CN1268583C - Porous bioceramic with controllable microstructure, its preparation method and application - Google Patents
Porous bioceramic with controllable microstructure, its preparation method and application Download PDFInfo
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- CN1268583C CN1268583C CN 02153079 CN02153079A CN1268583C CN 1268583 C CN1268583 C CN 1268583C CN 02153079 CN02153079 CN 02153079 CN 02153079 A CN02153079 A CN 02153079A CN 1268583 C CN1268583 C CN 1268583C
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Abstract
The invention relates to a porous bioceramic with a controllable microstructure, which is characterized in that the total porosity of the porous ceramic is 70% +/-15%, wherein the content of spherical pores exceeds 80% of the total porosity, the rest are micropores (the pore diameter is less than 10 micrometers), the diameter of the spherical pores is 100-1000 micrometers, the connection diameter between pores is controlled to be 10-700 micrometers, and the ratio of the connection diameter in the pores to the pore diameter of the spherical pores is 0.1-0.7. The invention also relates to a preparation method of the porous bioceramic and application of the porous bioceramic in the field of biomedicine.
Description
Technical field
The present invention relates to a kind of new ceramic material, be specifically related to a kind of porous bio-ceramic of controlled microstructure, the preparation method of this porous bio-ceramic, and the application in biomedical sector.
Background technology
Biological ceramics has the history of eight more than ten years.Just used tricalcium phosphate to carry out experimentation on animals as far back as nineteen twenty Albee doctor, the result shows that osseous tissue and material have good consistency.But because at that time in the manufacture craft of material, all many-sides such as evaluation of its biocompatibility have certain shortcoming, so do not paid attention to by people in the quite a long time.Until early seventies, doctor Hench has found the utility value of excellent compatibility in medical field of biological ceramics, and the research in this field just becomes increasingly active.
The microstructure of porous bio-ceramic mainly comprises the interior connection in hole, hole and void content etc., these structural parameter differences, and the biological effect that causes is also different.Studies show that micropore (＜10 microns) directly influences the degraded of material, the interior connection in hole, hole and void content be the directly growth of influence tissue then.What of the shape in hole and void content have directly related property to the mechanical strength of material.More result of study shows: contain void content 50% for good, the aperture is suitable for the formation of osseous tissue for the 100-300 micron.It is widely different that but many results of study show, its major cause is to have ignored the effect that connects in the hole.
At present the making of porous bio-ceramic is commonly used four kinds of methods: (1) utilizes natural porous microstructure material (as corallite etc.), and chemical treatment and/or sintering form porous ceramics under hyperbaric environment.(2) prepare slurries with ceramic powder, add whipping agent (as hydrogen peroxide etc.) and make the slurries foaming, drying is shaped and sintering forms porous ceramics.(3) mix mutually by certain ratio row with filling bracket thing (particles such as sugar, paraffin, camphor) with ceramic powder, make its press molding.Eliminate stent material through the gasification of heating, at high temperature sintering forms porous ceramics then.(4) be mixed with slurries with ceramic powder, be filled in the plastic foam sponge, make its dry forming.Eliminate stent material through the gasification of heating, at high temperature sintering forms porous ceramics then.For example International Patent Application WO 9834654 discloses a kind of application warming portion molten plastic, and the bond plastic particle by controlled temperature and time, is controlled the size of particle bounding point; International Patent Application WO 95/21053 is to be applied in pressurization in the mould, makes to form point of contact between plastic grain; U.S. Pat 5,549,123 are to use raw material powder and plastic grain mixture through press molding, do not have the method for any control particle contact size.
But the ceramic product of aforesaid method production exists such-and-such shortcoming,, heterogeneity irregular as hole shape; The void content of pottery is low; Connect the footpath in the hole of pottery and be difficult to the control making, cause the low or interior connection of hole ditch passband footpath too little; When ceramic void content surpassed 50%, mechanical property was just very poor; The one-tenth of ceramic product is grouped into purity and is difficult to control; Weak points such as the bulk product surface smoothness is not good enough.They can directly influence ceramic biological effect and material degradation degree, and influence the clinical of material and install and use.
