CN102008752B - Porous biphasic calcium phosphate biological scaffold with nano hydroxyapatite coating and preparation method thereof - Google Patents
Porous biphasic calcium phosphate biological scaffold with nano hydroxyapatite coating and preparation method thereof Download PDFInfo
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- CN102008752B CN102008752B CN 201010580428 CN201010580428A CN102008752B CN 102008752 B CN102008752 B CN 102008752B CN 201010580428 CN201010580428 CN 201010580428 CN 201010580428 A CN201010580428 A CN 201010580428A CN 102008752 B CN102008752 B CN 102008752B
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Abstract
The invention discloses a porous biphasic calcium phosphate biological scaffold with a nano hydroxyapatite coating and a preparation method thereof. The method comprises the following steps of: respectively preparing monoammonium phosphate solution and calcium nitrate tetrahydrate solution; mixing the monoammonium phosphate solution and an adhesive, namely polyvinyl alcohol, heating the mixture to neutralize the mixture, and placing the mixture into the porous biphasic calcium phosphate biological scaffold; adding the calcium nitrate tetrahydrate solution into the reaction system and shaking to uniformly mix; adding the obtained reaction system into a reaction kettle, and heating to react at 120 DEG C for 12 hours; and performing suction filtration, and after repeatedly washing the scaffold with absolute ethanol and double distilled water, drying the scaffold at room temperature. The method improves biocompatibility of a biological scaffold material, contributes to the quick growth of cells and also improves the clinic using value of the biological scaffold material.
Description
Technical field
The present invention relates to the biomedical engineering technology field, specifically based on chemical precipitation method, porous biphasic calcium phosphate biological scaffold is carried out the preparation method of nano hydroxyapatite coating and the biological support that obtains.
Background technology
The treatment that bone is damaged is one of difficult problem of facing of Orthopedic Clinical doctor, autologous bone transplanting is the goldstandard of generally acknowledging, but the size and shape of bone graft is restricted, and often bring for distinguishing complication, limit its application, homogeneous allogenic bone transplantation is also comparatively ideal graft, but may spread disease and cause immunoreation.Although and the bone cement injection is convenient, also can not spread disease, due to the ability that does not have osteanagenesis, usually cause the local bone strength decreased, there are fatal anaphylaxis and heat production.All there is deficiency separately in these methods, are difficult to satisfy the damaged needs of clinical repair bone.The appearing as of tissue engineered bone overcomes above-mentioned deficiency provides new approaches.Its basic ideas are with after living cells In vitro culture propagation, with the substitute of the mutually compound formation bone of timbering material.Desirable bone tissue engineering stent material should possess following characteristics: 1, good bone conductibility has three-dimensional porous stereochemical structure; 2, good biocompatibility; 3, good biological degradability, material itself and catabolite thereof are harmless; 4, has certain mechanical strength; 5, be easy to plasticity.The timbering material that uses at present mainly contains: natural macromolecular material mainly comprises collagen (Col), acellular matrix (ACTM), chitin (CS) and derivant chitosan (having another name called chitosan), fibrin etc., have good biocompatibility, be beneficial to cell adhesion, propagation and differentiation.Synthesized polymer material mainly comprises polyglycolic acid (PGA), polylactic acid (PLA), polycaprolactone (PCL), polylactic-co-glycolic acid (PLGA), polymethyl methacrylate (PMMA) etc.Hydroxyapatite (HA) is the main inorganic composition that consists of biological hard tissue, have lamellar structure and nanocrystalline characteristics, it not only has good biocompatibility, avirulence, can also conduct osteogenesis, cell attachment, stretching, extension can form chemical bonds on the interface with being organized in after implanting, in case can produce bone matrix collagen, then further mineralising, form osseous tissue; But merely HA is come with some shortcomings as the load-carrying member of human body, low such as intensity, elastic modelling quantity is high, fragility is large, poor toughness and molding undesirable etc.β-TCP has good biological degradability, the compatibility and avirulence, the growth of bootable new bone after its implant into body, the calcium of degrading, phosphorus can enter the live body blood circulation and form area of new bone, better bone inductive effect, be its shortcoming but degradation speed is too fast, be unfavorable for adhering to of knitting and cell.Two-phase biological ceramic is mixed by different proportion HA and β-TCP, and (HA or β-TCP), have biological degradability preferably are conducive to induced osteogenesis with respect to single-phase bioceramic.Ramay etc. develop nanometer two-phase porous calcium phosphate support, are comprised of TCP substrate and nanometer hydroxyapatite, and its comprcssive strength and spongy bone are similar after testing, and voidage is 73%.In recent years, along with the development of nanometer knowledge and technology, it is found that the hydroxyapatite in skeleton is mainly nanoscale whiskers body structure.Nano level hydroxyapatite is more similar to human body internal skeleton component of organization, has better biocompatibility.According to " nano effect " theory, the nanoparticle surface of unit mass is long-pending obviously greater than micro-size particles, make the atom number that is in particle surface obviously increase, improved the activity of particle, thereby be beneficial to tissue bond, also help the improvement of mechanical property (intensity, toughness and superplasticity).Compare with common HA, nanometer HA shows higher cell proliferation rate, and along with the reduction of lixiviating solution concentration and the growth of incubation time, cytotoxicity is tending towards 0 grade; The microparticle of nanometer HA and cell direct contacts and has no cytotoxic effect, easily with cell adhesion, growth, and better bio-compatible.And the induced osteogenesis effect of artificial bone is subject to the impact of material void structure, research finds that the larger 400-800 micron in aperture is conducive to the formation of new bone with respect to the small-bore, and the aperture is less than 150 microns, and voidage is grown into less than 30% the new bone of calcium phosphate ceramic significant limitation.
