CN101698115A - Composite tissue engineering scaffold material with anti-infection property and manufacturing method thereof - Google Patents
Composite tissue engineering scaffold material with anti-infection property and manufacturing method thereof Download PDFInfo
- Publication number
- CN101698115A CN101698115A CN200910112757A CN200910112757A CN101698115A CN 101698115 A CN101698115 A CN 101698115A CN 200910112757 A CN200910112757 A CN 200910112757A CN 200910112757 A CN200910112757 A CN 200910112757A CN 101698115 A CN101698115 A CN 101698115A
- Authority
- CN
- China
- Prior art keywords
- gelatin
- solution
- antibiotic
- gel
- preparation
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Images
Landscapes
- Materials For Medical Uses (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention relates to a composite tissue engineering scaffold material with anti-infection property and a manufacturing method thereof, in particular to a tissue engineering scaffold material. The invention provides the composite tissue engineering scaffold material with the anti-infection property and the manufacturing method thereof. The composite tissue engineering scaffold material is antibiotic microsphere-gelatin-oxosilane three-dimensional porous tissue engineering scaffold material which is formed by compounding the antibiotic microsphere, the gelatin, 3-(2,3-glycidoxypropyl) propyl trimethoxysilane and calcium salt. The freeze-dried antibiotic microsphere is dispersed into acid solution and then added with the gelatin solution to be dissolved to obtain solution A; the solution A is added with the calcium salt to obtain solution B, and GPSM is added into the solution B to be mixed together to obtain solution C; the solution C is injected into a mould, and microsphere-gelatin-oxosilane gel can be obtained by sol-gel; ammonia water solution is injected into the mould filled with the microsphere-gelatin-oxosilane gel for soaking gel, demoulding and washing; and the microsphere-gelatin-oxosilane gel is treated by freezing-freeze-drying method, and the product can be obtained after freeze-drying.
Description
Technical field
The present invention relates to a kind of tissue engineering bracket material, especially relate to a kind of composite organization engineering stent material by using and preparation method thereof with anti-infection property.
Background technology
Since 19th century, bone grafting is devoted to repair always because wound, tumor, bone on a large scale that infection caused are damaged, to recover limb function.But there are many problems in this method, as the shortage of immunologic rejection and donor tissue and organ.The target of tissue-engineered bone is that to utilize stem cell or osteoblast and biologic bracket material to carry out compound, thereby the osseous tissue that disease is decreased can be repaired and regenerate.Timbering material can be used as the carrier of signaling molecule or cell on the one hand, and it is transported to defect location, also is the necessary substrate of new bone growth on the other hand.
Good timbering material should have excellent biological compatibility and function reparation property, has absorbability simultaneously.Be characterized in corresponding to the dynamic (dynamical) controlled degraded and absorbed rate of tissue reconstruction.The physico-chemical property of material surface as wettability, surface free energy, electric charge and pattern, should be adjusted to and is suitable for cell adhesion, propagation, differentiation.In addition, timbering material also should have the mechanics parameter and the high porosity of the natural bone tissue of being similar to as the substrate of new bone growth.Bone tissue engineering stent material mostly is polymer greatly at present, as L-polylactic acid (L-polylactic acid, PLA), polyglycolic acid (polyglycolic acid, PGA) and copolymer etc., the back degraded is slow but it implants, and immunological rejection is arranged with surrounding tissue, can cause lymphocytic infiltration and engulf reaction.Another kind of timbering material is a bioceramic, as hydroxyapatite (hydroxyapatite, HA), tricalcium phosphate (tricalcium phosphate, TCP), the hydroxyapatite that transforms of Ca-P ceramic (HA/TCP) and Corallium Japonicum Kishinouye (coralhydroxyapatite, CHA) etc.But this class fatigue of materials intensity is lower, and rigidity and fragility are higher, and porosity is low, is difficult to processing.
Application number is that 200410094895.6 Chinese invention patent application discloses a kind of three-dimensional porous tissue engineering bracket material that adopts sol-gel process and freeze-drying preparation, prepared support has good biological activity and biological degradability, is suitable for reproducing of bone/cartilage tissue.But when above-mentioned timbering material being used for the damaged treatment of opening (or infectious) bone, because the residual of pathogenic bacterium arranged, may causing and infect and cause operative failure.Systemic administration methods such as general normal employing injection of antibiotics solve the problems referred to above.But systemic administration is difficult to reach effective antibiotic concentration in the damage part, and can cause serious adverse, so be difficult to play effective anti-infectious function.
