CN103182099B - Porous active artificial bone and preparation method thereof - Google Patents
Porous active artificial bone and preparation method thereof Download PDFInfo
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Abstract
The invention relates to a porous active artificial bone. In the porous active artificial bone, a calcium phosphate-based biological ceramic material is used as a matrix, and the porous active artificial bone comprises small pores, dense parts and directional pore channels and chelates with diphosphonate. A preparation method of the porous active artificial bone comprises the steps of preparing calcium phosphate precursor powder, compression molding a ceramic blank by using a pore-foaming agent, polyester fiber and the precursor powder, high temperature sintering into a calcium phosphate-based ceramic sintered body and forming the dense parts, the small pores distributed alternately; and immersing calcium phosphate-based ceramic sintered body in a diphosphonate solution to chelate with the diphosphonate so as to obtain the drug-loaded porous active artificial bone. The artificial bone provided by the invention has longitudinal directional pores and a porous structure suitable for osteoblast migration, propagation and growth metabolism, can slowly release small molecular drugs capable of promoting the growth of the osteoblast and inhibiting osteoclast, and is particularly suitable for the fields of treating bone defects of osteoporosis patients, dental restoration, and the like.
Description
Technical field
The invention belongs to biology medical material technical field, relate to a kind of preparation method with the porous active artificial bone in radial duct.
Background technology
In modern medical service field, the bone defect healing problem caused by wound, infection, tumor resection and osteomyelitis etc. is one of difficult problem of plastic surgery and field of orthopaedics always.
Artificial bone or skeletal grain material is generally used to carry out Plugging to small size defect at present, and for large-scale Cranial defect, defect in multiplex autologous bone or allogenic bone transplantation to patient body, why less for large scale Cranial defect current artificial bone is clinically, mainly because it is difficult to reach requirement in mechanical property and aperture structure etc., and artificial bone is next or slightly inferior compared with autologous bone on repairing effect.
Artificial bone mainly uses calcium phosphate ceramics at present clinically.Calcium phosphate ceramics material has good biocompatibility, excellent osteoconductive potential, and can promote that bone medium vessels is formed.Common calcium phosphate ceramic artificial bone mainly divides porous type and compact-type two kinds, compact-type artificial bone common intensity is high, the bone defect healing of weight bearing area can be used for, but due to its structure lacking hole, be unfavorable for osteoblasticly growing into, metabolism exchange and body fluid circulatory, be therefore unfavorable for osteoblastic adhesion, propagation and new bone formation.Porous type artificial bone then generally has higher porosity and larger aperture, can provide good environment, but intensity is general lower, cannot be used for the reparation of weight bearing area Cranial defect for osteoblastic growth, propagation, metabolic activity and nutrient substance exchange.Therefore, preparation has higher force intensity, has the artificial bone of the aperture structure of applicable bone cell growth simultaneously, has very important clinical value.
Use more bone block of material in the market except bone-xenograft, mainly the mixture of β-TCP or β-TCP and HA, they have many advantages, particularly in bone conductibility and cell compatibility, have clear superiority.But not there is the aperture structure of applicable Oesteoblast growth mostly, can not effectively carry products of cellular metabolism and nutrient substance, be unfavorable for migration and the propagation of cell, and be unfavorable for vascularization.
Other coprecipitation method of the prior art, centrifugal, dry or Ginding process are also applicable to this step, according to specific needs, optionally carry out above technique, also can select other technique of prior art, thus obtain the calcium phosphate precursor powder of step 1 of the present invention.
