated, in-situ slow release is realized, the effective action duration of the active ingredients or medicines is prolonged, and bone regeneration fusion is continuously induced.

(2) According to the manufacturing method of the spine repair system for actively inducing bone tissue regeneration fusion, the titanium alloy porous interbody fusion cage is prepared by the 3D printing technology, and the printed product has the advantages of high precision, excellent quality, low cost, short production period, good mechanical property, biocompatibility and corrosion resistance.

(3) According to the manufacturing method of the spine repair system for actively inducing bone tissue regeneration fusion, active ingredients or medicines with the function of actively inducing bone tissue regeneration are injected into the porous structure 101 in the titanium alloy porous interbody fusion cage by blending with hydrogel (sodium alginate aqueous solution), and are preserved by gelling and freeze-drying, so that the effect of in-situ release after implantation is achieved, active fusion of bones is promoted, and compared with the traditional modes such as intravenous injection and oral administration, the spine repair system has the advantages of higher action speed and better effect.

(4) According to the manufacturing method of the spine repair system for actively inducing bone tissue regeneration fusion, the titanium alloy porous interbody fusion cage is prepared by the 3D printing technology, and the structure controllability, the function diversification and the quantitative slow release rate of the repair system can be realized by changing the aperture of the porous structure 101, the shape, the size and the position of the perfusion opening 103, and regulating and controlling the parameters such as the type, the content, the proportion and the like of the loaded active ingredients or medicines, so that the individual requirements of spine repair face are directionally solved.

Example 1

An actively induced bone tissue regeneration fusion spinal repair system constructed by taking an example of a clinical herniated disc patient as an object. The manufacturing method comprises the following specific steps:

(1) and preparing the 3D printing titanium alloy porous interbody fusion cage.

(a) The method comprises the steps of collecting clinical lumbar vertebra CT data of a patient, reading and reconstructing a 4-5 segment model of the lumbar vertebra of the patient, calculating and extracting geometric characteristics through data processing software, and designing a macroscopic appearance structure of the titanium alloy porous interbody fusion cage.

(b) A gradient porous structure 101 of the titanium alloy porous interbody fusion cage is constructed, the innermost pore diameter is 880 mu m, the porosity is 93%, the outermost pore diameter is 550 mu m, the porosity is 59%, and the pore diameter variation gradient is 30 mu m.

(c) Constructing a perfusion opening 103 of the titanium alloy porous interbody fusion cage, designing a cylindrical perfusion opening 103 in each of four directions of a compact bearing periphery 102 of the titanium alloy porous interbody fusion cage, wherein the radius of the perfusion opening 103 is 3mm, the length of the perfusion opening is 20mm, and the inner part of the perfusion opening is connected with a gradient porous structure 101.

(d) And slicing the model, taking medical-grade titanium alloy powder as a raw material, and preparing the titanium alloy porous interbody fusion cage by using a laser selective melting 3D printing technology.

(2) Preparing sodium alginate hydrogel of composite nano hydroxyapatite;

(a) 3g of sodium alginate powder is dissolved in 100mL of up water by a magnetic stirring device to prepare a 3 wt% sodium alginate aqueous solution.

(b) And (3) melting 500mg of nano-hydroxyapatite in the 100mL of sodium alginate aqueous solution by using a mixing and defoaming device to prepare the composite sodium alginate hydrogel, wherein the concentration of the nano-hydroxyapatite is 5 mg/mL.

3. Preparing a titanium alloy porous interbody fusion cage carrying the composite sodium alginate hydrogel;

(a) using a syringe to suck enough sodium alginate hydrogel compounded with nano hydroxyapatite to inject the sodium alginate hydrogel into the porous structure 101 of the titanium alloy porous interbody fusion cage through 4 perfusion openings 103.

(b) Placing the titanium alloy porous interbody fusion cage into 5 wt% CaCl₂Crosslinking in the solution for 12 hours to make the composite hydrogel gel.

