CN103462729B - The preparation method of the biomimetic artificial bone of a kind of multistage [micrometer/nanometer] pore structure - Google Patents

Abstract

The controllable method for preparing of a kind of biomimetic artificial bone three-dimensional multistage pore structure, it is characterized in that: utilize selective laser (spot diameter is micro-meter scale) sintering to realize 150-800 ��m of gradient and run through hole, utilize a small amount of high polymer micro balloons of mixing oxygenolysis in sintering process to form 10-100 ��m of random spherical hole, utilize etching process to obtain the method in irregular hole, tens nanometer surface, finally obtain having the biomimetic artificial bone of the similar three-dimensional multistage pore structure with nature bone. According to implant site requirement, by adjustment sintering process parameter, it is possible to accurately control gradient runs through the distribution in hole and connection property etc.; The shape and size etc. in spherical hole can be controlled by precise hard_drawn tuhes furnace temperature curve and superpolymer particle properties; The size and number etc. of nanoporous can be controlled by control corrosion rate liquid concentration and etching time. This, for creating a kind of microenvironment being beneficial to cell adhesion, proliferation and function performance, promotes new bone formation, accelerates knitting and be extremely important.

Description

The preparation method of the biomimetic artificial bone of a kind of multistage [micrometer/nanometer] pore structure

Technical field

The invention belongs to the bionical manufacture field of bone tissue engineer, particularly when preparing the biomimetic artificial bone of hierarchical porous structure, provide and a kind of utilize selective laser sintering to realize 150-800 ��m of gradient to run through hole, utilize a small amount of high polymer micro balloons of mixing oxygenolysis in sintering process to form 10-100 ��m of random spherical hole, utilize etching process to obtain the method in irregular hole, tens nanometer surface, finally obtain having the biomimetic artificial bone of the similar three-dimensional multistage pore structure with autologous bone.

Technical background

The disappearance of tissue or dysfunction are the great problems threatening human health, are also the ill and dead main reasons of the mankind. Particularly in recent years along with aging population, and the development of the cause such as industry, traffic, physical culture, the reparation of osseous tissue defect and replacing is required day by day urgent by people. For a long time, the bone graft of clinical middle use mainly contains autologous bone and allograph bone, but autologous bone transplanting due to draw materials limited cannot meet big section bone collection requirement and the case of Cranial defect on a large scale, and allogenic bone transplantation slowly affects the functional rehabilitation of patient owing to being replaced process, therefore people thirst for obtaining a kind of to assist new osteanagenesis and source is sufficient, healing time is short biomimetic artificial bone.

Desirable biomimetic artificial bone not only to be provided support structure for defect, the more important thing is and to be created a kind of microenvironment being conducive to cell adhesion, proliferation and function to play, and induction osteocyte generates, and degraded and absorbed gradually, final forms new bone. This requires that biomimetic artificial bone support possesses good biocompatibility and biological activity, and has the microcosmic vesicular structure of applicable growth and proliferation of cell, and with defect coincide profile and enough mechanical strengths etc. Bioactive ceramics mainly comprises hydroxyapatite (HAP), calcium phosphate (TCP) and bio-vitric (BG) etc., owing to having good biocompatibility, degradation property and osteoconductive, go out good affinity with cells show, it is considered as current most potential bone alternate material.

How to realize the three-dimensional porous structure consistent with nature bone to create the microenvironment being suitable for cellular activity, procreation, it is the key that can artificial bone scaffold play optimum skeletonization usefulness. nature bone is a kind of material with three-dimensional multistage pore structure, aperture is from tens nanometer to hundreds of micron, the growth requirement of different tissues can be met, wherein the aperture of 150-800 ��m is conducive to osseous tissue, growing into of blood vessel, the aperture of 10-100 ��m allows growing into of capillary vessel, promote the exchange of nutritive substance and the discharge of meta-bolites, the aperture of nanoscale can provide bigger specific surface area and more active target spot, be conducive to shape core and the protein of phosphatic rock, the absorption of scleroblast, the adhesion of cell and migration propagation had important regulating effect simultaneously. the bionical manufacture of artificial bone scaffold is proposed great challenge by the structure in this kind of three-dimensional multistage hole.

