浙江大学学报（医学版）2025，Vol.54Issue(4)：434-445,12.DOI:10.3724/zdxbyxb-2024-0698
基于微流控光固化技术制备丝素蛋白/透明质酸复合微球水凝胶
Microfluidic photo-curing fabrication of silk fibroin/hyaluronic acid composite microsphere hydrogels
摘要
Abstract
Objective:To fabricate an injectable composite microsphere hydrogel reinforced with silk fibroin/hyaluronic acid microspheres,achieving synergistic enhance-ment of mechanical robustness and biofunctionality.Methods:Methacrylated hyaluronic acid(HAMA)and thiolated silk fibroin(TSF)were synthesized.Monodisperse microspheres generated via microfluidics were UV-cured(420 nm)through thiol-ene click reaction.These microspheres were embedded in a TSF/HAMA matrix to form photo-cured composites.The grafting rate of TSF and HAMA was characterized by H1-NMR;particle size distribution of microsphere hydrogels in soybean oil was observed by optical microscopy;gel point of composite microsphere hydrogels was determined by advanced extensional rheometer;microscopic morphology of microsphere hydrogels was observed by scanning electron microscopy;elemental distribution of microsphere hydrogels was detected by X-ray energy dispersive spectroscopy;tunability of composite microsphere hydrogels was observed by inverted confocal microscopy;mechanical properties of composite microsphere hydrogels were tested by compression testing;swelling ratio,degradation rate and water retention rate of composite microsphere hydrogels were measured by gravimetric method.Cytotoxicity of the composite microsphere hydrogels was determined by Calcein-AM/propidium iodide dual staining and CCK-8 assay;cell migration capability was observed by scratch assay.Results:The grafting rates of HAMA and TSF was 48.03％and 17.99％,respectively.Microsphere hydrogels with particle sizes of(43.3±1.2),(78.1±3.0),and(130.8±1.9)μm were prepared.The gel time of the composite microsphere hydrogels was 48-115s.The laser confocal imaging confirmed dynamic regulation characteristics of the composite microsphere hydrogels.The compressive strength of the composite microsphere hydrogels reached 22.7 kPa and maintained structural integrity at 40％strain after 20 compression cycles.The composite microsphere hydrogels exhibited differential deswelling behaviors in simulated physiological environments,and reducing microsphere particle size could significantly enhance its stability under moist conditions.The degradation rate of the composite microsphere hydrogels was(49.1±0.9)％after 200 h,and water retention rate was maintained at 40％-60％after 96 h.Biocompatibility assays confirmed＞95％cell viability and unimpaired cell migration abilities.Conclusion:The TSF/HAMA composite microsphere hydrogel developed in this study has characteristics of rapid fabrication,adjustable mechanical properties,enhanced environmental stability and excellent biocom-patibility,thus providing a new material solution for tissue repair and regenerative medicine.关键词
微球水凝胶/硫基-烯点击化学反应/微流控/光固化/丝素蛋白/透明质酸/理化特征/生物相容性Key words
Microsphere hydrogel/Thiol-ene click reaction/Microfluidics/Photo-curing/Silk fibroin/Hyaluronic acid/Physicochemical property/Biocompatibility分类
医药卫生引用本文复制引用
王如月,陈韫陆,吴琛琦,李舒婧,刘震杰,陈枫..基于微流控光固化技术制备丝素蛋白/透明质酸复合微球水凝胶[J].浙江大学学报（医学版）,2025,54(4):434-445,12.基金项目
浙江省"尖兵""领雁"研发攻关计划(2024C03094) This study was supported by"Pioneer"and"Leading Goose"R&D Program of Zhejiang(2024C03094). （2024C03094）
