Abstract：
Cluster-like collective cell migration of fibroblasts is one of the main factors of adhesion in injured tissues. In this research, a microdot biomaterial system is constructed using α-helical polypeptide nanoparticles and anti-inflammatory micelles, which are prepared by ring-opening polymerization of α-amino acids-N-carboxylic anhydrides (NCAs) and lactide, respectively. The microdot biomaterial system slowly releases functionalized polypeptides targeting mitochondria and promoting the influx of extracellular calcium ions under the inflammatory environment, thus inhibiting the expression of N-cadherin mediating cell-cell interaction, and promoting apoptosis of cluster fibroblasts, synergistically inhibiting the migration of fibroblast clusters at the site of tendon injury. Meanwhile, the anti-inflammatory micelles are celecoxib (Cex) solubilized by PEG/polyester, which can improve the inflammatory microenvironment at the injury site for a long time. In vitro, the microdot biomaterial system can effectively inhibit the migration of the cluster fibroblasts by inhibiting the expression of N-cadherin between cell-cell and promoting apoptosis. In vivo, the microdot biomaterial system can promote apoptosis while achieving long-acting anti-inflammation effects, and reduce the expression of vimentin and α-smooth muscle actin (α-SMA) in fibroblasts. Thus, this microdot biomaterial system provides new ideas for the prevention and treatment of tendon adhesion by inhibiting the cluster migration of fibroblasts.
摘要：
成纤维细胞的簇状集体细胞迁移是损伤组织粘附的主要因素之一。在这项研究中,使用α-螺旋多肽纳米颗粒和抗炎胶束构建了一个微点生物材料系统，通过α-氨基酸-N-羧酸酐（NCAs）和丙交酯的开环聚合制备，分别。微点生物材料系统在炎症环境下缓慢释放靶向线粒体的功能化多肽，促进细胞外钙离子的流入，从而抑制N-cadherin介导细胞间相互作用的表达，促进簇成纤维细胞的凋亡，协同抑制成纤维细胞团簇在肌腱损伤部位的迁移。同时,微点生物材料系统中的抗炎胶束是通过PEG/聚酯溶解的塞来昔布（Cex），可以长期改善损伤部位的炎症微环境。体外，微点生物材料系统可以通过抑制细胞间N-cadherin的表达和促进细胞凋亡来有效抑制簇状成纤维细胞的迁移。在体内,microdot生物材料系统可以促进细胞凋亡，同时实现长效抗炎作用，并降低成纤维细胞中波形蛋白和α-平滑肌肌动蛋白的表达。因此，该microdot生物材料系统通过抑制成纤维细胞的簇迁移为预防和治疗肌腱粘连提供了新的思路。本文受版权保护。保留所有权利。