Porogen described in step 2 (being also called pore-creating medium), includes but not limited to one or more in stearic acid, acrylamide polymer, polystyrene, polymethyl methacrylate.Porogen and polyester fiber are with (5 ~ 10): the mass ratio of 1 mixes, then are ceramic body with precursor powder at mould shaped by fluid pressure.Be specially: be that respectively the precursor powder of 20 ~ 50%, the porogen of 40 ~ 80% such as stearic acid and polyester fiber, 0 ~ 10% concentration are that 1 ~ 10% binding agent such as PVA solution mixes by mass percent, shaped by fluid pressure in a mold, makes closely knit ceramic body.Stainless steel mould can be used to be pressed.Preferably, polyester fiber is longitudinally arranged in a mold.Keep certain hour as 10 ~ 60 seconds with certain pressure as 10 ~ 20MPa pressure in mould, thus make closely knit ceramic body.
Advanced row can be selected in step 3 predrying except no-bonder, specifically can comprise following technique:
1) by the ceramic body that step 2 is compressing in a mold, in 70 ~ 120 DEG C of dryings, binding agent is removed in fusing, and places in drying place after being cooled to room temperature state gradually;
2) by dried base substrate, proceed to high temperature furnace, at 800 ~ 1150 DEG C of sintering, heating rate can be 6 ~ 12 DEG C/min, temperature retention time 1 ~ 4h, afterwards furnace cooling, the obtained sintered body with aperture, dense portion and directional hole passage.
In this step 4, described diphosphonate can be the mixture of one or more compositions in Alendronate sodium, neridronic acid sodium, olpadronic acid sodium, risedronate sodium and ibandronic acid sodium, Zoledronic Acid.Step 4 specifically can comprise following technique:
A) the calcium phosphate ceramic sintered body of step 3 gained being immersed concentration is in the bisphosphonate solutions of 0.1 ~ 10 μ g/mL, is placed in constant temperature (temperature is arranged on a certain value within the scope of 25 to 37 ° of C) shaking table 12 ~ 24h; Then take out and clean sintered body gently at least 3 times with deionized water, to utilize calcium ion to the chelation of diphosphonate, diphosphonate in load on sintered body matrix;
B) by step a) gained block (load has the calcium phosphate ceramic sintered body of diphosphonate) with 70 ~ 120 DEG C of dryings;
C) needed according to application by step b) gained sintered body, processing, screening are the artificial bone of different size and shape, for bone defect healing.
Step b) and other Method and process of c) also applicable prior art.
Artificial bone main component of the present invention is calcium orthophosphate base bioceramic, there is good bone conductibility and biocompatibility, by adjusting ratio, reaction system pH scope, the sintering temperature of reaction raw materials, crystalline phase component ratio in end product can be regulated and controled, reached this bone block of adjustment degradation rate in vivo.When this obtained artificial bone is in time block, its mechanical strength controls by moulding process and porogen content, and its aperture structure and porosity also can be controlled by these process conditions as required.Its radial channel diameter and length are by the state modulator of polyester fiber.Radial channel diameter is generally preferably 30 ~ 120 μm, and length is determined according to bone block size, runs through.Its drug loading controls by the concentration of chelating diphosphonate used.
Artificial bone of the present invention has loose structure and the adjustable feature of dense layer ratio, can regulate the mechanical strength of artificial bone easily.This adjustment can be controlled by the content of porogen, hydraulics and binder content.Wherein, reduce porogen content, increase hydraulic pressure or increase in dwell time, certain limit and reduce the mechanical strength that binder content all can improve artificial bone to a certain extent.
Below for concrete example, drug-loaded artificial bone of the present invention and preparation method thereof is described, but not as the restriction of scope.
Example one:
This example artificial bone is a kind of drug-loaded artificial bone with aperture, dense portion and directional hole passage, main component is calcium orthophosphate base bioceramic material, comprise dense portion, aperture be alternately distributed, and in radial design the radial duct of convenience conveying cell nutrient solution, metabolite, body fluid.Wherein, the dense layer wall thickness of artificial bone is about 100 ~ 300 μm, small aperture size 200 ~ 600 μm, and porosity is 30 ~ 70%, and radial channel diameter is 40 ~ 70 μm, comprcssive strength 10 ~ 20MPa, and composition is ultrapure β-TCP, and its phase content is more than 99%.The concentration of load Allan sodium phosphate is 0.1 ~ 10 μ g/ml, and actual drug loading is as the criterion with ultraviolet spectrophotometer test.