(c) And (3) putting the titanium alloy porous interbody fusion cage carrying the composite hydrogel for gelling into a freeze dryer, and carrying out vacuum freeze-drying at-70 ℃ for 24 hours to remove water in the hydrogel.

The 3D printing titanium alloy porous interbody fusion cage with the nano-hydroxyapatite carried inside, which is prepared through the steps, has a porous structure 101 with the pore diameter gradually reduced from the inside of the titanium alloy porous interbody fusion cage to the outside, the porosity is 59% -93%, the pore diameter is 550-880 mu m, and the variation gradient of the pore diameter is 30 mu m; there are 4 perfusion openings 103 of the same shape, with a radius of 3mm and a length of 20mm, internally connected to the gradient porous structure 101. The titanium alloy porous interbody fusion cage is loaded with sodium alginate hydrogel with composite concentration of 5mg/mL nano hydroxyapatite, and the sodium alginate hydrogel is filled in the porous structure 101 of the titanium alloy porous interbody fusion cage after being crosslinked and freeze-dried.

Example 2

In designing the macroscopic appearance of the titanium alloy porous interbody cage, a large area bone graft region 104 is reserved, as shown in fig. 6. According to the method of the embodiment 1, firstly, a 3D printed titanium alloy porous interbody fusion cage is prepared, then, preparation and carrying of sodium alginate hydrogel of composite nano hydroxyapatite are carried out, and the selection of other parameters and the preparation process are the same as those of the embodiment 1, except that the macroscopic appearance structure of the fusion cage is adjusted in the embodiment, a large-area bone grafting area 104 which penetrates up and down is constructed in the center of the titanium alloy porous interbody fusion cage, the shape of the bone grafting area 104 is the same as the outline of the titanium alloy porous interbody fusion cage, the size of the bone grafting area is half of the outline, the volume of the porous structure 101 is reduced, and the surface area of composite hydrogel infiltration is increased, as shown in fig. 6. In particular, in this embodiment it is necessary to reduce the length of the cylindrical pouring opening 103 slightly in order to avoid leakage from the middle during injection, with a radius of 3mm and a length of 12 mm. Compared with the embodiment 1, the titanium alloy porous interbody fusion cage carrying the nano-hydroxyapatite is finally obtained, the carrying amount is reduced by 26.4%, and the infiltration surface area is increased by 17.3%.

Example 3

According to the method of the embodiment 1, the titanium alloy porous interbody fusion cage carrying the nano hydroxyapatite is prepared, and the selection of other parameters and the preparation process are the same as those of the embodiment 1, except that when the macroscopic appearance structure of the titanium alloy porous interbody fusion cage is constructed, the proportion of the dense force-bearing periphery 102 is increased and the proportion of the central porous structure 101 is reduced when the total volume of the titanium alloy porous interbody fusion cage is kept unchanged, as shown in fig. 7. Compared with the embodiment 1, the mechanical property of the finally obtained titanium alloy porous interbody fusion cage is changed, the compression strength is increased by 13.7%, and the elastic modulus is increased by 12.8%. However, the loading amount of the nano-hydroxyapatite is reduced by 15.3% due to the reduction of the porous structure 101.

Example 4

According to the method of the embodiment 1, the titanium alloy porous interbody fusion cage carrying the nano-hydroxyapatite is prepared, and the selection of other parameters and the preparation process are the same as those of the embodiment 1, except that when the macroscopic appearance structure of the titanium alloy porous interbody fusion cage is constructed, the proportion of the dense force-bearing periphery 102 is replaced by the porous structure 101 when the total volume of the titanium alloy porous interbody fusion cage is kept unchanged, so that the titanium alloy porous interbody fusion cage is completely composed of the gradient porous structure 101, as shown in fig. 8. Compared with the example 1, the mechanical property of the finally obtained titanium alloy porous interbody fusion cage is changed, the compression strength is reduced by 36.6%, and the elastic modulus is reduced by 39.3%. However, as the porous structure 101 is increased, the loading amount of the nano hydroxyapatite is increased by 29.1%.