Summary of the invention
Purpose of the present invention aims to provide a kind of composite organization engineering stent material by using with anti-infection property and preparation method thereof, can be used for the damaged treatment of open osseous tissue.
Composite organization engineering stent material by using with anti-infection property of the present invention is antibiotic microspheres-gelatin-siloxanes three-dimensional porous tissue engineering bracket material, by antibiotic microspheres, gelatin, 3-(2,3-epoxy third oxygen) propyl trimethoxy silicane (GPSM) and calcium salt are composited, each set of dispense is a gelatin 1 than by mass fraction, antibiotic microspheres 0.01～0.1,3-(2,3-epoxy third oxygen) propyl trimethoxy silicane 0.5～1.5, calcium salt 0.01～0.2.
Preparation method with composite organization engineering stent material by using of anti-infection property of the present invention may further comprise the steps:
1) freeze dried antibiotic microspheres is dispersed in the acid solution, adds gelatin then, obtain solution A after the dissolving;
2) in solution A, add calcium salt and obtain solution B;
3) in solution B, add GPSM, mix solution C;
4) solution C is injected mould,, get antibiotic microspheres-gelatin-silicone gel through sol-gel process;
5) inject ammonia spirit in the mould that antibiotic microspheres-gelatin-silicone gel is housed, soak gel, the demoulding is cleaned;
6) adopt freezing-lyophilization that antibiotic microspheres-gelatin-silicone gel is handled, obtain having the antibiotic microspheres-gelatin-siloxanes three-dimensional porous tissue engineering bracket material of different pore-size distributions after the lyophilizing.
In step 1), press mass ratio, antibiotic microspheres: gelatin is preferably (0.01～0.1): 1, and described acid is preferably at least a in acetic acid, formic acid, the hydrochloric acid etc., and the solid content of solution A is 5%～16.5%.
In step 2) in, press mass ratio, calcium salt: gelatin is preferably (0.01～0.2): 1; Described calcium salt is a soluble calcium salt, preferably is selected from lime nitrate, calcium sulfate or calcium chloride etc.
In step 3), press mass ratio, GPSM: gelatin is preferably (0.5～1.5): 1, and described blended temperature is preferably 40～60 ℃.
In step 4), the temperature of described sol-gel process is preferably 40～60 ℃.
In step 5), the concentration of described ammonia spirit is preferably 0.5～3M, and the temperature of described immersion gel is preferably 20～40 ℃, and the time of soaking gel is preferably 8～24h, and washed with de-ionized water is preferably used in described cleaning.
In step 6), described employing is freezing-lyophilization to antibiotic microspheres-gelatin-silicone gel handle preferably earlier-20～-80 ℃ freezing down, described freeze dried temperature is preferably-80～-200 ℃.
Can as required three-dimensional porous tissue engineering bracket material be cut into required form and size, package spare after the sterilization.
Described antibiotic microspheres is antibiotic-gelatin-silicone microsphere, and concrete preparation method is as follows:
6) the preparation gelatine content is 0.5%～1.5% acid solution; Described acid is at least a in formic acid, acetic acid, the hydrochloric acid etc.;
7) in the acid solution of gelatin, add 3-(2,3-epoxy third oxygen) propyl trimethoxy silicane, under 40～60 ℃ of temperature, stirred 3～5 days; The mass ratio of 3-(2,3-epoxy third oxygen) propyl trimethoxy silicane and gelatin is (0.5～1.5): 1;
8) by quality than antibiotic: gelatin be (0.1～2): 1 adding antibiotic, stirring and dissolving;
9) by quality than tween 80: gelatin be (0.5～5): 1 adds tween 80, stirs 10～20min, drips the metabisulfite solution of 20wt%, occurs opalescence until solution colour by colourless becoming, and stops dropping;
10) continue to stir 20～24h, obtain antibiotic-gelatin-silicone microsphere solution, clean the conventional lyophilizing in back and preserve.
The present invention carries out antibiotic sustained release microsphere and three-dimensional porous tissue engineering bracket material compound, when guaranteeing that integral material has good biological activity, biological degradability, for support provides anti-infection ability.The antibiotic sustained release microsphere makes the antibiotic concentration of timbering material implant site maintain certain level by the antibiotic release behavior, has promptly suppressed bacterial growth and can not cause damage to body again, thereby prevented the generation of infecting.The three-dimensional porous tissue engineering bracket material of prepared composite antibiotic sustained-release micro-spheres, pore diameter range is at 100～300 μ m, this timbering material can be used for the damaged reparation of bone, when supporting that osseous tissue is rebuild, improve the ability that body infects in the implant site opposing, increased safety and success rate that timbering material uses.
