期刊
JOURNAL OF CONTROLLED RELEASE
卷 356, 期 -, 页码 162-174出版社
ELSEVIER
DOI: 10.1016/j.jconrel.2023.02.039
关键词
Tendon injury; IGFBP-4; IGF-1; Electrospun membrane; Dextran particle
Tendon injury is a common musculoskeletal disorder that limits joint mobility and reduces quality of life. Insulin-like growth factor binding protein 4 (IGFBP-4) has been identified as a potential therapeutic protein for tendon healing. In this study, an electrospun membrane was fabricated using IGFBP4-encapsulated dextran particles and poly (L-lactic acid) (PLLA) solution, which showed excellent cytocompatibility and sustained release of IGFBP-4. In rat Achilles tendon injury model, this scaffold promoted tendon healing at molecular, functional, ultrastructural, and biomechanical levels, potentially through IGF-1/AKT signaling pathway. This study suggests that the IGFBP4-PLLA electrospun membrane holds promise as a therapeutic strategy for tendon injury.
Tendon injury is one of the most common musculoskeletal disorders that impair joint mobility and lower quality of life. The limited regenerative capacity of tendon remains a clinical challenge. Local delivery of bioactive protein is a viable therapeutic approach for tendon healing. Insulin-like growth factor binding protein 4 (IGFBP-4) is a secreted protein capable of binding and stabilizing insulin-like growth factor 1 (IGF-1). Here, we applied an aqueous-aqueous freezing-induced phase separation technology to obtain the IGFBP4-encapsulated dextran particles. Then, we added the particles into poly (L-lactic acid) (PLLA) solution to fabricate IGFBP4-PLLA electrospun membrane for efficient IGFBP-4 delivery. The scaffold showed excellent cytocompatibility and a sustained release of IGFBP-4 for nearly 30 days. In cellular experiments, IGFBP-4 promoted tendon-related and proliferative markers expression. In a rat Achilles tendon injury model, immunohistochemistry and quantitative real-time polymerase chain reaction confirmed better outcomes by using the IGFBP4-PLLA electrospun mem-brane at the molecular level. Furthermore, the scaffold effectively promoted tendon healing in functional per-formance, ultrastructure and biomechanical properties. We found addition of IGFBP-4 promoted IGF-1 retention in tendon postoperatively and then facilitated protein synthesis via IGF-1/AKT signaling pathway. Overall, our IGFBP4-PLLA electrospun membrane provides a promising therapeutic strategy for tendon injury.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据