Summary of the invention
In view of this, one object of the present invention is to provide a kind of porous bio-ceramic with may command microstructure, and it has unique internal microcellular structure, as connecting the size in footpath, the shape in hole etc. in aperture, the hole.
Another object of the present invention is to provide a kind of method for preparing above-mentioned porous bio-ceramic, this method accuracy height, favorable repeatability can be controlled according to the needs of human organ and tissue growth, to produce corresponding fine structure material.
Another purpose of the present invention is to provide the application of above-mentioned porous bio-ceramic in biomedical sector, in particular for the repair and reconstruction of organ and tissue defect, and the application in orthopaedics, ophthalmology, Plastic Surgery and Stomatological Department etc.
The inventor passes through the research to the structure and the performance of porous ceramics, and the size in connection footpath and density have tangible influence to the growth of osseous tissue in the hole of discovery porous ceramics, thereby have proposed a kind of novel porous pottery with unique texture.
According to porous ceramics of the present invention, the total porosity that it is characterized in that this porous ceramics is 70% ± 15%, wherein the content of spherical pore surpasses 80% of total porosity, residue is micropore (aperture＜10 micron), the diameter of spherical pore is the 100-1000 micron, connect the footpath in the Kong Yukong and be controlled in the 10-700 micron, the connection footpath is 0.1-0.7 with the ratio in aperture, ball hole in the hole, as shown in Figure 1.Fig. 1 has represented for porous bio-ceramic to form the possibility that connects the footpath in the hole when the aperture, different balls hole intuitively, and wherein dash area is for forming the connection zone directly hole in.
In the present invention, the interior connection in hole is the passage of communicating with each other between finger-hole and the hole, connects the diameter that the footpath is meant this passage in the hole, and its size can Be Controlled be made fully.Can observe by scanning electronic microscope, each spherical pore has to connect in 1-8 links up mutually with adjacent hole.Connect footpath Chang Youxuan Be Controlled in the above-mentioned hole and be produced on the 100-300 micron.Since have so pore structure, especially controlled interior connection footpath, and the void content of the feasible porous ceramics that obtains reaches 70% ± 15%, also can be suitable for the formation of osseous tissue.
Connecting in the hole is the door or the passage in hole in the material, and its size directly affects the biological characteristics (formation of tissue and growth) of material.Its biological function is that cell can be entered among the hole, and by the blood supply vegetative cell, it can be survived and breed, and formative tissue.But, be formed with the tissue of good function, enough blood supplies must be arranged; Here the size that connects in the hole plays decisive role.It has been generally acknowledged that to connect the footpath in the hole of porous ceramics big more, blood supply is sufficient more.But a little less than connecting the footpath in the excessive hole and material being become be highly brittle, can not reach good blood confession and connect the footpath in too small the hole in, make newborn tissue form function corresponding, so it is directly of crucial importance to control in the hole connection well.But prior art is difficult to reach the requirement that the interior connection footpath of porous ceramics is controlled, and the present invention has made its contribution at this.
The diameter of the spherical pore of porous ceramic film material of the present invention is controlled in the 100-1000 micron, preferably at the 200-700 micron; The interior footpath that connects is controlled in the 10-700 micron, preferably at the 100-300 micron, to satisfy the needs of cell and tissue growth.
According to porous ceramics of the present invention, its hole shape is a globosity, even air hole distribution, and hole wall is smooth, and the difference of male and fomale(M﹠F) is the 0.2-1 micron.According to porous ceramics of the present invention, it both can be made as the aperture unanimity, also can be made as big aperture phase blended product.
The surface condition of porous ceramics of the present invention and internal microstructure can be clearly illustrated by scanning electron microscope, shown in Fig. 2 and 3.Can carry out qualitative and quantitative assay to the situation that is connected the footpath in the hole of the surface of sample and fracture and the hole by scanning electron microscope simultaneously.In addition, porous ceramics of the present invention can be selected different moulds for use according to shape, the dimensions of desired product, for example makes sphere, cube, cylindrical, wedge, particle shape etc., as shown in Figure 4.