Description of drawings
Fig. 1 is the infrared spectrum of gentamycin sulfate, gelatin-silicone microsphere, gentamycin sulfate-gelatin-silicone microsphere.In Fig. 1, abscissa is wave number Wavenumber/cm
-1, vertical coordinate is absorbance Transmittance/%; Wherein curve a is a gentamycin sulfate, and curve b is gelatin-silicone microsphere, and curve c is gentamycin sulfate-gelatin-silicone microsphere.
Fig. 2 is the transmission electron microscope picture of antibiotic microspheres.In Fig. 2, scale is 500nm.
Fig. 3 is the release curve of antibiotic sustained release microsphere.In Fig. 3, abscissa is time T ime (hr), and vertical coordinate is drug release rate Drug Release (%).
Fig. 4 is the stereoscan photograph of antibiotic sustained release microsphere-gelatin-siloxanes three-dimensional porous tissue engineering bracket material.In Fig. 4, scale is 100 μ m.
Fig. 5 is the scanning electron microscope picture that timbering material soaked in simulated body fluid 4 days.In Fig. 5, scale is 10 μ m.
Fig. 6 is the inhibition zone lab diagram of timbering material.
Fig. 7 is rabbit headbone CT figure, a wherein, and b, c are implant frame material group, d, e, f are the blank group of not embedded material.The arrow position is the defect of skull zone.A, d are rabbit headbone CT figure before the art; B, e are 1 month rabbit headbone CT figure of postoperative; C, f are the rabbit headbone CT figure of postoperative after 5 months.
The specific embodiment
The invention will be further described below by embodiment.
1, preparation antibiotic sustained release microsphere
(GPSM) is crosslinked for propyl trimethoxy silicane to adopt the sedimentation method to utilize 3-(2,3-epoxy third oxygen), and sodium sulfate prepares the antibiotic-gelatin-silicone microsphere solution of size about 500nm as precipitant:
(1) with the dissolve with hydrochloric acid solution gelatin powder 0.2g of 20mL 0.1M, add 0.1g 3-(2,3-epoxy third oxygen) propyl trimethoxy silicane then, 40 ℃ are stirred 96h down;
(2) add gentamycin sulfate (GS) and tween 80 successively, gentamycin sulfate (GS)/gelatin is (mass ratio) 1/1;
(3) dropwise add the Na of 20wt%
2SO
4The about 9mL of solution by the transparent opalescence shape that becomes, and continue to stir 24h until solution, obtains gentamycin sulfate-gelatin-silicone microsphere solution;
(4) with the centrifugal 15min of microspheres solution, pure water cleans twice, and conventional lyophilizing obtains gentamycin sulfate-gelatin-silicone microsphere powder.
Characterize with infrared spectrum, as shown in Figure 1.3450cm in the infrared spectrum of gentamycin sulfate
-1There is a broad peak at the place, belongs to-stretching vibration of OH 1628cm
-1The peak at place should belong to-NH
2Bending vibration, the bending vibration peak of-NH appears at 1550cm
-1The place, the stretching vibration peak of C-O-C appears at 1124cm
-1With 1060cm
-1The place.These absworption peaks all are the characteristic absorption peaks of gentamycin sulfate.1637cm in the infrared spectrum of gelatin-silicone microsphere
-1The place is the stretching vibration peak of C=O, 1384cm
-1The place then is-CH
3The symmetrical stretching vibration absworption peak, these absworption peaks come from gelatin.1117cm
-1The stretching vibration absworption peak of the Si-O-Si at place then comes from GPSM.C-O-C has appearred in the infrared spectrum of gentamycin sulfate-gelatin-silicone microsphere in the gentamycin sulfate in 1124cm
-1The characteristic absorption peak at place and gelatin-silicone composite are in 1117cm
-1The characteristic absorption peak of the Si-O-Si of place.Gentamycin sulfate is described and gelatin-silicone microsphere good combination, forms complex.The result who the material that obtains is used transmission electron microscope analysis shows antibiotic microspheres diameter about 500nm (Fig. 2).