Example 5

The titanium alloy porous interbody cage carrying nano-hydroxyapatite was prepared according to the method of example 1, and the remaining parameter selection and preparation process were the same as those of example 1, except that the number of the 4 cylindrical perfusion openings 103 of the titanium alloy porous interbody cage was reduced to 1 when the perfusion openings 103 of the titanium alloy porous interbody cage were constructed, as shown in fig. 9. The content of the composite hydrogel carried by the finally obtained titanium alloy porous interbody fusion cage is not changed greatly, but the carrying difficulty is increased and the operation time is increased due to the lengthened hydrogel flow path.

Example 6

The titanium alloy porous interbody fusion cage carrying nano-hydroxyapatite was prepared according to the method of example 1, and the selection of the remaining parameters and the preparation process were the same as those of example 1, except that the concentration of nano-hydroxyapatite was reduced to 1mg/mL when preparing the composite hydrogel. The finally obtained composite hydrogel has reduced viscosity and good fluidity. The finally obtained titanium alloy porous interbody fusion cage with the composite nano hydroxyapatite can reduce the active regeneration fusion capability of the induced bone and reduce the bone fusion amount in the same time.

Example 7

According to the method of the embodiment 1, the titanium alloy porous interbody fusion cage carrying the active ingredient or the drug having the function of actively inducing the regeneration of the bone tissue is prepared, and the selection of the other parameters and the preparation process are the same as the embodiment 1, except that the nano-hydroxyapatite is changed into the bone morphogenetic protein 2 with the concentration of 500 mug/mL when the composite hydrogel is prepared. The finally obtained composite hydrogel has reduced viscosity and good fluidity. The finally obtained titanium alloy porous interbody fusion cage of the composite bone morphogenetic protein 2 induces the reduction of the active bone regeneration fusion capacity, and the bone fusion amount is reduced in the same time.

Example 8

According to the method of the embodiment 1, the gradient porous interbody fusion cage carrying the active ingredient or the drug with the function of actively inducing the regeneration of the bone tissue is prepared, and the selection of other parameters and the preparation process are the same as the embodiment 1, except that the nano-hydroxyapatite is changed into the zoledronic acid with the concentration of 100 mug/mL when the composite hydrogel is prepared. The finally obtained composite hydrogel has reduced viscosity and good fluidity. The finally obtained titanium alloy porous interbody fusion cage compounded with zoledronic acid has reduced active bone regeneration fusion capacity and reduced bone fusion amount in the same time.

Comparative example 1

The gradient porous structure 101 is replaced with a uniform porous structure. According to the method of the embodiment 1, the titanium alloy porous interbody fusion cage is prepared by 3D printing, and then the sodium alginate hydrogel of the composite nano hydroxyapatite is prepared and carried, so that the spine repair system for actively inducing bone tissue regeneration fusion is constructed. The selection of other parameters and the preparation process are the same as those in example 1, except that in this example, the macroscopic porous structure 101 of the titanium alloy porous interbody fusion cage is adjusted, the gradient porous structure 101 is replaced with a uniform and equal-sized porous structure, the pore diameter is designed to be 710 μm, and the porosity is designed to be 76.3%. In this comparative example, since the porous structure 101 has no variation gradient and the internal and external permeability are the same, the slow release effect of the titanium alloy porous interbody fusion cage on the carried nano-hydroxyapatite is reduced, and the release completion time is reduced by 66.4%.