The invention provides a kind of preparation method of porous ceramics, it comprises by chemical process and is partly dissolved spherical plastic particles, makes its bonding formation porous framework thing, and the long-pending variation of service recorder instrument control framework object, come the size of the bonding millet cake of strict control particle, promptly with the interior connection of metapore.In the framework thing, pour into the ceramic powder slurries of preparation subsequently, dry forming, the framework thing is eliminated in heating gasification, and high temperature sintering forms porous ceramics.
Particularly, the preparation method of stupalith of the present invention comprises following step:
(1) selecting particle diameter is the plastics spheroidal particle of 100-1200 micron;
(2) according to shape of product and size, make corresponding mould, this mould is divided into two portions: first part is the mould hollow body, and another part is that mould is fastened body, and both fully accurately mate;
(3) selected plastics spheroidal particle is placed in the mould hollow body, and adds organic solvent, make particle be partly dissolved step by step, set up mould simultaneously and fasten body, body sinking degree is fastened in monitoring, when reaching predetermined parameters, remove organic solvent and stop dissolving, obtain porous framework thing;
(4) perfusion ceramic powder slurries in the framework thing make its dry forming, remove the drying of ceramic powder of framework beyond the region of objective existence Zhou Duoyu;
(5) will pour into dried framework thing and be placed in the vapourizing furnace, progressively heating makes the organic substance elimination of being gasified;
(6) product after will gasifying moves in the high temperature sintering furnace, progressively is warmed between 800-1400 ℃, makes it sinter porous ceramics into.
In the method for the invention, but service regulations and irregular spherical plastic particles.Be meant complete sphere at this term " regular spherical ", as glass sphere, and correspondingly, term " irregular sphere " then is meant the class sphere.In principle, can be by organic solvent dissolution, nontoxic plastic grain all can be used for the present invention as the pore-creating material, but preferred plastic grain is selected from polystyrene, polyethylene, polypropylene, polyvinyl chloride, polymeric amide and polymethylmethacrylate etc., it does not stay any objectionable impurities behind high temperature sintering, also not with body material generation chemical reaction.Organic solvent used in the preparation process of porous ceramics of the present invention is for slowly dissolving the solvent of described plastic grain gradually, it is according to the difference of the plastic grain selected for use and difference is preferably used as acetone, diacetone, bromochloromethane, hexone, chloroform etc.
In the method for the invention, the material of mould therefor is had no particular limits, can use used solvent is chemically inert material constitutes, for example stainless steel, pottery, glass, gypsum etc.
In the method for the invention, the registering instrument that the monitoring of the sinking degree of mould key preferably will link to each other with transmitter owing to the input of the process of dissolution with solvents plastic grain by transmitter is controlled the structure of porous framework thing thus.The transmitter that uses can be for example machinery, electronics, the photoelectricity subclass transmitter that can be used for described purposes.
In the step (3) of the inventive method, described preset parameter is continuously measurable, and its structure with final porous bio-ceramic is closely related.When this preset parameter reached certain value, just control stopped the sinking that mould is fastened body.
Particularly, describe the calculating and the control of described preset parameter in detail in conjunction with Fig. 5 and Fig. 6 and following formula.Fig. 5 is for showing the contraction situation synoptic diagram in the porous bio-ceramic making processes of the present invention, wherein Δ
OrgBe the shrinkage (μ m) of plastics spheroidal particle framework thing, Δ
FriBe the shrinking percentage (%) of pottery in sintering; Fig. 6 is the graph of a relation that connects footpath and the relation conefficient of spherical pore in the indication window, by this figure inventor summed up be used for described preset parameter control about the interior definite experimental formula that is connected big or small b directly under natural accumulation situation in theoretical that coefficient a and plastics spheroidal particle can form that instructs that concerns between footpath and the shrinkage that connects.
