CN106823007A - Bone renovating material and preparation method thereof - Google Patents

The invention provides a kind of bone renovating material and preparation method thereof.The bone renovating material is loose structure, and bone renovating material includes β TGFs, hydroxyapatite, β tricalcium phosphates and collagen.Propagation, differentiation of the loose structure beneficial to osteocyte.Include hydroxyapatite and β tricalcium phosphates simultaneously, overcome the shortcoming that hydroxyapatite is excessively stablized, the degraded of β tricalcium phosphates is too fast, balance the degradation speed of material, its matching skeleton preferably is repaired speed.Collagen can promote cell migration, stick, breaks up and adjust cell growth.β TGFs can promote propagation and the differentiation of periosteum mesenchymal cell, promote the propagation of Gegenbaur's cell, be played a very important role during metabolism of bone tissue.In a word, the bone renovating material that the present invention is provided has had any of the above advantage concurrently, can match the reparation speed of skeleton, meets the Bone Defect Repari demand at defect of human body bone.

Bone renovating material and preparation method thereof

Technical field

The present invention relates to technical field of biological materials, in particular to a kind of bone renovating material and preparation method thereof.

Background technology

China just steps into aging society, increases rheological properties and changes and with the disease for occurring substantial amounts of Cranial defect will be caused to rebuild Demand, including bone- xenograft, homogeneous allogenic bone, synthetic material etc., above material all exists certain traditional bone grafting timbering material Limitation：Homogeneous allogenic bone limited source；There is source and price problem in bone- xenograft, while spreading disease, cause host to exempt from Epidemic disease rejection equivalent risk；The aspects such as porosity, hole traffic, the pore size of synthetic material are different from human body cancellous bone, right Cell stick and breed it is unfavorable, it is more difficult to promote the differentiation and maturation of Gegenbaur's cell.

Hydroxyapatite (HA) is the main component of forging bone, is also the main component of inanimate matter in body bone tissue, with Tissue has good biocompatibility, but HA degradation in vivo is slower, and bone tissue is difficult generation in a short time.β-tricresyl phosphate Calcium (β-TCP) not only has good biocompatibility, and with good biological degradability, its catabolite Ca²⁺、PO₄ ^3- Plasma can enter living body fluids, for is formationed of new bone provides the beneficial element such as Ca, P for enriching, promote the formation of new bone, but β- TCP degradation speeds in vivo are slightly fast, mismatched with new bone growth speed.Additionally, the big multipair human body of existing bone renovating material The facilitation of the Bone Defect Repari at Cranial defect is smaller.Accordingly, it would be desirable to further being studied for bone renovating material, to meet Bone Defect Repari at defect of human body bone needs.

The content of the invention

It is a primary object of the present invention to provide a kind of bone renovating material and preparation method thereof, to solve bone in the prior art Repair materials are unsatisfactory for the Bone Defect Repari needs of problems at defect of human body bone.

To achieve these goals, according to an aspect of the invention, there is provided a kind of bone renovating material, it is porous knot Structure, and bone renovating material includes β TGFs, hydroxyapatite, bata-tricalcium phosphate and collagen.

Further, collagen is I-type collagen.

Further, collagen is using the I-type collagen after cross-linking agents.

Further, crosslinking agent is glutamine transaminage and/or Geniposide.

Further, the weight ratio of hydroxyapatite and bata-tricalcium phosphate is 40~80:20~60；Preferably, β conversions life The content of the factor long is relative to 1~30ng/g of hydroxyapatite and bata-tricalcium phosphate gross weight；Preferably, the content of collagen It is 5~25% relative to hydroxyapatite and bata-tricalcium phosphate gross weight.

According to another aspect of the present invention, there is provided a kind of preparation method of above-mentioned bone renovating material, it includes following Step：Take mammal cancellous bone enter successively water-filling boil, phosphoric acid solution immersion, boiling, drying, obtain pre-process cancellous bone； Pretreatment cancellous bone is placed in treatment is modified in dibastic sodium phosphate solution or disodium phosphate soln, obtain modified spongiosa Bone；By the calcining of modified cancellous bone, hydroxyapatite-bata-tricalcium phosphate composite is obtained；And by hydroxyapatite-β-phosphoric acid After DFP composite carries out pH regulations with the mixture of collagen solution, to β TGF solution is added in mixture, so After carry out first time ice bath treatment, dry, obtain bone renovating material.

