转化生长因子明胶微球制备及体外缓释研究Fabrication of TGFβ_1-gelatin microspheres and in vitro releasing study
范宏斌,胡蕴玉,吴红,李旭升,王军,白建萍,吕荣
摘要(Abstract):
目的: 研制转化生长因子β1 (TGFβ1 ) 缓释明胶微球, 探索将微球药物控释系统引入组织工程学领域的可行性。方法: 采用改良的双相乳化冷凝聚合法制备明胶微球, 将其与TGFβ1 复合, 观察微球分散度、粒径及外观形态; 计算微球包封率、载药率及体外释药特性;分别使用缓释微球、诱导液 (含TGFβ1 4. 5ng/ml) 诱导兔骨髓间充质干细胞 (MSCs) 6d, 免疫组化检测Ⅱ型胶原、S 100蛋白表达。结果: 微球大小均匀, 平均直径 ( 15. 1±3. 4 )μ, 载药量为 900ng/g, 包封率为90. 0%, 体外 7d内药物缓释 92%; 缓释微球可持续释放具有生物活性的TGFβ1 诱导MSCs, 6d后细胞Ⅱ型胶原、S 100蛋白免疫组化染色阳性, 而诱导液组Ⅱ型胶原、S 100蛋白免疫组化染色阴性。结论: TGFβ1 明胶微球具有良好的药物缓释功能, 体外可持续诱导MSCs向软骨细胞分化, 维持细胞表型。为软骨组织工程中生长因子能够持续高效发挥作用提供一种新途径。
关键词(KeyWords): 微球;骨髓基质干细胞;组织工程;软骨
基金项目(Foundation): 国家“九五”高技术计划新材料领域基金资助项目 (编号: 009 0160)
作者(Author): 范宏斌,胡蕴玉,吴红,李旭升,王军,白建萍,吕荣
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参考文献(References):
- [1]Reddia.Morphogenesisandtissueengineeringofboneandcartilage:inductivesignals, stemcellsandbiomimeticbiomaterials[J].TissueEng,2000,6(4):351~359.
- [2]SungEunKim,JaeHyungPark,YongWooCho,etal.Porouschi tosanscaffoldcontainingmicrospheresloadedwithtransforminggrowthfactor bl:Implicationsforcartilagetissueengineering[J].JControlledRelease,2003,91:365~374.
- [3]TheresaA.Holland,YasuhikoTabata,AntoniosG.Mikos, etal.Invitroreleaseoftransforminggrowthfactorβ1 fromgelatinmicroparti clesencapsulatedinbiodegradable, injectableoligo(poly(ethyleneglycol)fumarate)hydrogels[J].JControlledRelease,2003,91:299~313.
- [4]Llullr.Immuneconsiderationsintissueengineering[J].ClinPlastSurg,1999,26(4):549~568.
- [5]RuoslahtiE,PierschbacherMD.ArgGlyAsp: aversatilecellrecog nitionsignal[J].Cell,1986,44:517.
- [6]TheresaA.Holland,AntoniosG.Mikos.Advancesindrugdeliveryforarticularcartilage[J].JControlledRelease,2003,91:365~374.
- [7]GangHuanga,JunGaoa,ZhibingHua,etal.Controlleddrugreleasefromhydrogelnanoparticlenetworks[J].JControlledRelease,2004,94:303~311.