Δ
org＝(x×h)/[(1-Δ
fri)×(1-x)]，
X=(di-b)/100 * a wherein,
a＝(4.7329dp-0.0015dp
2-453.31)/100
b＝0.0001dp
2+0.0718dp+24.636
In the formula: Δ
Org: the shrinkage (μ m) of plastics spheroidal particle framework thing,
Δ f
Ri: the shrinking percentage (%) of pottery in sintering,
A: what concern between interior connection footpath and the shrinkage instructs coefficient,
B: under the situation that the plastics spheroidal particle is piled up naturally, the interior connection footpath (μ m) that can form in theory,
Di: the interior connection footpath (μ m) of ceramic endoporus,
Dp: Ceramic Balls aperture (μ m),
H: the finished product height (μ m),
X: the relation conefficient that connects footpath and ball aperture in the hole.
By setting and the control to above preset parameter, the method according to this invention can obtain to have the porous ceramics of desired structure.In this process, selected usually granular size is exactly the size in following hole; Grain amount is exactly following void content; The size of plastic grain dissolving back bounding point is exactly the size that connects in the following hole.
In the method for the invention, type to used ceramic powder stock has no particular limits, all can use as long as can satisfy the ceramic powder of biocompatibility requirement, for example the mixture of hydroxyapatite, tricalcium phosphate, hydroxyapatite and tricalcium phosphate or aluminum oxide etc.The slurries of described ceramic powder are the slurries that itself and water form.
In the step (5) of the inventive method, the treatment temp of framework thing after the perfusion and time gasified to eliminate with organic substance to be as the criterion, and usually treatment temp is controlled at more than 200 ℃, keeps 12-48 hour.After being eliminated fully as organic material, product returns to the original color of ceramic powder.
In the method for the invention, processing parameter has good operability, and those skilled in the art can carry out the setting of processing parameter and the control of technological process according to following principle:
1) making of die size size adds that according to the product size gross shrinkage in the ceramic making determines.
2) the ball hole makes the spherical particulate screening of required corresponding plastics, adds that according to the ball hole size shrinkage of pottery in sintering process determine.
3) connecting making directly in the hole is that the size of controlling the particle bounding point obtains according to the measurement of the long-pending shrinkage degree of framework object.Its mechanism always ball occurs and contacts with the point-like of ball for when a plurality of plastic sphere puts together.When plastics were progressively dissolved by organic solvent, the size of spheroid point of contact will progressively increase, and the gap between spheroid can progressively dwindle, and their cumulative volume amount of while is dwindled more obvious, and this cumulative volume reduction volume can be measured and record by the potential difference instrument.
4) control of porous ceramics product size size and volume according to the shrinking percentage in the different ceramic raw material sintering processes (is 10-20% as pure ha or pure phosphoric acid DFP), in making processes, adds that with the product size this shrinkage determines.
The advantage of porous ceramics of the present invention is: (1) can pass through the mould once-forming, makes multiple shape and size product; In the production process, do not need cutting and pruning, can not cause the pollution of product; Product surface is very bright and clean, and visible hole is linked up mutually with the external world.(2) hole shape is a globosity, even air hole distribution, and hole wall is smooth, and the mechanical property of product obviously increases.(3) total porosity reaches 70% ± 15%, and wherein spherical pore accounts for more than 80% of total amount, remains to be micropore.(4) the diameter Chang Youxuan of spherical pore is controlled in the 200-700 micron, and this spherical pore fully can be according to different purposes, and Be Controlled is made, and each spherical pore has and is connected in adjacent hole in 1-8 and links up mutually.(5) connect footpath Chang Youxuan in the described hole and be controlled in the 100-300 micron, and can reach connect directly in the hole in and the ratio in aperture, ball hole between 0.1-0.7.