The preparation technology of the present embodiment artificial bone comprises the following steps:
Step 1: prepare calcium phosphate precursor powder;
Step 2: be prepared into ceramic body in a mold by pore-creating medium and precursor powder;
Step 3: high temperature sintering;
Step 4: Composite Double phosphonate, prepares drug-loaded artificial bone of the present invention.
Wherein, step 1 concrete technology comprises:
(1) by mol ratio be 1.5 certain density lime nitrate and ammonium dibasic phosphate solution mixing, the pH value to 11 of calcium nitrate solution is adjusted with strong aqua ammonia, adjust the pH value to 10.6 of ammonium dihydrogen phosphate, by ammonium dihydrogen phosphate constant flow pump with in the speed of 1mL/min instillation calcium nitrate solution, vigorous stirring, make it sustained response 12 ~ 24h, obtain calcium phosphate precursor pulp;
(2) by calcium phosphate presoma slurry with 2000 ~ 3000rpm repeatedly centrifugal, washing, obtain presoma block;
(3) be scattered in the inhibitor ammonium sulfate solution of mass percentage concentration wt=1 ~ 5% by presoma block, repeat dispersed with stirring, mix homogeneously forms suspension;
(4) by gained suspension buchner funnel sucking filtration in (3), obtain block of just expecting, be placed in 90 DEG C of air dry ovens oven dry and spend the night;
(5) take out oven dry block, with the fine grinding of agate mortar, be saved to exsiccator for subsequent use.
The concrete technology of step 2 is:
By the precursor powder of the step 1 of mass content 30%, 60% porogen stearic acid and polyester fiber, 10% concentration be 3% binding agent PVA solution mix homogeneously, wherein polyester fiber is longitudinally arranged along mould, and keep one minute with 10MPa pressure in a mold, make closely knit ceramic body.
The concrete technology of step 3 is:
1) by the ceramic body that step 2 is obtained, with 110 DEG C of dryings, binding agent is removed in fusing, and places in drying place after being cooled to room temperature state gradually;
2) proceed to high temperature furnace, with 1050 DEG C of sintering, heating rate 8 DEG C/min, temperature retention time 1h, afterwards furnace cooling, obtain sintered body.
The concrete technology of step 4 is:
A) immersed by step 3 gained sintered body in the alendronic Acid sodium solution of 1 ~ 10 μ g/ml, on 37 DEG C of shaking tables, 30 ~ 70rpm shakes 12h;
B) by a) gained block is clean with deionized water, 70 ~ 110 DEG C of dry 12h;
C) by b) gained sintered body is according to application needs, the artificial bone that processing, screening are different size and shape, for bone defect healing.
Summary of the invention
The technical problem underlying that the present invention solves is to provide a kind of porous active artificial bone and preparation method thereof, thus bone renovating material does not have radial duct and loose structure in solution prior art, mechanical strength is lower, is unfavorable for the problem such as circulation and vascularization of osteoblastic growth, body fluid.
For solving the problems of the technologies described above, providing a kind of porous active artificial bone, with calcium orthophosphate base bioceramic material for matrix, comprising dense portion, alternatively distributed aperture and radial duct, and be chelated with diphosphonate and carry out slow release; This radial duct is the radial duct of carrying cell nutrient solution, metabolite body fluid along the convenience of matrix radial design.
Described small aperture is 100 ~ 1000 μm, and overall porosity is about 30 ~ 70%; Whole matrix is run through in radial duct, and its diameter is 30 ~ 120 μm; The medicine carrying concentration of described load diphosphonate is 0.1 ~ 10 μ g/mL; Comprcssive strength 10 ~ the 30MPa of described artificial bone.