The traditional method preparing vesicular structure at present mainly contains chemical blowing process, adds pore-forming material method, partly sinters reaming method, organic backbone transfer printing, sinters microballoon method etc. Chemical blowing process is material and the ceramic powder mixing moulding that can at high temperature occur chemical reaction to produce gas, and process foaming at a certain temperature produces porous ceramics; Pore-forming material method is by adding pore-forming material in pottery so that it is at high temperature after-flame or volatilization and in pottery, leave hole; Half sintering reaming method is that half sintered body soaks after reaming double sintering again; Organic backbone transfer printing adopts the hole coral with similar spongy bone structure as artificial bone; Sintering microballoon method adds in mould by degradable polymer microspheres, is heated to more than second-order transition temperature, through insulation, cooling, the obtained porous support of the demoulding; Be separated/Emulsion freeze-drying polymers soln, emulsion etc. is separated through cryogenic freezing, then utilizes freeze drying process to remove solvent thus obtain porous support. These methods above-mentioned lack the control to pore structure (such as pore size, space trend and connection property etc.), the more important thing is that pore texture is single, cannot meet the growth requirement of different tissues, and pore texture still has larger difference compared with nature bone.

In sum, seek the bionic preparation that an effective technological approaches realizes artificial bone scaffold three-dimensional multistage hole, to meet in Bone Defect Repari process the growth requirement of different cell, for new osteanagenesis and the healing acceleration time there is important meaning.

Summary of the invention

For the problem that existing method is single to the deficiency of Porosity control and structure, the present invention proposes and a kind of utilize selective laser sintering to realize 150-800 ��m of gradient to run through hole, utilize a small amount of high polymer micro balloons of mixing and oxygenolysis forms 10-100 ��m of random spherical hole, utilizes etching process to obtain the method in irregular hole, tens nanometer surface in sintering process, finally obtaining having the biomimetic artificial bone of the three-dimensional multistage pore structure similar with nature bone, laser spot diameter is micro-meter scale.

The preparation method of the biomimetic artificial bone in the present invention with hierarchical porous structure mainly comprises the following steps:

(1) raw material preparation: add a certain amount of high polymer micro balloons in nano-bioactive ceramic powder, mixed uniformly powder is obtained by mechanical mixing, wherein superpolymer comprises poly(lactic acid) (PLA), polyglycolic acid (PGA), Poly(D,L-lactide-co-glycolide (PLGA) 3 kinds, and the massfraction of superpolymer is 10-40%.

(2) green compact are shaping: uniform laying one layer of mixed powder on sintering platform, powder layer thickness is 0.15-0.2mm, selectively scanning sintered powder according to support two-dimensional section information Control laser beam, by being layering, technology obtains three-dimensional bionic artificial bone scaffold green compact.

(3) clear powder process: sintering platform declines certain height, and after utilizing hairbrush, compressor, air gun or suction cleaner to remove unsintered powder, the gradient obtaining 150-800 ��m runs through hole.

(4) high temperature sintering: the green compact after clear powder are seated in temperature controlling stove and sinter again, and the removal carrying out superpolymer by precise hard_drawn tuhes furnace temperature curve forms the random spherical hole of 10-100 ��m simultaneously.

(5) acid and alkali corrosion: be immersed in by biomimetic artificial bone support in certain density acidity or basic solution and carry out chemical corrosion, takes out support after certain time, utilizes deionized water rinsing and dry, and obtains the surperficial irregular hole of tens nanometer.

Compared with prior art, the advantage of the present invention is:

(1) utilize micron-sized laser hot spot (50 ��m) selectively sintered powder can obtain 150-800 ��m and run through completely gradient pore structured. According to implant site requirement, by processing parameters such as adjustment laser power, sweep span, spot size, sintering paths, it is possible to accurately control gradient runs through the distribution in hole, connection property, porosity etc.

(2) again in sintering process high polymer micro balloons gradually oxygenolysis, discharge until completely dissolve, in nano ceramics, finally form the random spherical hole of 10-100 ��m. According to implant site requirement, the size in formed spherical hole and quantity etc. can be controlled by controlling the shape of superpolymer particle, size and content.

(3) utilize etching process that nano-bioactive ceramics bracket is carried out acid-alkali treatment, obtain the netted hole of nanoscale by changing rack surface shape looks. According to implant site requirement, the size and quantity etc. of nanoporous can be controlled by control corrosion rate liquid concentration and etching time.