2, preparation gentamycin sulfate sustained-release micro-spheres-gelatin-siloxanes three-dimensional porous rack material
(1) with the acetic acid solution dissolving gentamycin sulfate sustained-release micro-spheres 0.1g of 20mL 1M, in above-mentioned solution, adds 2g gelatin, 40～60 ℃ of following stirring and dissolving;
(2) add lime nitrate and GPSM successively, wherein lime nitrate/gelatin is (mass ratio) 0.2/1; The GPSM/ gelatin is (mass ratio) 0.5/1;
(3) above-mentioned solution fully mixes 4h, to fully even (not having phase-splitting), pours into then in the mould of 5cm X 8cm, seals, and carries out sol gel reaction in 40 ℃ of calorstats, takes out behind the 24h, obtains gentamycin sulfate sustained-release micro-spheres-gelatin-silicone gel;
(4) the ammonia spirit 20mL of adding 1M in above-mentioned mould places 16h down at 40 ℃, and the demoulding uses distilled water flushing until neutrality then;
(5) gel after will handling is in-80 ℃ of precooling 72h, and-200 ℃ of following lyophilization 24h promptly obtain gentamycin sulfate sustained-release micro-spheres-gelatin-siloxanes three-dimensional porous rack material after the lyophilizing.
3, scanning electron microscope pattern phenetic analysis
To the material application scanning electronic microscope photos surface topography that obtains, pore morphology and pore size distribution, as Fig. 4, the three-dimensional porous tissue engineering bracket material pore size distribution that obtains is at 50～200 μ m, and being evenly distributed, being communicated with of hole can be observed the gentamycin sulfate sustained-release micro-spheres on the hole wall.
4, external release experiment
Gentamycin sulfate sustained-release micro-spheres-gelatin-siloxanes three-dimensional porous rack material is carried out external release experiment.The timbering material of getting 1 * 1cm size with the PBS buffer solution of 3ml pH 7.4 in 37 ℃ of immersions, respectively at 0.5h, 1h, 2h, 4h, 6h, 12h, 24h, 48h, 72h, 120h, 168h, 360h take out the soak test, and the soak that more renews.Soak takes out and is placed in the 50ml volumetric flask, add concentrated sulphuric acid 5.0ml, 100 ℃ of water-bath 30min, cooling adds water to about 40ml, puts cold, add water to again scale shake up put cold, do contrast after blank material soak is handled, measure absorption value at the 232.0nm place, record the concentration of gentamycin sulfate with ultraviolet.Fig. 3 is gentamycin sulfate sustained-release micro-spheres-gelatin-siloxanes three-dimensional porous rack material at 37 ℃, pH is drug release behavior in 7.40 the PBS medium.As seen from the figure, gentamycin sulfate is prominent releasing in 24h, killing bacteria in a large number, and after this rate of release is tending towards slowly, can keep stable release with lasting antibacterial.
5, biological activity test
The material that obtains is carried out biological activity test.The material of preparation is taken out 1cm
3The sample of volume size is immersed in the poly-PET bottle of the sealing that 20mL simulated body fluid (SBF solution) is housed, and 36.5 ℃ of constant temperature are placed, and takes out sample respectively at soaking after 1 day, 3 days, 7 days and 14 days, during every 48h with fresh SBF solution replacing soaking solution.After soak finishing, the sample that takes out with deionized water rinsing number time, is continued reaction to stop SBF and sample, under 37 ℃, dry then to constant weight.Then, adopt SEM to observe its surperficial pattern (Fig. 5), as can be seen, after gentamycin sulfate sustained-release micro-spheres-gelatin-siloxanes three-dimensional porous rack material soaks in simulated body fluid, hydroxyapatite is deposited on its surface, so this material has good biological activity.
6, zoopery
With rabbit with 3% pentobarbital sodium auricular vein injecting anesthetic, cut its skull outside skin, expose its skull face, and manufacture the breach that diameter is approximately 1cm with scalpel and mosquito forceps, gentamycin sulfate sustained-release micro-spheres-gelatin-siloxanes three-dimensional porous rack material is implanted its defect, another group is manufactured the breach that diameter is approximately 1cm with scalpel and mosquito forceps equally, but embedded material not, as the blank group.Respectively at postoperative one month and five months rabbit is used etherization, and be CT figure with the lightspeed64 of U.S. GE company row CT machine.The result is as shown in Figure 7: a, b, c are implant frame material group, and d, e, f are blank group (arrow indication place is the defect of skull place).A, d are rabbit headbone CT figure before the art; B, e are month rabbit headbone CT figure of postoperative; C, f are the rabbit headbone CT figure of postoperative after 5 months.The rabbit headbone healing of being schemed visible embedded material group by CT is effective than the blank group, illustrates that this kind timbering material can be used as the good timbering material that is applied to the bone tissue engineer reparation.