Nanometer hydroxyapatite has better biocompatibility and is conducive to cell adhesion, utilizes nano hydroxyapatite coating to carry out surface modification to biomaterial, and making it to have biological activity is one of direction of research.The preparation method of present nano hydroxyapatite coating has plasma spraying method, laser cladding, electrophoretic deposition, electrochemical deposition method, biomimetic method etc.And focus mostly on and carry out the research of nano hydroxyapatite coating layer preparation in the metal surface.The inorganic matter modifying surface make it to have better biocompatibility and bioactive research at present at home and abroad also between report.The present invention adopts chemical method to produce nanometer hydroxyapatite, directly at porous biphasic calcium phosphate biological scaffold (HA/ β-TCP=6-7/3-4, voidage 40-60%, aperture 100-500 micron) in the hole and surface preparation nano hydroxyapatite coating, to improve the biocompatibility of biologic bracket material, the Fast Growth of favourable cell improves its clinical use value.
Summary of the invention
The purpose of this invention is to provide a kind of in the porous biphasic calcium phosphate biological scaffold hole and the method for surface " coating " nanometer hydroxyapatite, and a kind of like this biological support that obtains, to improve the biocompatibility of biologic bracket material, the Fast Growth of favourable cell improves its clinical use value.
A kind of porous biphasic calcium phosphate biological scaffold with nano hydroxyapatite coating, the outer surface of described biological support and space surface uniform are distributed with 100% (100% refers to purity) hydroxyapatite corynebacterium crystal.
Described hydroxyapatite corynebacterium crystal diameter 20-30 nanometer, length is the 100-200 nanometer.
Described porous biphasic calcium phosphate biological scaffold (hydroxyapatite and bata-tricalcium phosphate mixture, the HA/ β-TCP mass ratio=6-7/3-4 of HA/ β-TCP), voidage 40-60%, aperture 100-500 micron.
A kind of preparation method with porous biphasic calcium phosphate biological scaffold of nano hydroxyapatite coating comprises the following steps:
1) prepare respectively Ammonium biphosphate and four water-calcium nitrate solution;
2) ammonium dihydrogen phosphate and adhesive polyethylene alcohol are mixed, add thermo-neutrality, put into porous biphasic calcium phosphate biological scaffold;
3) four water-calcium nitrate solution is added step 2) in the reaction system that obtains, the concussion mixing;
4) step 3) reaction system that obtains changes in reactor, 120 ℃, continues 12 hours reacting by heating;
5) sucking filtration, after dehydrated alcohol, distilled water cyclic washing, room temperature is dried.
Step 1) concentration of described Ammonium biphosphate and four water-calcium nitrate solution is respectively 0.3mol/L and 0.5mol/L.
Described four water-calcium nitrate: Ammonium biphosphate: the PVA mol ratio is 15: 25: 1.
Step 2) the described thermo-neutrality that adds is after being heated to 80-100 ℃ of stirring and evenly mixing, with strong aqua ammonia, pH value being transferred to 10.5-11.5, then put into porous biphasic calcium phosphate biological scaffold
Step 3) described when adding four water-calcium nitrate solution, under ultrasonic concussion, four water-calcium nitrate solution is splashed into step 2 with 2ml/min) in the reaction system that obtains.