Comparative example 2

The perfusion opening 103 is not designed for the fusion cage. According to the method of the embodiment 1, the titanium alloy porous interbody fusion cage is prepared by 3D printing, and then the sodium alginate hydrogel of the composite nano hydroxyapatite is prepared and carried, so that the spine repair system for actively inducing bone tissue regeneration fusion is constructed. The remaining parameter selection and preparation process are the same as those in example 1, except that the perfusion opening 103 is not designed when the model of the titanium alloy porous interbody fusion cage is constructed. In this comparative example, since the sodium alginate hydrogel compounded with nano hydroxyapatite is difficult to directly permeate into the interior from the pores with relatively smaller surface pore size, the method of vacuum pumping is adopted for perfusion, but the loading amount is still not ideal. The finally obtained titanium alloy porous interbody fusion cage reduces the loading amount of nano hydroxyapatite by 41.2 percent.

Comparative example 3

Active ingredients or medicaments with the function of actively inducing the regeneration of bone tissues are not carried. The preparation of the titanium alloy porous interbody cage by 3D printing was performed according to the method of example 1. The selection of other parameters and the preparation process are the same as those in example 1, except that the titanium alloy porous interbody fusion cage is not loaded with active ingredients or drugs having the function of actively inducing bone tissue regeneration, such as nano hydroxyapatite. In this comparative example, since the titanium alloy itself does not have osteoinductive capacity and cannot induce new bone formation, the bonding strength between the obtained titanium alloy porous intervertebral cage and the upper and lower vertebral bodies is low, the bone fusion rate is greatly reduced, and the spinal column repair effect is not good.

Therefore, the spine repair system for actively inducing bone tissue regeneration fusion and the manufacturing method thereof are disclosed, and the repair system is a 3D printing customized perfusion type titanium alloy porous interbody fusion cage internally carrying active ingredients or medicines with the function of actively inducing bone tissue regeneration. The invention designs a titanium alloy porous interbody fusion cage model with a pourable opening 103 and a macroscopic porous structure 101 through parametric modeling, shapes the model by using a laser selective melting 3D printing technology, and then loads an active ingredient or a medicament into the interior of the fusion cage through the pourable opening 103. In the invention, the structure customization, in-situ slow release capability and function diversification design of the repair system can be realized by designing the aperture and porosity of the gradient porous structure 101, the shape, size and position of the perfusion opening 103, and regulating and controlling the parameters such as the type, content and proportion of the loaded active ingredients or medicines, the bioactivity function of the repair system is obviously improved, the repair system has the function of actively inducing bone tissue regeneration and fusion, and guiding new bones to grow into defect parts, so that firm combination and fusion unification between the intervertebral fusion cage and vertebral bodies are formed, and perfect repair of the vertebral column is realized.

In the description of the present invention, it is to be noted that, unless otherwise specified, "a plurality" means two or more; the terms "upper", "lower", "left", "right", "inner", "outer", "front", "rear", "head", "tail", and the like, indicate orientations or positional relationships based on the orientations or positional relationships shown in the drawings, are only for convenience in describing and simplifying the description, and do not indicate or imply that the device or element referred to must have a particular orientation, be constructed in a particular orientation, and be operated, and thus, should not be construed as limiting the invention. Furthermore, the terms "first," "second," "third," and the like are used for descriptive purposes only and are not to be construed as indicating or implying relative importance.

In the description of the present invention, it should also be noted that, unless otherwise explicitly specified or limited, the terms "mounted," "connected," and "connected" are to be construed broadly, e.g., as meaning either a fixed connection, a removable connection, or an integral connection; can be mechanically or electrically connected; may be directly connected or indirectly connected through an intermediate. The specific meaning of the above terms in the present invention can be understood as appropriate to those of ordinary skill in the art.

The above description is only for the specific embodiments of the present invention, but the scope of the present invention is not limited thereto, and any person skilled in the art can easily conceive of the changes or substitutions within the technical scope of the present invention, and all the changes or substitutions should be covered within the scope of the present invention. Therefore, the protection scope of the present invention shall be subject to the protection scope of the appended claims.