Embodiment 2
With the dissolve with hydrochloric acid solution gentamycin sulfate sustained-release micro-spheres 0.05g of 20mL 0.1M, in above-mentioned solution, add 2g gelatin, 60 ℃ of following stirring and dissolving.Add lime nitrate and GPSM more successively, wherein lime nitrate/gelatin is (mass ratio) 0.05/1; The GPSM/ gelatin is (mass ratio) 1/1.Above-mentioned solution fully mixes 2h, to fully even (not having phase-splitting), pours into then in the mould of 5cmX 8cm, seals, and carries out sol gel reaction in 40 ℃ of calorstats, takes out after 1 day, obtains gentamycin sulfate sustained-release micro-spheres-gelatin-silicone gel.The ammonia spirit 20mL that adds 1M in above-mentioned mould places 16h down at 40 ℃, uses distilled water flushing until neutrality then.Gel after handling is placed-20 ℃ of precooling 72h, and normal freeze-drying 24h promptly obtains gentamycin sulfate sustained-release micro-spheres-gelatin-siloxanes three-dimensional porous rack material after the lyophilizing afterwards.
Embodiment 3
With the dissolve with hydrochloric acid solution gentamycin sulfate sustained-release micro-spheres 0.1g of 20mL 0.1M, in above-mentioned solution, add 2g gelatin, 50 ℃ of following stirring and dissolving.Add lime nitrate and GPSM more successively, wherein lime nitrate/gelatin is (mass ratio) 0.1/1; The GPSM/ gelatin is (mass ratio) 1/1.Above-mentioned solution fully mixes 2h, to fully even (not having phase-splitting), pours into then in the mould of 5cmX 8cm, seals, and carries out sol gel reaction in 40 ℃ of calorstats, takes out after 1 day, obtains gentamycin sulfate sustained-release micro-spheres-gelatin-silicone gel.The ammonia spirit 20mL that adds 1.5M in above-mentioned mould places 16h down at 40 ℃, uses distilled water flushing until neutrality then.Gel after handling is placed-20 ℃ of precooling 72h, and normal freeze-drying 24h promptly obtains gentamycin sulfate sustained-release micro-spheres-gelatin-siloxanes three-dimensional porous rack material after the lyophilizing afterwards.
Embodiment 4
With the dissolve with hydrochloric acid solution gentamycin sulfate sustained-release micro-spheres 0.05g of 20mL 0.1M, in above-mentioned solution, add 2g gelatin, 55 ℃ of following stirring and dissolving.Add lime nitrate and GPSM more successively, wherein lime nitrate/gelatin is (mass ratio) 0.1/1; The GPSM/ gelatin is (mass ratio) 1.5/1.Above-mentioned solution fully mixes 2h, to fully even (not having phase-splitting), pours into then in the mould of 5cm * 8cm, seals, and carries out sol gel reaction in 40 ℃ of calorstats, takes out after 1 day, obtains gentamycin sulfate sustained-release micro-spheres-gelatin-silicone gel.The ammonia spirit 20mL that adds 2M in above-mentioned mould places 16h down at 40 ℃, uses distilled water flushing until neutrality then.Gel after handling is placed-20 ℃ of precooling 72h, and normal freeze-drying 24h promptly obtains gentamycin sulfate sustained-release micro-spheres-gelatin-siloxanes three-dimensional porous rack material after the lyophilizing afterwards.
Embodiment 5～8
Anti-microbial property is estimated
The preparation method of gentamycin sulfate sustained-release micro-spheres-gelatin-siloxanes three-dimensional porous rack material is with embodiment 1, the anti-microbial property of prepared material tested with sterilization rate by the inhibition zone experiment estimate.After the timbering material sterilization, use card punch to be made as diameter and be 7mm, the cylindrical sample of high 2mm.The blank timbering material of no gentamycin and microsphere is as negative control.Picking escherichia coli (E.coli, DH5 α) bacterium colony adds 5mL LB fluid medium, and under 37 ℃ of conditions, incubated overnight in the 250rpm shaken cultivation case, density are 1 * 10
6Cfu/mL bacterium liquid is used for the anti-microbial property evaluation test of material.