Described calcium orthophosphate base bioceramic material comprises tricalcium phosphate β-TCP, and its mass percent is 20 ~ 100%; Described diphosphonate is the mixture of one or more compositions be selected from Alendronate sodium, neridronic acid sodium, olpadronic acid sodium, risedronate sodium and ibandronic acid sodium, Zoledronic Acid.It is 0 ~ 80% hydroxyapatite HA that described calcium orthophosphate base bioceramic material also can comprise mass percent further.
The present invention also provides the preparation method of described artificial bone, mainly comprises the following steps:
Step 1: prepare calcium phosphate precursor powder;
Step 2: by porogen and polyester fiber and precursor powder compressing ceramic body in a mold;
Step 3: high temperature sintering becomes calcium phosphate ceramic sintered body, and on the matrix of sintered body, form the structure with dense portion, alternatively distributed aperture and radial duct;
Step 4: step 3 gained calcium phosphate ceramic sintered body is immersed certain density bisphosphonate solutions and carries out chelating diphosphonate, thus the porous active artificial bone obtaining medicine carrying.
Described step 1 carries out coprecipitation reaction under certain condition by calcium source solution and phosphorus source solution, pulverizes after clean dry; In described step 2, porogen and polyester fiber are with (5 ~ 10): the mass ratio of 1 mixes; First carry out in described step 3 predryingly sintering again; In step 4, described diphosphonate is the mixture of one or more compositions be selected from Alendronate sodium, neridronic acid sodium, olpadronic acid sodium, risedronate sodium and ibandronic acid sodium, Zoledronic Acid.
Described step 1 comprises following technique further:
A) by mol ratio be 1.2 ~ 1.7 certain density calcium source solution and phosphorus source solution mixing, control ph is reacted under the condition of 10 ~ 12, obtains calcium phosphate presoma slurry;
B) by centrifugal for calcium phosphate presoma slurry, washing, drying, precursor powder is obtained;
C) in precursor powder, be mixed into the inhibitor that mass percent is 0.2 ~ 5%, ground and mixed is even; Inhibitor is be selected from one or more in ammonium sulfate, magnesium sulfate or sodium sulfate, and inhibitor can be aqueous solution or pressed powder.
Described step 2 comprises: mass percent is respectively the precursor powder of 20 ~ 50%, the porogen of 40 ~ 80% and polyester fiber, 0 ~ 10% binding agent mixing, shaped by fluid pressure in a mold, makes closely knit ceramic body; Wherein, described hydraulics is: 10 ~ 20MPa; In a mold, polyester fiber is longitudinally arranged.Described porogen is one or more in stearic acid, acrylamide polymer, polystyrene, polymethyl methacrylate; Described binding agent to be mass percentage concentration be 1 ~ 10% PVA solution.
Step 3 is further comprising the steps:
A) by the ceramic body that step 2 is compressing in a mold, with 70 ~ 120 DEG C of dryings, binding agent is removed in fusing;
B) by dried base substrate, high temperature furnace is proceeded to, with 800 ~ 1100 DEG C of sintering, the obtained sintered body with aperture, dense portion and directional hole passage.
Technique scheme at least has following beneficial effect:
This technology can prepare a kind of medicament slow release type artificial bone with radial duct and loose structure, and it has higher mechanical strength, and can ensure again osteoblastic growth, the circulation of body fluid and vascularization, excellent performance, purposes is more extensive simultaneously.Artificial bone of the present invention has following characteristics:
Artificial bone main component of the present invention is calcium orthophosphate base bioceramic, there is good bone conductibility and biocompatibility, by adjusting ratio, reaction system pH scope, the sintering temperature of reaction raw materials, crystalline phase component ratio in end product can be regulated and controled, reached this bone block of adjustment degradation rate in vivo;
Artificial bone of the present invention has loose structure and the adjustable feature of dense layer ratio, can regulate the mechanical strength of artificial bone easily.This adjustment can be controlled by the content of porogen, hydraulics and binder content;
Artificial bone of the present invention constructs the loose structure that radial duct and intercommunicating pore combine, and is conducive to osteoblasticly growing into, breeding, and the exchange of its metabolite and nutrient substance, can accelerate the reconstruction of Cranial defect.