Step 4) described reacting by heating is to insert vacuum drier after reaction system is changed over to reactor.
Described porous biphasic calcium phosphate biological scaffold HA/ β-TCP mass ratio=6-7/3-4, voidage 40-60%, aperture 100-500 micron.
The preparation method of present nano hydroxyapatite coating has plasma spraying method, laser cladding, electrophoretic deposition, electrochemical deposition method, biomimetic method etc.And focus mostly on and carry out the research of nano hydroxyapatite coating layer preparation in the metal surface.The present invention successfully adopts chemical precipitation method that nanometer hydroxyapatite is attached to two-phase tricalcium phosphate multiporous biological support inside and outside surface in the mode of " coating ", makes the biologic bracket material of nanoHA/BCP composite.Prepared nano hydroxyapatite coating first on inorganic material (biphasic calcium phosphate), be conducive to the seed cell marrow stromal cell directly in nano-grade hydroxy apatite surface attachment and growth, take full advantage of nano-grade hydroxy apatite good biocompatibility and biphasic calcium phosphate degradation rate adjustability, so both bring into play cell and be easy to advantage in the growth of nanometer hydroxyapatite surface adhesion, solve simultaneously the difficult problem that nanometer hydroxyapatite is difficult to be shaped, taken into account again single-phase calcium phosphate biodegradation time and the new inconsistent problem of bone formation speed of having solved.This new bio support carries out the model experiment of animal spinal fusion, and result shows that the new bio support more is conducive to the formation with area of new bone of entering of osteocyte.
Description of drawings
Fig. 1 is the BCP support schematic diagram that the present invention prepares;
Fig. 2 is electron-microscope scanning BCP brace aperture of the present invention inner surface figure;
Fig. 3 is BCP support component X ray diffraction diagram of the present invention;
Fig. 4 is electron-microscope scanning BCP bracket coating of the present invention internal pore surface figure;
Fig. 5 is BCP bracket coating component X ray diffraction diagram of the present invention.
Fig. 6 skeletonization figure that is timbering material of the present invention in rabbit spinal fusion sclerous tissues's section space.
The specific embodiment
Only further illustrating the present invention below in conjunction with embodiment, and unrestricted the present invention.
1. the preparation of porous biphasic calcium phosphate biological scaffold:
Prepare by a certain percentage hydroxyapatite (HA), bata-tricalcium phosphate (β-TCP) cross 200 mesh sieves after composite powder, add certain proportion plasticizer (polyvinyl alcohol, PVA), add water furnishing pasty state, fully flood with suitable aperture diameter polyurethane foam, dry at a certain temperature, then at high temperature sintering 2-3 hour, can arrive identical shaped with foam, the space is evenly distributed, aperture diameter is at the compound porous biphasic calcium phosphate support (BCP) of 200-500 μ m.
2. with deionized water preparation 0.3mol/L Ammonium biphosphate and 0.5mol/L four water-calcium nitrate;
3. get the ammonium dihydrogen phosphate that 25ml prepares, heat 80-100 ℃ of magnetic agitation and 0.0005mol PVP fully dissolve mixing, and NH3H2O transfers PH to 10.5-11.5, and the BCP support is put into upper liquid.
4.25ml four water-calcium nitrate solution changes medicine bottle over to, controls by transfusion device and drips speed, under 37 ℃ of water temperatures, under ultrasonic concussion, four water-calcium nitrate liquid at the uniform velocity splashes into the Ammonium biphosphate mixed liquor that contains the BCP support with 2ml/min.Ultrasonic concussion is kept 30 minutes with abundant hybrid reaction.
5. reaction system is inserted vacuum drier after changing reactor over to, 120 ℃, continues 12 hours.
6. after negative pressure leaching, dehydrated alcohol, distilled water cyclic washing 2 times, room temperature is dried and is both obtained being diameter 20-30 nanometer in biological support outer surface and hole, and length is 100-200 nanometer corynebacterium nano hydroxyl phosphorite crystal uniform coating.
Table 1 is that (in employing peak height measurement method BCP support, the content of tricalcium phosphate and hydroxyapatite is respectively 33.9% and 66.1% to BCP support component X ray diffraction diagram analysis indexes of the present invention; The peak area rule is 36.8% and 63.2%)
Table 1
Table 2 is BCP bracket coating component X ray diffraction diagram analysis indexes of the present invention (adopt peak height measurement method and peak area rule BCP bracket coating composition to be hydroxyapatite, purity is 100%)
Table 2
Claims (8)
1. the porous biphasic calcium phosphate biological scaffold with nano hydroxyapatite coating, is characterized in that, the outer surface of described biological support and space surface uniform are distributed with nano-grade hydroxy apatite corynebacterium crystal;
Described hydroxyapatite corynebacterium crystal diameter is the 20-30 nanometer, and length is the 100-200 nanometer.