Further, after carrying out the step of first time ice bath is processed and before drying, also including to addition β conversion lifes The step of crosslinking agent being added in mixture after factor solutions long；It is preferred that the consumption of crosslinking agent is collagen weight in collagen solution 0.001~0.1%.

Further, in the step of modification, the mass concentration of dibastic sodium phosphate solution is 0.5~2.5%, phosphoric acid hydrogen two The mass concentration of sodium solution is 0.5~2.5%, and process time is 1.5~2.5h.

Further, the step of obtaining the mixture of hydroxyapatite-bata-tricalcium phosphate composite and collagen solution is wrapped Include：Collagen is mixed with acetic acid aqueous solution, collagen solution is obtained；By hydroxyapatite-bata-tricalcium phosphate composite and collagen Solution mixes, and obtains mixture.

Further, after the step of adding crosslinking agent, the step of also treatment including carrying out second ice bath；Preferably, During mixture is carried out the step of pH is adjusted, pH value to 7~8 is reconciled；Preferably, in the treatment of first time ice bath, mixing speed is 500~5000r/min, process time is 1~2h；Preferably, in second ice bath treatment, mixing speed is 500~5000r/ Min, process time is 1~2h；Preferably, after carrying out the step of second ice bath is processed and before drying, at 15~25 DEG C At a temperature of stand 3~5 hours.

Apply the technical scheme of the present invention, bone renovating material is loose structure, and bone renovating material include β convert growth because Son, hydroxyapatite, bata-tricalcium phosphate and collagen.Propagation, differentiation of the loose structure beneficial to osteocyte.Include hydroxy-apatite simultaneously Stone and bata-tricalcium phosphate, overcome the shortcoming that hydroxyapatite is excessively stablized, bata-tricalcium phosphate degraded is too fast, balance material Degradation speed, makes its matching skeleton preferably repair speed.Collagen has many advantages：Nontoxic, low antigenicity is good Biocompatibility, biodegradability and Bioabsorbable, can promote cell migration, stick, break up and adjust cell growth. β TGFs (TGF-β) are the multi-functional polypeptide proteins of family, are widely present in body normal tissue cell and conversion In cell, content highest in bone tissue and blood platelet.TGF-β has promotion cell propagation, regulation cell differentiation, promotion extracellular Matrix synthesizes and regulation immunity of organism effect.TGF-β can promote propagation and the differentiation of periosteum mesenchymal cell, promote skeletonization (soft Bone) cell propagation, stimulate collagen, bony union element and osteopontin synthesis.Meanwhile, TGF-β can suppress the life of osteoclast Into and mature osteoclast activity, so as to suppress bone resorption.As can be seen here, TGF-β is during metabolism of bone tissue Play a very important role.In a word, the bone renovating material that the present invention is provided has had any of the above advantage concurrently, can match human body The reparation speed of bone, meets the Bone Defect Repari demand at defect of human body bone.

Brief description of the drawings

The Figure of description for constituting the part of the application is used for providing a further understanding of the present invention, of the invention to show Meaning property and its illustrates, for explaining the present invention, not constitute inappropriate limitation of the present invention embodiment.In the accompanying drawings：

Fig. 1 shows the scanning electricity of the hydroxyapatite-bata-tricalcium phosphate composite in embodiments in accordance with the present invention 1 Mirror figure；And

Fig. 2 shows the scanning electron microscope (SEM) photograph of the bone renovating material according to an embodiment of the present in 1.

Specific embodiment

It should be noted that in the case where not conflicting, the feature in embodiment and embodiment in the application can phase Mutually combination.Describe the present invention in detail below with reference to the accompanying drawings and in conjunction with the embodiments.

The application is described in further detail below in conjunction with specific embodiment, these embodiments are it is not intended that limit this Apply for scope required for protection.

As described by background section, the Bone Defect Repari that existing bone renovating material is unsatisfactory at defect of human body bone is needed Ask.