(1) inhibition zone experiment
The inhibition zone experiment, promptly (agar diffusion test ADT), can be used to evaluating material anti-microbial property qualitatively to agar diffusion spare side.At first, 40 μ L bacterium liquid evenly are tiled in LB solid culture primary surface, the material sample branch intersperses among on the culture medium.Then, culture dish is placed in the constant incubator, under 37 ℃ of conditions, cultivate 24h.After cultivating end, with the diameter (Dh/mm) of scope of restraining fungi around the vernier caliper measurement material sample.Be to guarantee the accuracy of data, every 120 ° along different directions, to the scope of restraining fungi diameter measurement of each material sample 3 times, every kind of anti-biotic material got 3 samples and carried out the inhibition zone experiment, data are got the meansigma methods of each sample scope of restraining fungi.Material inhibition zone size should deduct (Ds/mm) size of material diameter.Inhibition zone size (mm)=(Dh-Ds) * 1/2 the results are shown in Table 1.
(2) sterilization rate test
The material that obtains is carried out the sterilization rate test.According to the sterilization rate test, 80 μ L bacteria concentrations are 1 * 10
6The bacillus coli DH 5 alpha of cfu/mL contacts cultivation with timbering material, cultivate 24h under 37 ℃ of conditions.Bacterium liquid under the flushing on the material dilutes counting.The computational methods of sterilization filter are: sterilization rate=(the bacterium number after the bacterium number-cultivation before cultivating)/(the bacterium number before cultivating) x100%.After cultivating 24h altogether with antibacterial, gentamycin sulfate sustained-release micro-spheres-gelatin-siloxanes three-dimensional porous rack material is fairly obvious for the growth inhibited of antibacterial, and the clump count alive of antibacterial has all reduced about 90%.And after antibacterial and the compound timbering material of no medicine carrying microsphere cultivated 24h altogether, the clump count alive of antibacterial had increased about 75.75% (table 1).Fig. 6 is the inhibition zone photo around the timbering material, as seen from the figure, there is tangible inhibition zone (material I, II and III) to occur around the gentamycin sulfate sustained-release micro-spheres-gelatin-siloxanes three-dimensional porous rack material of different proportionings, do not have the compound timbering material IV of medicine carrying microsphere and inhibition zone then do not occur, the gelatin-siloxanes porous support materials that therefore is compounded with medicine carrying microballoons has good antibacterial performance.
The anti-microbial property of table 1 timbering material
In the table
1f
GFor GPSM with (mass ratio of gelatin+GPSM),
2f
GSFor gentamycin sulfate with (mass ratio of gentamycin sulfate+gelatin+GPSM),
3f
MBe the mass ratio of medicine carrying microballoons with (gelatin+medicine carrying microballoons),
4f
CaBe lime nitrate and the (mass ratio of gelatin+lime nitrate+GPSM).
Claims (10)
1. composite organization engineering stent material by using with anti-infection property, it is characterized in that being antibiotic microspheres-gelatin-siloxanes three-dimensional porous tissue engineering bracket material, by antibiotic microspheres, gelatin, 3-(2,3-epoxy third oxygen) propyl trimethoxy silicane and calcium salt are composited, each set of dispense is a gelatin 1 than by mass fraction, antibiotic microspheres 0.01～0.1, and 3-(2,3-epoxy third oxygen) propyl trimethoxy silicane 0.5～1.5, calcium salt 0.01～0.2.
2. a kind of preparation method with composite organization engineering stent material by using of anti-infection property as claimed in claim 1 is characterized in that may further comprise the steps:
1) freeze dried antibiotic microspheres is dispersed in the acid solution, adds gelatin then, obtain solution A after the dissolving;
2) in solution A, add calcium salt and obtain solution B;
3) in solution B, add 3-(2,3-epoxy third oxygen) propyl trimethoxy silicane, mix solution C;
4) solution C is injected mould,, get antibiotic microspheres-gelatin-silicone gel through sol-gel process;
5) inject ammonia spirit in the mould that antibiotic microspheres-gelatin-silicone gel is housed, soak gel, the demoulding is cleaned;
6) adopt freezing-lyophilization that antibiotic microspheres-gelatin-silicone gel is handled, obtain having the antibiotic microspheres-gelatin-siloxanes three-dimensional porous tissue engineering bracket material of different pore-size distributions after the lyophilizing.