Further, artificial bone of the present invention utilizes the effect of calcium ion, and chelating has the diphosphonate of osteoporosis therapy effect, can effective slow release this medicine, reaches Oesteoblast growth stimulating, suppresses the effect of osteoclast.
Artificial bone preparation method of the present invention, its technique is simple, and cost is lower, can mass production, has broad application prospects in bone defect healing.By regulating the content of porogen, hydraulics and binder content to control and regulate loose structure and dense layer ratio, and then regulate the mechanical strength of artificial bone.
Detailed description of the invention
A kind of porous active artificial bone of the present invention, be with calcium orthophosphate base bioceramic material for matrix, comprise dense portion, alternatively distributed aperture and run through the radial pore passage structure of whole base bulk, and be chelated with diphosphonate and carry out slow release.This radial duct is the radial duct that the convenience of matrix radial design carries cell nutrient solution, metabolite body fluid.
Small aperture is preferably 100 ~ 1000 μm.The overall porosity of matrix is about 30 ~ 70%.The diameter in radial duct is about 30 ~ 120 μm, and whole block is run through in duct.The medicine carrying concentration of load diphosphonate is 0.1 ~ 10 μ g/mL.Comprcssive strength 10 ~ the 30MPa of this bone of people.
Bone block entirety, in cylindric, block and other controllable shape, is determined according to mould difference.Bone block can do obturator use after fragmentation, and granular size is adjustable.
When this artificial bone is in time block, its mechanical strength controls by moulding process and porogen content, and its aperture structure and porosity also can be controlled by these process conditions as required.Its radial channel diameter and length are by the state modulator of polyester fiber.Radial channel diameter is generally preferably 30 ~ 120 μm, and length is determined according to bone block size, runs through.Its drug loading controls by the concentration of the diphosphonate soaked.
Wherein, the matrix of drug-loaded artificial bone can be block or granular porous ceramics, and it can be made up of pure bata-tricalcium phosphate (β-TCP), can be also that the β-TCP of x% and y% hydroxyapatite HA are formed by mass percent, wherein x=20 ~ 100%, y=0 ~ 80%.
For meeting multiple environment for use requirement, devising a series of component ratio, comprising pure β-TCP, or x% β-TCP and y% HA, wherein x=20 ~ 100%, y=0 ~ 80%.This component ratio can be regulated and controled by the factor such as rate of charge, reaction system pH, sintering temperature of raw material lime nitrate and Ammonium biphosphate.The method that the present invention prepares artificial bone belongs to Wet Method Reaction, higher to the required precision of pH in course of reaction and temperature, Ca/P, and therefore building-up process condition controls comparatively strict.
The method that the present invention prepares above-mentioned artificial bone mainly comprises some steps:
Step 1: prepare calcium phosphate precursor powder;
Step 2: by porogen and polyester fiber and precursor powder compressing ceramic body in a mold;
Step 3: high temperature sintering becomes calcium phosphate ceramic sintered body, and on the matrix of sintered body, form the structure with dense portion, alternatively distributed aperture and radial duct;
Step 4: step 3 gained calcium phosphate ceramic sintered body is immersed certain density bisphosphonate solutions and carries out chelating diphosphonate, thus the porous active artificial bone obtaining medicine carrying.