In order to solve this problem, the invention provides a kind of bone renovating material, it is loose structure, and bone renovating material Including β TGFs, hydroxyapatite, bata-tricalcium phosphate and collagen.Propagation, differentiation of the loose structure beneficial to osteocyte. Simultaneously include hydroxyapatite and bata-tricalcium phosphate, overcome hydroxyapatite excessively stablize, bata-tricalcium phosphate degraded it is too fast Shortcoming, balances the degradation speed of material, its matching skeleton preferably is repaired speed.Collagen has many advantages：Nothing Poison, low antigenicity, good biocompatibility, biodegradability and Bioabsorbable, can promote cell migration, stick, Differentiation and regulation cell growth.β TGFs (TGF-β) are the multi-functional polypeptide proteins of family, are widely present in body In normal tissue cell and transformed cells, content highest in bone tissue and blood platelet.TGF-β has promotion cell propagation, adjusts Ganglion cell's differentiation, the synthesis of promotion extracellular matrix and regulation immunity of organism effect.TGF-β can promote the increasing of periosteum mesenchymal cell Grow and break up, promote the propagation of skeletonization (cartilage) cell, stimulate the synthesis of collagen, bony union element and osteopontin.Meanwhile, TGF- β can suppress the generation of osteoclast and the activity of mature osteoclast, so as to suppress bone resorption.As can be seen here, TGF-β Played a very important role during metabolism of bone tissue.In a word, the bone renovating material that the present invention is provided has had concurrently each above Advantage is planted, the reparation speed of skeleton can be matched, meet the Bone Defect Repari demand at defect of human body bone.

In a preferred embodiment, collagen is I-type collagen.I-type collagen has biofacies higher Capacitive, as the collagen in bone renovating material, can further promote the reparation of skeleton.

In a preferred embodiment, collagen is using the I-type collagen after cross-linking agents.Non-crosslinked I-type collagen is linear structure, after cross-linking, can significantly improve its stability, not readily dissolves dispersion, and being more convenient should With.

Above-mentioned crosslinking agent can be using the crosslinking agent of collagen commonly used in the art, such as glutaraldehyde, oneself different two cyanic acid Ester, carbodiimides, nitrine diphenylphosphine etc..In a preferred embodiment, crosslinking agent be glutamine transaminage and/ Geniposide.Glutamine transaminage and/or Geniposide as collagen cross-linking agent, except with preferable cross-linking properties, energy Enough improve outside the stability of collagen, while having more preferable biological nature, apply more suitable in bone renovating material. Especially glutamine transaminage, preferably as above-mentioned crosslinking agent.

In a preferred embodiment, the weight ratio of hydroxyapatite and bata-tricalcium phosphate is 40~80:20~60； Preferably, the content of β TGFs is relative to 1~30ng/g of hydroxyapatite and bata-tricalcium phosphate gross weight；It is excellent Selection of land, the content of collagen is relative to hydroxyapatite and bata-tricalcium phosphate gross weight 5~25%.By the use between each composition Magnitude relation is controlled within the above range, and the performance of bone renovating material each side is more balanced, and can be played into one between each composition The positive cooperative effect in step ground, has more preferably facilitation for the reparation of skeleton.

In addition, according to another aspect of the present invention, additionally providing a kind of preparation method of above-mentioned bone renovating material, it includes Following steps：Take mammal cancellous bone enter successively water-filling boil, phosphoric acid solution immersion, boiling, drying, obtain pre-process spongiosa Bone；Pretreatment cancellous bone is placed in treatment is modified in dibastic sodium phosphate solution or disodium phosphate soln, obtain modified pine Matter bone；By the calcining of modified cancellous bone, hydroxyapatite-bata-tricalcium phosphate composite is obtained；By hydroxyapatite-β-tricresyl phosphate After calcium composite carries out pH regulations with the mixture of collagen solution, to β TGF solution is added in mixture, then First time ice bath treatment is carried out, is dried, obtain bone renovating material.