3. a kind of preparation method as claimed in claim 2 with composite organization engineering stent material by using of anti-infection property, it is characterized in that in step 1), press mass ratio, antibiotic microspheres: gelatin is 0.01～0.1: 1, and described acid is at least a in acetic acid, formic acid, the hydrochloric acid.
4. a kind of preparation method with composite organization engineering stent material by using of anti-infection property as claimed in claim 2 is characterized in that in step 2) in, press mass ratio, calcium salt: gelatin is 0.01～0.2: 1.
5. as claim 2 or 4 described a kind of preparation methoies, it is characterized in that in step 2 with composite organization engineering stent material by using of anti-infection property) in, described calcium salt is a soluble calcium salt, described soluble calcium salt is selected from lime nitrate, calcium sulfate or calcium chloride.
6. a kind of preparation method as claimed in claim 2 with composite organization engineering stent material by using of anti-infection property, it is characterized in that pressing mass ratio in step 3), 3-(2,3-epoxy third oxygen) propyl trimethoxy silicane: gelatin is 0.5～1.5: 1, and described blended temperature is 40～60 ℃.
7. a kind of preparation method with composite organization engineering stent material by using of anti-infection property as claimed in claim 2 is characterized in that in step 4) the temperature of described sol-gel process is 40～60 ℃.
8. a kind of preparation method as claimed in claim 2 with composite organization engineering stent material by using of anti-infection property, it is characterized in that in step 5), the concentration of described ammonia spirit is 0.5～3M, the temperature of described immersion gel is 20～40 ℃, the time of soaking gel is 8～24h, described cleaning washed with de-ionized water.
9. a kind of preparation method as claimed in claim 2 with composite organization engineering stent material by using of anti-infection property, it is characterized in that in step 6), described employing is freezing-lyophilization to antibiotic microspheres-gelatin-silicone gel handle is earlier-20～-80 ℃ freezing down, described freeze dried temperature is-80～-200 ℃.
10. a kind of preparation method with composite organization engineering stent material by using of anti-infection property as claimed in claim 2 is characterized in that the preparation method of described antibiotic-gelatin-silicone microsphere is as follows:
1) the preparation gelatine content is 0.5%～1.5% acid solution; Described acid is at least a in formic acid, acetic acid, the hydrochloric acid;
2) in the acid solution of gelatin, add 3-(2,3-epoxy third oxygen) propyl trimethoxy silicane, under 40～60 ℃ of temperature, stirred 3～5 days; The mass ratio of 3-(2,3-epoxy third oxygen) propyl trimethoxy silicane and gelatin is 0.5～1.5: 1;
3) by quality than antibiotic: gelatin is to add antibiotic, stirring and dissolving at 0.1～2: 1;
4) by quality than tween 80: gelatin is to add tween 80 at 0.5～5: 1, stirs 10～20min, drips the metabisulfite solution of 20wt%, occurs opalescence until solution colour by colourless becoming, and stops to drip;
5) continue to stir 20～24h, obtain antibiotic-gelatin-silicone microsphere solution, clean the conventional lyophilizing in back and preserve.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2009101127579A CN101698115B (en) | 2009-11-03 | 2009-11-03 | Composite tissue engineering scaffold material with anti-infection property and manufacturing method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2009101127579A CN101698115B (en) | 2009-11-03 | 2009-11-03 | Composite tissue engineering scaffold material with anti-infection property and manufacturing method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101698115A true CN101698115A (en) | 2010-04-28 |
| CN101698115B CN101698115B (en) | 2012-11-28 |
Family
ID=42146581
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2009101127579A Expired - Fee Related CN101698115B (en) | 2009-11-03 | 2009-11-03 | Composite tissue engineering scaffold material with anti-infection property and manufacturing method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101698115B (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103239758A (en) * | 2012-02-14 | 2013-08-14 | 深圳兰度生物材料有限公司 | Artificial dermis bracket and preparation method of artificial dermis bracket |
| CN104448828A (en) * | 2013-09-12 | 2015-03-25 | 南方医科大学南方医院 | Antibacterial drug carrying microsphere silicone rubber composite |
| US9180094B2 (en) | 2011-10-12 | 2015-11-10 | The Texas A&M University System | High porosity materials, scaffolds, and method of making |