Experimental results show that the porous ceramics with above-mentioned microstructure features has extremely important using value in biomedical sector.They can be controlled fully and be made into the microstructure products that is fit to human organ and tissue growth needs.Play the filling and the supporting role of organ and tissue, and the conduction of cell and tissue can be arranged, to be used for the repair and reconstruction of organ and tissue defect.Porous bio-ceramic of the present invention can be widely used in biomedical sectors such as orthopaedics, ophthalmology, Plastic Surgery, Stomatological Department, also can be used as tissue engineering bracket.
For understanding above-mentioned and other advantage and feature of the present invention more, below by non-restrictive example and the present invention will be further elaborated in conjunction with the accompanying drawings.
Brief Description Of Drawings
Fig. 1 be porous bio-ceramic when aperture, different balls hole, form the graph of a relation that connects possibility directly in the hole;
Fig. 2 is the surface micro-structure aspect graph of the porous ceramics product of the present invention observed under scanning electron microscope;
Fig. 3 is the section microstructure form figure of the porous ceramics product of the present invention observed under scanning electron microscope;
Fig. 4 is the profile synoptic diagram of the portioned product of porous ceramics of the present invention;
Fig. 5 is for showing the synoptic diagram of the contraction situation in the porous ceramics making processes of the present invention;
Fig. 6 is the graph of a relation of connection footpath in the hole of porous ceramics of the present invention with the relation conefficient in aperture, ball hole;
Fig. 7 is the sem photograph of the interior connection of the porous ceramics of the demonstration embodiment of the invention 1;
Fig. 8 is the sem photograph of the interior connection of the porous ceramics of the demonstration embodiment of the invention 3;
Fig. 9 is the sem photograph of the interior connection of the porous ceramics of the demonstration embodiment of the invention 4.
Embodiment
Embodiment 1:
Making is a raw material with the pure ha ceramic powder, 20 millimeters of diameters of preparation and high 40 millimeters right cylinder product.The requirement of product microstructure be 500 ± 50 microns of void content 70% ± 5%, aperture with the hole in be connected 100 ± 20 microns in footpath.Concrete steps are as follows:
1) sieve of use standard model, filtering out diameter is the plastics spheroidal particle of 500-600 micron;
2) preparation has the stainless steel mould of 22.73 millimeters of diameters and high 80 millimeters cylindrical cavities;
3) ceramic powder is mixed with the slurries of 70% concentration with distilled water;
4) particle with 13 grammes per square metres is placed in the mold cavity, adds 10 milliliters organic solvent; Set up mould and fasten body, connect transmitter and registering instrument; Fasten body when sinking to 240 microns when showing to look, remove organic solvent and stop dissolving; Can obtain porous framework thing this moment;
5) perfusion ceramic powder slurries in the framework thing make its dry forming, remove the drying of ceramic powder of framework beyond the region of objective existence Zhou Duoyu;
6) will pour into dried framework thing and be placed in the vapourizing furnace, progressively heat, continue 24 hours, make the organic substance elimination of being gasified to more than 200 ℃.Formed ditch general character vesicular structure this moment in material;
7) product after will gasifying moves in the high temperature sintering furnace, progressively is warmed to 1250 ℃ and continues 10 hours, makes it sinter porous ceramics into.
The electromicroscopic photograph of gained porous ceramics as shown in Figure 7.
Embodiment 2
Except that used raw material is that bata-tricalcium phosphate ceramic powder and sintering temperature are 1100 ℃, the control of other processing parameter and product structure is identical with embodiment 1.
Embodiment 3:
Connecting the footpath in the hole is 210 ± 50 microns, and the requirement of all product compositions, form, size and microstructure is analogous to embodiment 1.
In operation steps the 1st), 2), 3), 5), 6) and 7) step all is same as embodiment 1, only the 4th) in the step, the particle of 14 grammes per square metres is placed in the mold cavity, and changes processing parameter, it is 3750 microns that mould is fastened the body deflection, can obtain required microstructure (Fig. 8).
Embodiment 4:
This embodiment adopts ordinary method to prepare porous ceramics, compares with the product with the inventive method preparation.