In above-mentioned process step, take after mammal cancellous bone carries out series of processes, pretreatment cancellous bone is placed in phosphoric acid Treatment is modified in hydrogen sodium solution or disodium phosphate soln, after the modified cancellous bone for obtaining is through high-temperature calcination, that is, is formed Hydroxyapatite-bata-tricalcium phosphate composite.Again by hydroxyapatite-bata-tricalcium phosphate composite and collagen solution After mixture carries out pH regulations, the is carried out to β TGF solution, the balance solution that then will be obtained is added in mixture One time ice bath is processed, dried, you can obtain including β TGFs, hydroxyapatite, bata-tricalcium phosphate and collagen simultaneously Bone renovating material.The cancellous bone of specific mammal can be its spine, femur etc..

The porosity of the bone renovating material, hole traffic, pore size and human body cancellous bone are basically identical, beneficial to osteocyte Propagation, differentiation.Include hydroxyapatite and bata-tricalcium phosphate simultaneously, overcome hydroxyapatite excessively stable, β-tricresyl phosphate The too fast shortcoming of calcium degraded, balances the degradation speed of material, its matching skeleton preferably is repaired speed.Collagen has Many advantages：It is nontoxic, low antigenicity, good biocompatibility, biodegradability and Bioabsorbable can promote cell Migrate, stick, break up and adjust cell growth.β TGFs (TGF-β) are the multi-functional polypeptide proteins of family, extensively It is present in body normal tissue cell and transformed cells, content highest in bone tissue and blood platelet.TGF-β has promotion thin Born of the same parents' propagation, regulation cell differentiation, the synthesis of promotion extracellular matrix and regulation immunity of organism effect.TGF-β fills between can promoting periosteum The propagation of cell plastid and differentiation, promote the propagation of skeletonization (cartilage) cell, stimulate the conjunction of collagen, bony union element and osteopontin Into.Meanwhile, TGF-β can suppress the generation of osteoclast and the activity of mature osteoclast, so as to suppress bone resorption.By This is visible, and TGF-β is played a very important role during metabolism of bone tissue.In a word, the bone renovating material that the present invention is provided Have any of the above advantage concurrently, the reparation speed of skeleton can have been matched, meet the Bone Defect Repari demand at defect of human body bone.

In a preferred embodiment, after carrying out the step of first time ice bath is processed and before drying, also wrap The step of including to crosslinking agent is added in the mixture after the treatment of first time ice bath.Crosslinking agent is added, collagen egg can be significantly improved White stability, makes it have certain viscosity, not readily dissolves dispersion, is more convenient application.

In a preferred embodiment, in the step of modification, the mass concentration of dibastic sodium phosphate solution for 0.5~ 2.5%, the mass concentration of disodium phosphate soln is 0.5~2.5%, and process time is 1.5~2.5h.Modified treatment, can So that modified cancellous bone is presented hydroxyapatite-bata-tricalcium phosphate two phase structure after calcining.Meanwhile, by adjusting dibastic sodium phosphate The concentration and process time of solution and disodium phosphate soln, can adjust the ratio between two-phase.And the present invention preferably will be dense Degree and process time control within the above range, can make the weight ratio of hydroxyapatite and bata-tricalcium phosphate reach 40~80: 20~60, and then can further balance Bone Defect Repari speed.

In a preferred embodiment, hydroxyapatite-bata-tricalcium phosphate composite is obtained with collagen solution The step of mixture, includes：Collagen is mixed with acetic acid aqueous solution, collagen solution is obtained；By hydroxyapatite-bata-tricalcium phosphate Composite mixes with collagen solution, obtains mixture.

In a preferred embodiment, after the step of adding crosslinking agent, also including carrying out second ice bath treatment The step of；Preferably, in second ice bath treatment, mixing speed is 500~5000r/min, and process time is 1~2h.In this way, Collagen can be made more fully to be crosslinked using second ice bath treatment, stability is more preferably.Preferably, first time ice bath treatment In, mixing speed is 500~5000r/min, and process time is 1~2h.So, collagen and hydroxyapatite-β-phosphoric acid Can preferably disperse between DFP composite.Preferably, after carrying out the step of second ice bath is processed and before drying, 3~5 hours are stood at a temperature of 15~25 DEG C.The process is ageing process, can disperse each component more uniform.Preferably, During mixture is carried out the step of pH is adjusted, pH value to 7~8 is reconciled.PH value is reconciled to 7~8, is more suitable for human body acid-base environment. Preferably, after standing 3~5 hours at a temperature of 15~25 DEG C, after it is transferred in rustless steel container, -10~-30 DEG C are placed into Lower freezing processing 24 hours, freeze-drying process at being then transferred to -80 DEG C obtains bone renovating material