2. biological support according to claim 1, is characterized in that, described porous biphasic calcium phosphate biological scaffold HA/ β-TCP mass ratio=6-7/3-4, and voidage is 40-60%, the aperture is the 100-500 micron.
3. the described a kind of preparation method with porous biphasic calcium phosphate biological scaffold of nano hydroxyapatite coating of claim 1 or 2, is characterized in that, comprises the following steps:
1) prepare respectively Ammonium biphosphate and four water-calcium nitrate solution;
2) ammonium dihydrogen phosphate and adhesive polyethylene alcohol are mixed, add thermo-neutrality, put into porous biphasic calcium phosphate biological scaffold;
3) four water-calcium nitrate solution is added step 2) in the reaction system that obtains, the concussion mixing;
4) reaction system that step 3) is obtained changes in reactor, 120 ℃, continues 12 hours reacting by heating;
5) sucking filtration, after dehydrated alcohol, distilled water cyclic washing, room temperature is dried.
4. preparation method according to claim 3, is characterized in that, the concentration of the described Ammonium biphosphate of step 1) and four water-calcium nitrate solution is respectively 0.3mol/L and 0.5mol/L.
5. preparation method according to claim 3, is characterized in that, described four water-calcium nitrate: Ammonium biphosphate: the PVA mol ratio is 15:25:1.
6. preparation method according to claim 3, is characterized in that step 2) the described thermo-neutrality that adds is after being heated to 80-100 ℃ of stirring and evenly mixing, with strong aqua ammonia, pH value being transferred to 10.5-11.5, then put into porous biphasic calcium phosphate biological scaffold.
7. preparation method according to claim 3, is characterized in that, step 3) is described when adding four water-calcium nitrate solution, under ultrasonic concussion, four water-calcium nitrate solution is splashed into step 2 with 2mL/min) in the reaction system that obtains.
8. preparation method according to claim 3, is characterized in that, the described reacting by heating of step 4) is to insert vacuum drier after reaction system is changed over to reactor.
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| CN102515849B (en) * | 2011-12-16 | 2014-06-25 | 四川大学 | Porous bioceramic with calcium phosphate nanorods on surface layer and formation method for same |
| CN102727937B (en) * | 2012-06-28 | 2014-03-26 | 哈尔滨工程大学 | Biodegradable zinc (or zinc alloy) and porous biphase calcium phosphate composite material and preparation method thereof |
| CN103341213B (en) * | 2013-06-25 | 2015-06-24 | 上海交通大学 | Preparation method for FHA/beta-TCP (fluorhydroxyapatite/beta-tertiary calcium phosphate) diphasic fluoridated hydroxyapatite 3D (three-dimensional) porous scaffold |
| CN103693995B (en) * | 2013-12-20 | 2016-04-13 | 华南理工大学 | A kind of Ca-P ceramic activating surface and preparation method |
| CN106178127A (en) * | 2016-07-26 | 2016-12-07 | 东华大学 | A kind of original position prepares the method for modified hydroxylapatite/polyvinyl alcohol nano composite membrane |
| CN109020701A (en) * | 2018-09-11 | 2018-12-18 | 浙江世佳科技有限公司 | A kind of high-performance bio bacterial manure |
| CN112642452A (en) * | 2020-11-24 | 2021-04-13 | 清华大学 | Functional heating slurry capable of degrading organic pollutants and preparation method and application thereof |
| GB202111039D0 (en) | 2021-07-30 | 2021-09-15 | Promimic Ab | Materials and methods |
| CN114886782B (en) * | 2022-05-07 | 2023-06-16 | 深圳市博威凯特科技有限公司 | Active calcium compound based on nano hydroxyapatite and preparation method and application thereof |
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| CN101545109A (en) * | 2009-05-08 | 2009-09-30 | 上海理工大学 | Titanium or titanium alloy with surface bioactive layer and preparation method thereof |
| CN101741740A (en) * | 2009-12-15 | 2010-06-16 | 杭州华三通信技术有限公司 | Method, system and equipment for balancing loads |
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| CN101741740A (en) * | 2009-12-15 | 2010-06-16 | 杭州华三通信技术有限公司 | Method, system and equipment for balancing loads |
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