| US10363215B2 (en) | 2013-11-08 | 2019-07-30 | The Texas A&M University System | Porous microparticles with high loading efficiencies |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1278745C (en) * | 2004-11-21 | 2006-10-11 | 厦门大学 | Three-dimensional porous tissue engineering stand material and preparation thereof |
-
2009
- 2009-11-03 CN CN2009101127579A patent/CN101698115B/en not_active Expired - Fee Related
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9180094B2 (en) | 2011-10-12 | 2015-11-10 | The Texas A&M University System | High porosity materials, scaffolds, and method of making |
| CN103239758A (en) * | 2012-02-14 | 2013-08-14 | 深圳兰度生物材料有限公司 | Artificial dermis bracket and preparation method of artificial dermis bracket |
| CN103239758B (en) * | 2012-02-14 | 2015-01-21 | 深圳兰度生物材料有限公司 | Artificial dermis bracket and preparation method of artificial dermis bracket |
| CN104448828A (en) * | 2013-09-12 | 2015-03-25 | 南方医科大学南方医院 | Antibacterial drug carrying microsphere silicone rubber composite |
| CN104448828B (en) * | 2013-09-12 | 2017-03-01 | 南方医科大学南方医院 | The medicine carrying microballoonss silicon rubber composite material of antibacterial |
| US10363215B2 (en) | 2013-11-08 | 2019-07-30 | The Texas A&M University System | Porous microparticles with high loading efficiencies |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101698115B (en) | 2012-11-28 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Li et al. | One-pot, self-catalyzed synthesis of self-adherent hydrogels for photo-thermal, antimicrobial wound treatment | |
| Feng et al. | The effect of pore size on tissue ingrowth and neovascularization in porous bioceramics of controlled architecture in vivo | |
| Zhang et al. | Sr/ZnO doped titania nanotube array: an effective surface system with excellent osteoinductivity and self-antibacterial activity | |
| CN109200334B (en) | Composite hydrogel dressing for photodynamic therapy of wound infection and preparation method thereof | |
| CN105903057B (en) | Preparation method of nano silver hydridization silk gum porous gel anti-biotic material and products thereof and application | |
| CN103028145B (en) | Silk fibroin base integrated osteochondral two-layer bracket, preparation and application thereof | |
| CN101623518B (en) | Anti-infection bio-derived hernia and body wall repair material, preparation and application thereof | |
| CN104271166B (en) | Biomaterial based on absorbent cellulosic and implant | |
| CN101698115B (en) | Composite tissue engineering scaffold material with anti-infection property and manufacturing method thereof | |
| CN107213529B (en) | Preparation method of degradable medical high-molecular three-dimensional material for improving adhesion and osteogenic performance of osteoblasts | |
| CA2602905A1 (en) | Photocrosslinkable oligo(poly (ethylene glycol) fumarate) hydrogels for cell and drug delivery | |
| CN107320786B (en) | Slow-release anti-infection composite soft tissue repair material and preparation method thereof | |
| CN106267367A (en) | A kind of preparation method of the tooth implant that can be used for diabetics | |
| CN110721346A (en) | Biological 3D printing ink and preparation method thereof | |
| CN112618791A (en) | Polyether-ether-ketone three-dimensional porous and modified polydopamine/gentamicin for implant antibiosis, anti-inflammation and promotion of osseointegration | |
| US20010014355A1 (en) | Conditioning of bioactive glass surfaces in protein containing solutions | |
| CN103157129B (en) | polyamino acid/hydroxyapatite composite hydrogel for bone repair and preparation method thereof | |
| CN112773932B (en) | Vascularization promoting tissue repair material with oriented pore structure and preparation method and application thereof | |
| CN108744047B (en) | Preparation method of titanium nano/silk fibroin/hydroxyapatite composite medical titanium coating | |
| CN112076350B (en) | Biomimetic mineralized hydrogel with nano-micron composite structure and high mineral density as well as preparation method and application thereof | |
| CN104826163B (en) | A kind of compound support frame material for effectively improving bone injury reparation | |
| KR101243956B1 (en) | The coated scaffold for regeneration of hard tissue with components of bone matrix containing mesoporous bioactive glass by co-precipitation and the method thereof | |
| CN1278745C (en) | Three-dimensional porous tissue engineering stand material and preparation thereof | |
| CN108744032A (en) | A kind of polyelectrolyte film modified high molecular porous support materials and its preparation method and application | |
| CN110339403A (en) | Spherical nano hydroxyapatite/natural polymer biomimetic scaffolds and preparation method |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20121128 Termination date: 20151103 |
|
| EXPY | Termination of patent right or utility model |