Claims (10)

1. The spinal repair system is characterized by comprising a titanium alloy porous interbody fusion cage and an active ingredient or medicament with the biological function of actively inducing bone tissue regeneration fusion, wherein the titanium alloy porous interbody fusion cage is provided with a porous structure (101), and the porous structure (101) is used for carrying the active ingredient or medicament.

2. The active induction bone tissue regeneration fusion spinal column repair system of claim 1, characterized in that the titanium alloy porous interbody cage further comprises a dense force-bearing periphery (102), the dense force-bearing periphery (102) being disposed around the porous structure (101).

3. The system for actively inducing bone tissue regeneration fusion spinal repair according to claim 2, characterized in that the titanium alloy porous intervertebral cage further comprises at least one perfusion opening (103), wherein the perfusion opening (103) is arranged on the dense force-bearing periphery (102), and the perfusion opening (103) penetrates through the dense force-bearing periphery (102) and is connected with the porous structure (101).

4. The system for actively inducing bone tissue regeneration fusion spinal repair according to one of claims 1 to 3, characterized in that the porous structure (101) is a gradient porous structure.

5. The system for actively inducing bone tissue regeneration fusion spinal repair according to claim 4, characterized in that the pore size of the porous structure (101) is gradually reduced from the inside of the titanium alloy porous interbody cage outwards.

6. The active bone tissue regeneration fusion spinal repair system according to claim 5, characterized in that the porosity of the porous structure (101) is 59-93%, and the pore diameter is 550-880 μm; the gradient of the pore diameter is 30 μm, and the gradient of the pore diameter is increased from the inside of the titanium alloy porous interbody fusion cage to the outside.

7. The active bone tissue regeneration fusion spinal repair system according to one of claims 1 to 3, wherein the active ingredient or drug having the biological function of actively inducing bone tissue regeneration fusion is nano-hydroxyapatite, bone morphogenetic protein 2 or zoledronic acid.

8. A method for manufacturing the spinal repair system for actively inducing bone tissue regeneration fusion according to any one of claims 1 to 7, comprising the following steps:

reconstructing upper and lower vertebral body models of a part to be repaired according to the CT data;

analyzing parameters of the upper and lower vertebral body models of the part to be repaired, and constructing a macroscopic appearance of the titanium alloy porous interbody fusion cage;

analyzing the stress of the titanium alloy porous interbody fusion cage, and constructing a porous structure (101) of the titanium alloy porous interbody fusion cage;

constructing a perfusion opening (103) of the titanium alloy porous interbody cage;

preparing the titanium alloy porous interbody fusion cage by using a selective laser melting 3D printing technology;

active ingredients or medicines with the biological function of actively inducing bone tissue regeneration and fusion are loaded into the porous structure (101) of the titanium alloy porous interbody fusion cage through the perfusion opening (103);

freeze-drying the composite perfusion slurry, and storing the active ingredient or the medicine.

9. The method for manufacturing the spinal column repair system with actively induced bone tissue regeneration fusion according to claim 8, wherein the method for loading the active ingredient or drug with the biological function of actively induced bone tissue regeneration fusion into the titanium alloy porous intervertebral cage through the perfusion opening (103) comprises the following steps:

mixing 3-5 wt% sodium alginate water solution with active component or medicine;

after being uniformly mixed, a sufficient amount of the mixture is sucked through the perfusion opening (103) by using a syringe and is injected into the interior of the titanium alloy porous interbody fusion cage;

placing the titanium alloy porous interbody fusion cage into 5-10 wt% of CaCl₂And (3) crosslinking for 3-12 hours in the solution to enable the sodium alginate to gel.

10. The method for manufacturing a spinal repair system with actively induced bone tissue regeneration fusion according to claim 8, wherein the method for preserving active ingredients or drugs comprises:

and (3) putting the titanium alloy porous interbody fusion cage after the sodium alginate is gelatinized into the gel into a freeze dryer, and freeze-drying for 12-24 hours in vacuum to remove the water in the hydrogel.

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