With the pure ha ceramic powder is raw material, 20 millimeters of diameters of preparation and high 40 millimeters right cylinder product.The product microstructure is 50% void content and 200-300 micron pore size.
Concrete steps are as follows:
1) sieve of use standard model, filtering out diameter is the irregular shape particle of camphor of 200-300 micron;
2) ceramic powder with 67 grammes per square metres mixed in stirrer 2 hours with 33 grammes per square metre camphor particles;
3) mixture is circulated into rubber model specifically in, and be placed into after sealing and under the pressure of 300-320MPa, pressurize in the pressing machine, continue 5 minutes, make its shaping;
The piece shape mixture that 4) will be shaped is placed in the vapourizing furnace, progressively heats to more than 50 ℃, keeps 8 hours, makes the elimination (this moment in material, constituted vesicular structure) that is gasified totally of camphor particle;
5) product after will gasifying moves in the high temperature sintering furnace, progressively is warmed to 1270 ℃, continues 10 hours, just sinters porous ceramics into;
6) porous ceramics that sinters is used cutting method, produce required right cylinder product.
The stereoscan photograph of gained porous ceramics as shown in Figure 9, irregular, the heterogeneity of hole shape wherein; Pore ditch passband is very low, connects in the rarely found foraminous.In addition, the contriver contrasts the porous ceramics of embodiment 1 and the porous ceramics of this Comparative Examples, and the result is as shown in table 1 below.
Table 1
| Technical indicator | Unit | Embodiment 1 | Embodiment 4 | |
| Void content | ％ | 70±15 | ＜60 | |
| The | Micron | 500±50 | 200-300 | |
| Hole shape | The homogeneous sphere | Irregular shape | ||
| Connect the footpath in the hole | Controlled fully | Uncontrollable | ||
| Pore ditch passband | Link up fully | Link up rate variance | ||
| The surface condition of product | Bright and clean | Coarse | ||
| Concavo-convex poor of ball hole wall | Micron | 0.2-1.0 | ＞1.0 | |
| Mechanical strength | MPa | 5-25 | 2-10 | |
| Material degradation | Controlled fully | Uncontrollable | ||
| Tissue is grown into | Center until sample | Only at the periphery of sample |
Embodiment 5:
In the biological effect research of porous ceramics microstructure of the present invention, to adopt aperture, ball hole be the 200-260 micron with four kinds of different holes in be connected the directly hydroxyapatite porous ceramics right cylinder of (30,60,100 and 130 microns), it is planted respectively in the spongy bone of rabbit.Organize quantitative analysis skeletonization amount to show after 12 weeks: the porous ceramics that connects the footpath in 130 microns be connect in 68%, 100 micron the footpath be connect in 55%, 60 micron the footpath be 50% with 30 microns in to be connected the footpath be＜40%.This result of study has confirmed to connect in the hole footpath and has played a part extremely to want in biological effect.
Embodiment 6:
The purpose of present embodiment is to understand hydroxyapatite porous bio-ceramic of the present invention (550 ± 100 microns of void content 75% ± 10%, aperture with hole in be connected 130 ± 30 microns in footpath) doping bone marrow stem cell (10
7Cells/ml) the osteanagenesis potentiality after, and compare with porous ceramics product that traditional technology is produced.Behind 13 millimeters of diameters and high 3 millimeters discoid biological ceramics body doping bone marrow stem cell, it is planted in the rabbit muscle of back.The back Histological research discovery bone marrow stem cell induced osteogenesis effect of 4 weeks, this porous ceramics obviously is better than the porous ceramics that traditional technology is produced, skeletonization at the traditional technology porous ceramics only limits to first and second round of periphery, and in porous ceramics of the present invention, can both find the skeletonization phenomenon in all ball holes, statistical procedures has significant difference (p＜0.05), and good vascularization is arranged.