Wherein, in this step 1, calcium source solution and phosphorus source solution carry out coprecipitation reaction under certain condition, pulverize after clean dry.Described calcium source solution includes but not limited to lime nitrate, calcium chloride.Described phosphorus source solution includes but not limited to sodium hydrogen phosphate, Ammonium biphosphate, diammonium phosphate, phosphoric acid.In the present embodiment, step 1 specifically can comprise following technique:
(1) be in molar ratio 1.2 ~ 1.7 certain density calcium source solution (as calcium nitrate solution) and phosphorus source solution (ammonium dibasic phosphate solution) mixing, under the condition of pH=10 ~ 12 react 12 ~ 24h, obtain calcium phosphate presoma slurry;
(2) by centrifugal with 1000 ~ 4000rpm for calcium phosphate presoma slurry, washing, and in 60 ~ 100 DEG C of dryings, precursor powder is obtained;
(3) in precursor powder, be mixed into the inhibitor that mass percent is 0.2 ~ 5%, ground and mixed is even.Inhibitor includes but not limited to one or more in ammonium sulfate, magnesium sulfate or sodium sulfate, and inhibitor can be aqueous solution or pressed powder.
Embodiment two:
This example artificial bone is a kind of artificial bone with aperture, dense portion and directional hole passage, main component is calcium orthophosphate base bioceramic material, comprise dense portion, aperture alternately occurs, and in radial design the radial duct of convenience conveying cell nutrient solution, metabolite, body fluid, and back loading two kinds of diphosphonates.Wherein, the dense layer wall thickness of artificial bone is about 100 ~ 200 μm, pore size 200 ~ 400 μm, porosity is 50 ~ 70%, and radial channel diameter is 40 ~ 60 μm, comprcssive strength 10 ~ 20MPa, composition is β-TCP and HA, and wherein thing phase β-TCP content is about 80%, HA content is about 20%.Alendronate sodium and risedronate sodium mixed solution concentration are 2 ~ 8 μ g/ml.
The preparation technology of the present embodiment artificial bone comprises the following steps:
Step 1: prepare calcium phosphate precursor powder;
Step 2: be prepared into ceramic body in a mold by pore-creating medium and precursor powder;
Step 3: high temperature sintering;
Step 4: Composite Double phosphonate, prepares drug-loaded artificial bone of the present invention.
Wherein, the concrete technology of step 1 is:
(1) by mol ratio be 1.5 certain density lime nitrate and ammonium dibasic phosphate solution mixing, the pH value to 11.0 of calcium nitrate solution is adjusted with strong aqua ammonia, adjust the pH value to 9.75 of ammonium dihydrogen phosphate, by ammonium dihydrogen phosphate constant flow pump with in the speed of 1mlL/min instillation calcium nitrate solution, vigorous stirring, make it sustained response 12 ~ 24h, obtain calcium orthophosphate base precursor pulp;
(2) by calcium orthophosphate base presoma slurry with 2000 ~ 3000rpm repeatedly centrifugal, washing, obtain presoma block;
(3) presoma block is placed in air dry oven to spend the night with 90 DEG C of oven dry, then uses the fine grinding of agate mortar, be saved to exsiccator for subsequent use;
(4) in (3) gained powder, add the ammonium sulfate solids powder of 1% mass fraction, ground and mixed is even.
The concrete technology of described step 2 is: by the precursor powder of the step 1 of mass content 30%, 65% porogen stearic acid and polyester fiber, 5% binding agent PVA solution (concentration is 3% wt/v) mix homogeneously, wherein polyester fiber is longitudinally arranged, and keep several minutes with 10MPa pressure in a mold, make closely knit ceramic body.
The concrete technology of described step 3 comprises:
1) by the base substrate that step 2 is obtained, predrying with 110 DEG C, binding agent is removed in fusing, and places in drying place after being cooled to room temperature state gradually;
2) by the base substrate of (1) process gained, proceed to high temperature furnace, with 1150 DEG C of sintering, heating rate 8 DEG C/min, temperature retention time 2h, afterwards furnace cooling, obtain sintered body.
