摘要
以生物相容性好且可降解的端基双键化的聚(ε-己内酯)(PCL)或聚(4-甲基-ε-己内酯)(PMCL)为基体,通过乳化剂Hypermer T96制备高内相乳液(HIPE)。该乳液在紫外光引发下,通过后加入的季戊四醇四-3-巯基丙酸酯(PETMP)与碳碳双键化的PCL(PCL-AC)或者PMCL(PMCL-AC)发生巯基-烯点击反应而交联成聚高内相乳液(PolyHIPE),经冷冻干燥得到PolyHIPE三维多孔支架。采用扫描电子显微镜、差示扫描量热仪、万能材料试验仪对支架的微观形貌、热力学以及力学性能进行了表征。通过体外细胞毒性实验以及肝细胞培养实验对支架的生物学性能进行了评估。力学性能测试结果表明:在乳液制备过程中,去离子水温度对支架的力学性能影响更为显著。体外细胞毒性以及肝细胞培养结果表明:支架无细胞毒性,且支架的刚性越小越有利于肝细胞的增殖和功能表达。
High interconnected porous characteristics of poly(high internal phase emulsion)(PolyHIPE)and good biocompatibility of poly(ε-caprolactone)(PCL)were combined to create 3Dporous polyesterbased PolyHIPE scaffolds.First,ring opening polymerization(ROP)ofε-caprolactone(CL)or 4-methyl-ε-caprolactone(MeCL)was carried out using 1,4-benzenedimethanol as initiator and Sn(Oct)2as catalyst,followed by acrylation of both hydroxyl ends.Then,Hypermer T96 was used to emulsify the dichloromethane/water mixing system to obtain high internal phase emulsion(HIPE,internal volume fraction was above 74%),where pentaerythritol tetra(3-mercaptopropionate)(PETMP)was added afterwards.Finally,under UV light irradiating,thiol-ene click cross-linking took place in continuous phase to form high interconnected porous polyester-based PolyHIPE scaffolds.The structure of PCL or poly(4-methyl-ε-caprolactone)(PMCL)and acrylation of the polymers were characterized by nuclear magnetic resonance(1 H-NMR)and gel permeation chromatography(GPC).Cross-linking conditions for PolyHIPE were also studied by scanning electron microscopy(SEM),differential scanning calorimeter(DSC)and universal material tester to reveal the microstructure,thermodynamics and mechanical properties of the porous PolyHIPE scaffolds,respectively.Moreover,biological properties of the scaffolds were evaluated by cytotoxicity assessment and hepatocyte culture experiment in vitro.Results showed that polymerization and complete acrylation of PCL and PMCL were successfully achieved.In addition,the stability of the emulsion could be adjusted by controlling molecular weight of PCL or PMCL,water content and temperature of internal phase.Furthermore,the water temperature of HIPE had a more dominant influence on thermodynamics and mechanical properties of PolyHIPEs than the water content did.Higher water temperature of HIPE led to higher glass-transition temperature(Tg)of the scaffold,as well as lower stiffness.Soxhlet-extracted PolyHIPE scaffolds were almost non-toxic in vitro.For hepatocyte culture,the lower stiffness of scaffolds was beneficial for cell proliferation and function express.
引文
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