(4) controllable method for preparing of a kind of biomimetic artificial bone three-dimensional multistage pore structure is proposed, comprise hundreds of microns of gradients and run through hole, the irregular hole in the random spherical hole of some tens of pm and tens nanometer surface, and by the adjusting process gain of parameter three-dimensional porous structure consistent with nature bone.

Accompanying drawing explanation

Fig. 1 is the selective laser sintering system of self-developing.

Fig. 2 is that the hundreds of microns of gradients utilizing micron-sized laser hot spot to prepare run through hole.

Fig. 3 is the random spherical hole of the some tens of pm utilizing high polymer micro balloons oxygenolysis in sintering process to obtain.

Fig. 4 is the irregular hole, tens nanometer surface utilizing etching process to obtain.

Embodiment

Below by an example, the specific embodiment of the present invention is set forth:

Adopting nanometer hydroxyapatite powder and Poly-L-lactic acid PLLA to be raw material, wherein HAP is minute hand shape, long about 150nm, wide about 20nm, median size 40nm; PLLA median size is 10-100 ��m, and relative viscosity is 0.51-1.0dl/g. Obtaining mixed uniformly PLLA/HAP powder stock by the method for mechanically mixing, wherein PLLA massfraction is 10%. Based on the selective laser sintering system of self-developing, the sinter molding carrying out PLLA/HAP powder under the processing condition of laser spot diameter 50 ��m, paving powder thickness 0.2 ��m obtains support green compact, again green compact are seated in temperature controlling stove and sinter again, and remove the PLLA in green compact by precise hard_drawn tuhes furnace temperature curve. Again support is put into concentration be 10% the corrosion of hydrofluoric acid (HF) solution take out after 10 minutes, with deionized water rinsing 5 minutes and put into 40 DEG C of baking ovens and dry.

Utilize scanning electronic microscope (SEM) that the pore texture of support has been carried out testing and analyzing. In Fig. 2, the hole of hundreds of microns run through completely and porosity higher; Fig. 3 shows to exist in support the spherical hole of some tens of pm, and distribution uniform; Fig. 4 can finding out, rack surface exists hole irregular in a large number after corrosion, size be tens nanometers to tens nanometer not etc. Result of study confirms that the present invention can utilize selective laser (spot diameter is micro-meter scale) sintering to realize 150-800 ��m of gradient and run through hole preparation, utilizes a small amount of high polymer micro balloons of mixing oxygenolysis in sintering process to form 10-100 ��m of random spherical hole, utilizes etching process to form the irregular pore structure in tens nanometer surface, the biomimetic artificial bone of final acquisition and the similar vesicular structure of nature bone, this has important meaning for promotion new bone formation, quickening knitting.

Claims (1)

1. one kind utilizes selective laser sintering to realize 150-800 ��m of gradient to run through hole, utilize a small amount of high polymer micro balloons of mixing oxygenolysis in sintering process to form 10-100 ��m of random spherical hole, utilize etching process to obtain the method in irregular hole, tens nanometer surface, finally obtain having the biomimetic artificial bone of the three-dimensional multistage pore structure similar with nature bone, laser spot diameter is micro-meter scale, and key step comprises:

(1) raw material preparation: add a certain amount of high polymer micro balloons in nano-bioactive ceramic powder, mixed uniformly powder is obtained by mechanical mixing, wherein superpolymer comprises poly(lactic acid) (PLA), polyglycolic acid (PGA), Poly(D,L-lactide-co-glycolide (PLGA) 3 kinds, and the massfraction of superpolymer is 10-40%;

(2) green compact are shaping: uniform laying one layer of mixed powder on sintering platform, powder layer thickness is 0.15-0.2mm, selectively scanning sintered powder according to support two-dimensional section information Control laser beam, by being layering, technology obtains three-dimensional bionic artificial bone scaffold green compact;

(3) clear powder process: sintering platform declines certain height, and after utilizing hairbrush, compressor, air gun or suction cleaner to remove unsintered powder, the gradient obtaining 150-800 ��m runs through hole;

(4) high temperature sintering: the green compact after clear powder are seated in temperature controlling stove and sinter again, and the removal carrying out superpolymer by precise hard_drawn tuhes furnace temperature curve forms the random spherical hole of 10-100 ��m simultaneously;

(5) acid and alkali corrosion: be immersed in by biomimetic artificial bone support in certain density acidity or basic solution and carry out chemical corrosion, takes out support after certain time, utilizes deionized water rinsing and dry, and obtains the surperficial irregular hole of tens nanometer.