The concrete technology of step 4 comprises:
A) by the Alendronate sodium of step 3 gained sintered body immersion 2 ~ 8 μ g/mL and risedronate sodium mixed solution, on 37 DEG C of shaking tables, 12h is shaken with 30 ~ 70rpm;
B) by a) gained block is clean with deionized water, 70 ~ 110 DEG C of dry 12h;
C) by b) gained sintered body is according to application needs, the artificial bone that processing, screening are different size and shape, for bone defect healing.
Load diphosphonate in the artificial bone of the above-mentioned example of the present invention, because of the pyrophosphoric acid analog that diphosphonate is a class synthetic, it is the newtype drug of potent suppression bone resorption, it is combined specifically with hydroxyapatite, but not resemble pyrophosphate in vivo easily degrade by pyrophosphatase, this is the clinical practice basis of diphosphonate.Experiment proves that it can suppress full knee joint and the postoperative bone loss of full marrow Endoprostheses, continue to improve the bone density around articular prosthesis, suppress the release such as macrophage and the osteoblast osteolytic factor, the bone of wear particle induction is suppressed to dissolve, promote osteoblastic propagation, improve osteoblast activity, be suppressed to apoptosis of bone cells and osteoclastic bone resorption, the apoptosis of acceleration osteoclast.Further, above-mentioned artificial bone has the drug slow release function of radial duct and loose structure, and it has higher mechanical strength, and can ensure again osteoblastic growth, the circulation of body fluid and vascularization, excellent performance, purposes is more extensive simultaneously.
Experiment proves, artificial bone of the present invention constructs the loose structure that radial duct and intercommunicating pore combine, and is conducive to osteoblasticly growing into, breeding, and the exchange of its metabolite and nutrient substance, can accelerate the reconstruction of Cranial defect.And the calcium ion that artificial bone of the present invention utilizes its matrix to exist, chelating has the diphosphonate of osteoporosis therapy effect, can effective slow release this medicine, reaches Oesteoblast growth stimulating, suppresses the effect of osteoclast.
Artificial bone preparation method of the present invention, its technique is simple, and cost is lower, can mass production, has broad application prospects in bone defect healing.By regulating the content of porogen, hydraulics and binder content to control and regulate loose structure and dense layer ratio, and then regulate the mechanical strength of artificial bone.
Claims (8)
1. a preparation method for porous active artificial bone, its preparation method comprises the following steps:
Step 1: prepare calcium phosphate precursor powder;
Step 2: by porogen and polyester fiber and precursor powder compressing ceramic body in a mold: specifically described porogen and polyester fiber are with (5 ~ 10): the mass ratio of 1 mixes; Mass percent is respectively the precursor powder of 20 ~ 50%, the porogen of 40 ~ 80% and polyester fiber, 0 ~ 10% binding agent mixing, shaped by fluid pressure in a mold, makes closely knit ceramic body; Wherein, described hydraulics is: 10 ~ 20MPa; Polyester fiber is arranged along the longitudinal direction of mould;
Step 3: high temperature sintering becomes calcium phosphate ceramic sintered body, and on the matrix of sintered body, form the structure with dense portion, alternatively distributed aperture and radial duct;
Step 4: step 3 gained calcium phosphate ceramic sintered body is immersed certain density bisphosphonate solutions and carries out chelating diphosphonate, thus the porous active artificial bone obtaining medicine carrying;
Obtained artificial bone be with calcium orthophosphate base bioceramic material for matrix, comprise dense portion, alternatively distributed aperture and radial duct, and be chelated with diphosphonate and carry out slow release; This radial duct is the radial duct of carrying cell nutrient solution, metabolite body fluid along the convenience of matrix radial design; The diameter in described radial duct is 30 ~ 120 μm.
2. the preparation method of artificial bone as claimed in claim 1, it is characterized in that: described small aperture is 100 ~ 1000 μm, overall porosity is 30 ~ 70%; Described radial hole length is determined according to bone block size, and whole matrix is run through in radial duct; The medicine carrying concentration of described load diphosphonate is 0.1 ~ 10 μ g/mL; Comprcssive strength 10 ~ the 30MPa of described artificial bone.