When collagen solution is configured, those skilled in the art can select its concentration and use according to final with magnitude relation Amount.Preferably, the I-type collagen extracted from ox heel string is added in the acetic acid aqueous solution that mass fraction is 0.5% and is matched somebody with somebody Collagen solution is set to, the content of collagen accounts for the 5% of the liquid quality fraction.Added with every 10 milliliters of collagen acetic acid solutions The ratio of 2~5g hydroxyapatites-bata-tricalcium phosphate composite is to addition hydroxyapatite-tricresyl phosphate in collagen acetic acid solution Calcium composite, is well mixed, and adjust pH value to 7~8.Then admixture concentration is the β conversion lifes of 1~30ng/ml thereto Factor solutions long, carry out first time ice bath treatment in the process.Preferably, the β TGFs solution of use can be With the solution that physiological saline is configured as solvent.

It is above-mentioned take mammal spine, the cancellous bone of femur enter successively water-filling boil, phosphoric acid solution immersion, boiling, drying, obtain To pretreatment cancellous bone.The concrete technology of the step can be adjusted.Specifically, actual behaviour can be carried out according to following condition Make：

Step one, take mammal spine, the cancellous bone portion of femur be cut into small pieces after water boil, dry；

Step 2, dried cancellous bone is soaked with phosphoric acid solution；

Step 3, phosphoric acid solution is soaked after cancellous bone be positioned over boiling in pressure cooker, by after boiling cancellous bone use Deionized water rinse for several times, to pH value be 7 when dry；

The cancellous bone of mammal spine, femur carries out stripping and slicing, water are boiled, dry method is by spine, femoral component Cancellous bone be cut into 1cm³Fritter, is put into after a pot reclaimed water boils 3~4 hours, is rinsed for several times with clear water, is placed in drying box, 120~ 140 DEG C of 6~8h of drying.Phosphoric acid solution used, its mass concentration is 0.5~5%, and soak time is 0.5~5 hour.Spongiosa Bone boiling in pressure cooker, temperature is 125 DEG C, and the time is 2~4 hours.

In above-mentioned calcination process, after modified cancellous bone high temperature furnace preferably is warmed up into 300~400 DEG C, insulation 0.5~2 Hour；After being continuously heating to 500~600 DEG C, 0.5~2h is incubated；After being continuously heating to 700~800 DEG C, 0.5~2h is incubated；After Continue after being warming up to 900~1000 DEG C, be incubated 0.5~2h；After being continuously heating to 1000~1100 DEG C, 0.5~2 hour is incubated.Should Under calcination condition, the material pore structure of formation is more stablized.

Beneficial effects of the present invention are further illustrated by the following examples：

Embodiment 1

Step 1, the spine cancellous bone for choosing healthy, fresh 9 monthly ages Tibetan yak, by spine, the spongiosa of femoral component Bone is cut into 1cm³Fritter, is put into after a pot reclaimed water boils 4 hours, is rinsed for several times with clear water, is placed in drying box, 120~140 DEG C of dryings 6~8h.Dried cancellous bone is soaked in phosphoric acid solution, phosphoric acid solution mass concentration is 3%, soak time is 3 hours. Cancellous bone boiling in pressure cooker, temperature is 125 DEG C, and the time is 3 hours.Dry, obtain pre-processing cancellous bone；

Step 2,2h will be soaked during pretreatment cancellous bone adds to the disodium hydrogen phosphate aqueous solution that mass concentration is 2%, obtained Modified cancellous bone；

Step 3, by the calcining of modified cancellous bone, after modified cancellous bone high temperature furnace specifically is warmed up into 400 DEG C, insulation is 0.5 small When；After being continuously heating to 500 DEG C, 2h is incubated；After being continuously heating to 800 DEG C, 0.5h is incubated；After being continuously heating to 1000 DEG C, protect Warm 0.5h；After being continuously heating to 1100 DEG C, 0.5 hour is incubated.(SEM schemes to obtain hydroxyapatite-bata-tricalcium phosphate composite See Fig. 1), the continuous poriferous structure that it remains original natural bone as can be seen from Fig. 1, with very big internal surface area, is conducive to The implantation and adhesion of cell, and cytotrophy composition infiltration and the discharge of products of cellular metabolism；

