Insulin-like growth factor binding protein 4 loaded electrospun membrane ameliorating tendon injury by promoting retention of IGF-1.

Abstract

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 membrane at the molecular level. Furthermore, the scaffold effectively promoted tendon healing in functional performance, 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.

• Authors: Hui Wang, Ruyue Yu, Meng Wang, Shikun Wang, Xingyu Ouyang, Zhiwen Yan, Shuai Chen, Wei Wang, Fei Wu, Cunyi Fan
• Journal: Journal of controlled release : official journal of the Controlled Release Society (J Control Release) Vol. 356 Pg. 162-174 (04 2023) ISSN: 1873-4995 [Electronic] Netherlands
• PMID: 36868516 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.

Chemical References

• Insulin-Like Growth Factor Binding Protein 4
• Insulin-Like Growth Factor I
• RNA, Messenger

Topics

• Rats
• Animals
• Insulin-Like Growth Factor Binding Protein 4 (metabolism)
• Insulin-Like Growth Factor I
• Quality of Life
• RNA, Messenger (metabolism)
• Tendon Injuries (drug therapy)