3. the preparation method of artificial bone as claimed in claim 1, it is characterized in that: described calcium orthophosphate base bioceramic material comprises tricalcium phosphate β-TCP, its mass percent is 20 ~ 100%; Described diphosphonate is the mixture of one or more compositions be selected from Alendronate sodium, neridronic acid sodium, olpadronic acid sodium, risedronate sodium and ibandronic acid sodium, Zoledronic Acid.
4. the preparation method of artificial bone as claimed in claim 3, is characterized in that: it is 0 ~ 80% hydroxyapatite HA that described calcium orthophosphate base bioceramic material comprises mass percent further.
5. the preparation method of artificial bone as claimed in claim 1, is characterized in that: described step 1 carries out coprecipitation reaction under certain condition by calcium source solution and phosphorus source solution, pulverizes after clean dry; First carry out in described step 3 predryingly sintering again; In step 4, described diphosphonate is the mixture of one or more compositions be selected from Alendronate sodium, neridronic acid sodium, olpadronic acid sodium, risedronate sodium and ibandronic acid sodium, Zoledronic Acid.
6. the preparation method of artificial bone as claimed in claim 1, is characterized in that: described step 1 comprises following technique further:
A) by mol ratio be 1.2 ~ 1.7 certain density calcium source solution and phosphorus source solution mixing, react under the condition of pH=10 ~ 12, obtain calcium phosphate presoma slurry;
B) by centrifugal for calcium phosphate presoma slurry, washing, drying, precursor powder is obtained;
C) in precursor powder, be mixed into the inhibitor that mass percent is 0.2 ~ 5%, ground and mixed is even; Inhibitor is be selected from one or more in ammonium sulfate, magnesium sulfate or sodium sulfate, and inhibitor can be aqueous solution or pressed powder.
7. the preparation method of artificial bone as claimed in claim 1, is characterized in that: the porogen of described step 2 is one or more in stearic acid, acrylamide polymer, polystyrene, polymethyl methacrylate; Described binding agent to be mass percentage concentration be 1 ~ 10% PVA solution.
8. the preparation method of artificial bone as claimed in claim 1, is characterized in that: step 3 is further comprising the steps:
A) by the ceramic body that step 2 is compressing in a mold, with 70 ~ 120 DEG C of dryings, binding agent is removed in fusing;
B) by dried base substrate, high temperature furnace is proceeded to, with 800 ~ 1150 DEG C of sintering, the obtained sintered body with aperture, dense portion and directional hole passage.
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| CN110451979A (en) * | 2019-08-19 | 2019-11-15 | 上海应用技术大学 | A kind of preparation method of the screen like and porous ceramic with double through type hole hole |
| CN110568114B (en) * | 2019-08-29 | 2021-12-28 | 福州佳宸生物科技有限公司 | Solid phase microextraction-high performance liquid chromatography on-line combined detection method for zoledronic acid and risedronic acid |
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| CN101927989A (en) * | 2010-06-04 | 2010-12-29 | 山东轻工业学院 | Method for preparing ordered nest-shaped porous hydroxylapatite material |
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| CN1850293A (en) * | 2006-04-26 | 2006-10-25 | 卢建熙 | Medical reinforced porous biological ceramic, its preparing method and use |
| CN101766843A (en) * | 2010-02-05 | 2010-07-07 | 清华大学 | Artificial bone with porous laminated structure and passages and preparation method thereof |
| CN101927989A (en) * | 2010-06-04 | 2010-12-29 | 山东轻工业学院 | Method for preparing ordered nest-shaped porous hydroxylapatite material |
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| 赵祥波,等.双膦酸盐类药物研究及应用进展.《中国骨质疏松杂志》.2011,第17卷(第10期), * |
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