By hydroxyapatite-bata-tricalcium phosphate composite crushing and screening, the particle that particle diameter is 0.1~2mm is chosen standby；

Step 4, by from ox heel string extract I-type collagen be added in the acetic acid solution that mass fraction is 0.5% Collagen acetic acid solution is configured to, the content of collagen accounts for the 5% of the liquid quality fraction；

To add the ratio of 5g hydroxyapatites-bata-tricalcium phosphate composite in every 10 milliliters of collagen acetic acid solutions to glue Hydroxyapatite-bata-tricalcium phosphate composite is added in ortho-acetic acid solution, is well mixed, and adjust pH value to 7.Then to it The normal saline solution of the β TGFs of middle addition 1ng/ml.In the process, stirred with 3000 turns per minute under ice bath Mix, the time is 1.5 hours.It is subsequently adding crosslinking agent (dosage of crosslinking agent is the 0.08% of collagen) glutamine transaminage, ice bath With 3000 turns per minute stirrings, the time is 1.5 hours, when then standing 3 at 25 DEG C for lower continuation.Above-mentioned solution is transferred to not After in rust steel container, freezing processing 24 hours at being placed into -30 DEG C, freeze-drying process at being then transferred to -80 DEG C.Bone is obtained to repair Multiple material (SEM figures are shown in Fig. 2).As shown in Figure 2, the bone renovating material is loose structure.

In above-mentioned bone renovating material, the weight ratio of hydroxyapatite and bata-tricalcium phosphate is 6:4, β TGFs Content is relative to the 1ng/g of hydroxyapatite and bata-tricalcium phosphate gross weight；The content of collagen is relative to hydroxyapatite With the 9.1% of bata-tricalcium phosphate gross weight.

Embodiment 2

Preparation technology is same as Example 1, and difference is：

Will be during pretreatment cancellous bone add to the disodium hydrogen phosphate aqueous solution that mass concentration is 0.5% in step 2, immersion 2.5h, obtains modified cancellous bone；

During mixture is carried out the step of pH is adjusted in step 4, pH value to 8 is reconciled；In the treatment of first time ice bath, stirring speed It is 5000r/min to spend, and process time is 1h；In second ice bath treatment, mixing speed is 5000r/min, and process time is 1h； After the step of second ice bath is processed and before drying, 5 hours are stood at a temperature of 15 DEG C.Change collagen acetic acid solution and β The addition of TGF.Dosage of crosslinking agent is the 0.1% of collagen.

In the bone renovating material for finally giving, the weight ratio of hydroxyapatite and bata-tricalcium phosphate is 8:2, β conversion growths The content of the factor is relative to the 30ng/g of hydroxyapatite and bata-tricalcium phosphate gross weight；The content of collagen is relative to hydroxyl The 5% of apatite and bata-tricalcium phosphate gross weight.

Embodiment 3

Preparation technology is same as Example 1, and difference is：

In step 2 2.5h will be soaked during pretreatment cancellous bone adds to the dibastic sodium phosphate aqueous solution that mass concentration is 2.5%, Obtain modified cancellous bone；

During mixture is carried out the step of pH is adjusted in step 4, pH value to 7 is reconciled；In the treatment of first time ice bath, stirring speed It is 500r/min to spend, and process time is 2h；In second ice bath treatment, mixing speed is 500r/min, and process time is 2h；The After the step of secondary ice bath is processed and before drying, 4 hours are stood at a temperature of 25 DEG C.Change collagen acetic acid solution and β turns Change the addition of growth factor.Dosage of crosslinking agent is the 0.01% of collagen.

In the bone renovating material for finally giving, the weight ratio of hydroxyapatite and bata-tricalcium phosphate is 4:6, β conversion growths The content of the factor is relative to the 10ng/g of hydroxyapatite and bata-tricalcium phosphate gross weight；The content of collagen is relative to hydroxyl The 10% of apatite and bata-tricalcium phosphate gross weight.