Embodiment 7:
Bata-tricalcium phosphate porous bio-ceramic of the present invention (550 ± 100 microns of void content 75% ± 10%, aperture with hole in be connected 130 ± 30 microns in footpath) is processed into disk shape (13 millimeters of diameters and high 3 millimeters), doping rabbit articular chondrocytes (2 * 10
7Cells/ml), cell-ceramic composite is placed in the rotating biological reactor cultivate subsequently, cultivated for 1 week after, it is subcutaneous that it is transplanted to the nude mice back.Body is implanted into the postoperative specimen sampling in 4,8,16 weeks, carries out Histological research.Its result shows that the plantation back begins to have cartilage formation 4 weeks and material degradation is arranged, and in time prolongation cartilage amount and material degradation amount increase gradually.The ceramic hole in 8 week backs is filled by cartilage fully, and the phenomenon of visible enchondral ossification.Originally the structure that studies show that porous bio-ceramic of the present invention is suitable as cartilage frame, and is fit to be applied to clinical.
Embodiment 8:
With bata-tricalcium phosphate porous bio-ceramic product of the present invention (550 ± 100 microns of void content 75% ± 10%, aperture with hole in be connected 130 ± 30 microns in footpath) comparing property orthopaedics clinical application research.Actual selected patient is 139 examples, and 50 examples are for using this ceramic product, and 50 examples are autologous bone transplanting, and 39 examples are other biomaterial of calcium and phosphor.Sick plant fracture is arranged, nonunion, bone are damaged, bone tumor etc.Follow-up time is 1 year.Clinical application method be above-mentioned materials is inserted be embedded into that bone lacks in the chamber or between, or be implanted in fracture and nonunion around, make it play bone conduction effect.Its as a result the experimental group of display application ceramic product of the present invention find no infection, inflammation, allergy and rejection, material appears in 84% case after three months bony union, and material degradation phenomenon is gradually arranged, clinical effectiveness is analogous to autologous bone transplanting.But the autologous bone transplanting experimental group is got bony site pain and operating time continues longer.The case of other calcium phosphate material experimental group 60% does not have bony union, and has two cases inflammatory reaction and material rejection to occur.
Embodiment 9:
With hydroxyapatite porous bio-ceramic eye holder product of the present invention (550 ± 100 microns of void content 75% ± 10%, aperture with hole in be connected 130 ± 30 microns in footpath, product diameter 16-22 millimeter) clinical application in 30 routine patients.Patient is because row eyeball excise postoperatives such as wound, perforated ulcer, tumour need carry out filling and support in the socket of the eye.Because this product biological degradation is extremely faint, approach not degrade, and biocompatibility is fine, therefore can retain in vivo for a long time, reach the support effect.After eyeball is partially or completely extractd, eye holder is implanted in the socket of the eye, and intraocular flesh can be fixed on the surface, among tissue and blood vessel are grown into eye holder subsequently, reach intraocular flesh biological being permanently fixed on eye holder simultaneously.After ocular prosthesis is installed, reach beautification function.Find no infection, inflammation, allergy and rejection in the application result, postoperative was observed in 3 months, and the interior vascularization of this group of products implant is obvious, consulted reported literature statistics over nearly 10 years, and homemade hydroxyl-apatite-artificial eye table extrusion rate is 8%; Import corallite eye holder extrusion rate is 6%; And an example does not take place in this group, and (, muscle tissue normal with muscle function in the eye socket grow into implant and vascularization relevant) is joined 15 ° rotating function is arranged about level behind the eye holder to peace.
Claims (10)
1, a kind of porous bio-ceramic of controlled microstructure, the total porosity that it is characterized in that this porous ceramics is 70% ± 15%, the content of spherical pore surpasses 80% of total porosity, the diameter of spherical pore is the 100-1000 micron, connecting the footpath in the Kong Yukong is the 10-700 micron, and the connection footpath is 0.1-0.7 with the ratio in aperture, ball hole in the hole.
2, according to the porous bio-ceramic of claim 1, the diameter that it is characterized in that described spherical pore is the 200-700 micron.
3,, it is characterized in that connecting in the described hole footpath and be the 100-300 micron according to the porous bio-ceramic of claim 1.
