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通过区域免疫实现自限性炎症的电纺纤维带修复深部软组织。

Inflammation Self-Limiting Electrospun Fibrous Tape via Regional Immunity for Deep Soft Tissue Repair.

机构信息

Department of Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai, 200025, P. R. China.

出版信息

Small. 2022 Sep;18(39):e2203265. doi: 10.1002/smll.202203265. Epub 2022 Aug 28.

Abstract

Overexpression of inflammatory cytokines and chemokines occurs at deep soft tissue injury sites impeding the inflammation self-limiting and impairing the tissue remodeling process. Inspired by the electrostatically extracellular matrix (ECM) binding property of the inflammatory signals, an inflammation self-limiting fibrous tape is designed by covalently modifying the thermosensitive methacrylated gelatin (GelMA) and negatively charged methacrylated heparin (HepMA) hydrogel mixture with proper ratio onto the electrospun fibrous membrane by mild alkali hydrolysis and carboxyl-amino condensation reaction to restore inflammation self-limiting and promote tissue repair via regional immunity regulation. While the GelMA guarantees cell compatibility, the negatively charged HepMA successfully adsorbs the inflammatory cytokines and chemokines by electrostatic interactions and inhibits immune cell migration in vitro. Furthermore, in vivo inflammation self-limiting and regional immunity regulation efficacy is evaluated in a rat abdominal hernia model. Reduced local inflammatory cytokines and chemokines in the early stage and increased angiogenesis and ECM remodeling in the later phase confirm that the tape is an approach to maintain an optimal regional immune activation level after soft tissue injury. Overall, the reported electrospun fibrous tape will find its way into clinical transformation and solve the challenges of deep soft tissue injury.

摘要

在深部软组织损伤部位,炎症细胞因子和趋化因子的过度表达会阻碍炎症的自我限制,并损害组织重塑过程。受炎症信号静电结合细胞外基质(ECM)特性的启发,通过温和碱水解和羧基-氨基缩合反应,将具有适当比例的热响应性甲基丙烯酰化明胶(GelMA)和带负电荷的甲基丙烯酰化肝素(HepMA)水凝胶混合物共价修饰到电纺纤维膜上,设计了一种具有炎症自我限制功能的纤维带,从而恢复炎症的自我限制并通过局部免疫调节促进组织修复。GelMA 保证了细胞相容性,带负电荷的 HepMA 通过静电相互作用成功吸附炎症细胞因子和趋化因子,并抑制体外免疫细胞迁移。此外,在大鼠腹疝模型中评估了体内炎症自我限制和局部免疫调节的功效。早期局部炎症细胞因子和趋化因子减少,后期血管生成和 ECM 重塑增加,证实该胶带是一种在软组织损伤后维持局部免疫激活水平的方法。总的来说,所报道的电纺纤维带将有望转化为临床应用,并解决深部软组织损伤的挑战。

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