Embodiment 4

Preparation technology is same as Example 1, and difference is：

3h will be soaked during pretreatment cancellous bone adds to the dibastic sodium phosphate aqueous solution that mass concentration is 3%, obtain in step 2 Modified cancellous bone；

During mixture is carried out the step of pH is adjusted in step 4, pH value to 8.5 is reconciled；In the treatment of first time ice bath, stirring Speed is 500r/min, and process time is 2h；Without second ice bath treatment；Before drying, 4 hours are stood at a temperature of 25 DEG C. Change the addition of collagen acetic acid solution and β TGFs.

In the bone renovating material for finally giving, the weight ratio of hydroxyapatite and bata-tricalcium phosphate is 3:7, β conversion growths The content of the factor is relative to the 0.5ng/g of hydroxyapatite and bata-tricalcium phosphate gross weight；The content of collagen is relative to hydroxyl The 4% of base apatite and bata-tricalcium phosphate gross weight.Dosage of crosslinking agent is the 0.0005% of collagen.

Embodiment 5

Preparation technology is same as Example 1, and difference is：

In step 2 0.5h will be soaked during pretreatment cancellous bone adds to the dibastic sodium phosphate aqueous solution that mass concentration is 0.4%, Obtain modified cancellous bone；

During mixture is carried out the step of pH is adjusted in step 4, pH value to 8 is reconciled；In the treatment of first time ice bath, stirring speed It is 500r/min to spend, and process time is 2h；Without second ice bath treatment；Before drying, 4 hours are stood at a temperature of 25 DEG C.Change The addition of metaeollagen acetic acid solution and β TGFs.

In the bone renovating material for finally giving, the weight ratio of hydroxyapatite and bata-tricalcium phosphate is 9:1, β conversion growth The content of the factor is relative to the 0.5ng/g of hydroxyapatite and bata-tricalcium phosphate gross weight；The content of collagen is relative to hydroxyl The 4% of base apatite and bata-tricalcium phosphate gross weight.It is not added with crosslinking agent.

Performance detection：Obtained bone renovating material in embodiment 1 to 5 is (right with commercially available Bio-Oss Collagen materials Ratio 1, not comprising collagen and growth factor) carry out respectively beasle dog alveolar ridge site retain experiment, it is postoperative can and postoperative 2 Month, to beasle dog row CBCT scan, as a result confirm 2 months after the implantation, using different materials beasle dog height of alveolar ridge and The decreasing value of width is as shown in table 1 respectively：

Table 1

As can be seen from the above description, the above embodiments of the present invention realize following technique effect：Using this hair The bone renovating material prepared in bright embodiment, the bone height of beasle dog and the decreasing value of width are relatively low, and this illustrates that this material exists Promoting bone repair aspect has advantage.

In a word, propagation, differentiation of the bone renovating material that the present invention is provided beneficial to osteocyte.Simultaneously include hydroxyapatite and Bata-tricalcium phosphate, overcomes the shortcoming that hydroxyapatite is excessively stablized, bata-tricalcium phosphate degraded is too fast, balances the degraded of material Speed, makes its matching skeleton preferably repair speed.Collagen can promote cell migration, stick, breaks up and adjust cell life It is long.β TGFs can promote propagation and the differentiation of periosteum mesenchymal cell, promote the propagation of skeletonization (cartilage) cell, thorn Swash the synthesis of collagen, bony union element and osteopontin.Meanwhile, TGF-β can suppress the generation of osteoclast and ripe osteoclastic thin The activity of born of the same parents, so as to suppress bone resorption.As can be seen here, TGF-β plays highly important work during metabolism of bone tissue With.In a word, the bone renovating material that the present invention is provided has had any of the above advantage concurrently, can match the reparation speed of skeleton, Meet the Bone Defect Repari demand at defect of human body bone.

The preferred embodiments of the present invention are the foregoing is only, is not intended to limit the invention, for the skill of this area For art personnel, the present invention can have various modifications and variations.It is all within the spirit and principles in the present invention, made any repair Change, equivalent, improvement etc., should be included within the scope of the present invention.