Abstract This study designed a novel porous PDLLA microspheres/collagen gel composite combined with fibroblasts as the injectable dermal filler for soft-tissue augmentation. The low degradation rate of porous PDLLA microspheres and seed cells were introduced in the system to achieve the filling volume stability and stronger regeneration activity. Biodegradable PDLLA porous microspheres were prepared by an improved water-in-oil-in-water double emulsion solvent evaporation method. The combine of fibroblasts with porous microspheres was observed through co-culture of cells with microspheres, SEM (scanning electron microscope) and fluorescent staining technology. The MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, the hemolysis test and histocompatibility experiment indicated that the composite had satisfactory biocompatibility in vitro and in vivo. In the animal studies, the composite was implanted into the subcutaneous part of the rats’ back through sterile needles. The collagen was metabolized within 30 days, meanwhile, fibroblasts-porous PDLLA microspheres served as scaffold structure and seed cells which promote new connective tissue formation. The histopathological studies demonstrate that the fibroblasts-porous PDLLA microspheres/collagen gel composite group could create larger amount of supportive structure than PDLLA porous microspheres/collagen gel composite group. All the results indicate that fibroblasts-porous PDLLA microspheres/collagen gel composite may have great clinical application in soft-tissue augmentation with its excellent biocompatibility, regeneration activity and stable long-term filling ability.

中文翻译：

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一种用于软组织填充的新型可注射成纤维细胞-多孔 PDLLA 微球/胶原凝胶复合材料

摘要 本研究设计了一种新型多孔 PDLLA 微球/胶原凝胶复合材料，结合成纤维细胞作为用于软组织填充的可注射真皮填充剂。系统中引入了多孔PDLLA微球和种子细胞的低降解率，以实现填充体积的稳定性和更强的再生活性。采用改进的水包油包水双乳液溶剂蒸发法制备了可生物降解的 PDLLA 多孔微球。通过细胞与微球共培养、SEM（扫描电子显微镜）和荧光染色技术观察成纤维细胞与多孔微球的结合。MTT (3-(4,5-二甲基噻唑-2-基)-2,5-二苯基溴化四唑)测定，溶血试验和组织相容性试验表明，该复合物具有良好的体外和体内生物相容性。在动物研究中，复合材料通过无菌针头植入大鼠背部的皮下部分。胶原蛋白在 30 天内被代谢，同时，成纤维细胞多孔 PDLLA 微球作为支架结构和种子细胞，促进新结缔组织的形成。组织病理学研究表明，与PDLLA多孔微球/胶原凝胶复合组相比，成纤维细胞-多孔PDLLA微球/胶原凝胶复合组可以产生更多的支持结构。