4,, it is characterized in that described each spherical pore has 1-8 interior the connection to link up mutually with adjacent hole according to the porous bio-ceramic of claim 1.
5, according to the porous bio-ceramic of claim 1, it is characterized in that the hole wall of described spherical pore is smooth, the concavo-convex difference of wall surface of the hole is the 0.2-1.0 micron.
6, a kind of method for preparing each porous bio-ceramic in the claim 1 to 5, it may further comprise the steps:
(1) selecting particle diameter is the plastics spheroidal particle of 100-1200 micron;
(2) according to shape of product and dimensions size, make corresponding mould, this mould is divided into two portions: first part is the mould hollow body, and part is fastened body for mould in addition, and both fully accurately mate;
(3) selected plastics spheroidal particle is placed in the mould hollow body, and adds organic solvent, make particle be partly dissolved step by step, set up mould simultaneously and fasten body, body sinking degree is fastened in monitoring, when reaching preset parameter, remove organic solvent and stop dissolving, obtain porous framework thing;
(4) perfusion ceramic powder slurries in the framework thing make its dry forming;
(5) will pour into dried framework thing and be placed in the vapourizing furnace, progressively heating makes the organic substance elimination of being gasified;
(6) product after will gasifying moves in the high temperature sintering furnace, progressively is warmed between 800-1400 ℃, makes it sinter porous ceramics into;
Wherein said preset parameter is determined by following formula:
Δ
org＝(x×h)/[(1-Δ
fri)×(1-x)]，
X=(di-b)/100 * a wherein,
a＝(4.7329dp-0.0015dp
2-453.31)/100
b＝0.0001dp
2+0.0718dp+24.636
In the formula: Δ
Org: the shrinkage of plastics spheroidal particle framework thing, μ m,
Δ
Fri: the shrinking percentage of pottery in sintering, %,
A: what concern between interior connection footpath and the shrinkage instructs coefficient,
B: under the situation that the plastics spheroidal particle is piled up naturally, the interior connection footpath that can form in theory, μ m,
Di: the interior connection footpath of ceramic endoporus, μ m,
Dp: the Ceramic Balls aperture, μ m,
H: the finished product height, μ m,
X: the relation conefficient that connects footpath and aperture, ball hole in the hole.
7,, it is characterized in that described plastic grain is selected from polystyrene, polyethylene, polypropylene, polyvinyl chloride, polymeric amide or polymethylmethacrylate according to the method for claim 6.
8,, it is characterized in that described ceramic raw material is the mixture or the aluminum oxide of hydroxyapatite, tricalcium phosphate, hydroxyapatite and tricalcium phosphate according to the method for claim 6.
9, according to the method for claim 6, it is characterized in that in step (5), with the framework thing after the perfusion under greater than 200 ℃ temperature, gasification process 12-48 hour.
10, each porous bio-ceramic is used for the application of the repair and reconstruction of organ and tissue defect in the claim 1 to 5 in orthopaedics, ophthalmology, Plastic Surgery, Stomatological Department.
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| CN100536802C (en) * | 2006-12-29 | 2009-09-09 | 西安交通大学 | Dual-scale micro-structure artificial bone scaffold and preparation method thereof |
| CN101148360B (en) * | 2007-08-14 | 2010-05-19 | 西安交通大学 | A customized molding method for gradient porous structure ceramics |
| CN107312707B (en) * | 2017-08-17 | 2020-05-19 | 卢建熙 | Mesenchymal stem cell collecting device and method |
| CN110078493B (en) * | 2019-05-28 | 2022-02-22 | 上海贝奥路生物材料有限公司 | Method for preparing ceramic microspheres by template method |
| CN110882417B (en) * | 2019-12-20 | 2021-02-19 | 上海贝奥路生物材料有限公司 | Metal prosthesis of composite porous bioceramic and preparation method thereof |
| CN115959928B (en) * | 2023-02-02 | 2024-01-26 | 卢建熙 | A porous bioceramic rod for functional reconstruction of femoral head necrosis and its preparation method and application |
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