Prabhath, Anupama , Vernekar , Varadraj N, Esdaille, Caldon J, Eisenberg , Ellen , Lebaschi , Amir, Badon , Mary , Seyedsalehi, Amir, Dzidotor , Godwin , Tang, Xiaoyan , Dyment , Nathaniel , Thomopoulos , Stavros , Kumbar , Sangamesh G, Deymier, Alix, Weber, Eckhard and Laurencin , Cato T (2022) Pegylated insulin-like growth factor-1 biotherapeutic delivery promotes rotator cuff regeneration in a rat model. Journal of biomedical materials research. Part A. ISSN 1552-4965

Abstract

Tears in the rotator cuff are challenging to repair because of the complex, hypocellular, hypovascular, and movement-active nature of the tendon and its enthesis. Insulin-like Growth Factor-1 (IGF-1) is a promising therapeutic for this repair. However, its unstable nature, short half-life, and ability to disrupt homeostasis has limited its clinical translation. Pegylation has been shown to improve the stability and sustain IGF-1 levels in the systemic circulation without disrupting homeostasis. To provide localized delivery of IGF-1 in the repaired tendons, we encapsulated pegylated IGF-1 mimic and its controls (unpegylated IGF-1 mimic and recombinant human IGF-1) in polycaprolactone-based matrices and evaluated them in a pre-clinical rodent model of rotator cuff repair. Pegylated-IGF-1 mimic delivery reestablished the characteristic tendon-to-bone enthesis structure and improved tendon tensile properties within 8 weeks of repair compared to controls, signifying the importance of pegylation in this complex tissue regeneration. These results demonstrate a simple and scalable biologic delivery technology alternative to tissue-derived grafts for soft tissue repair.

Item Type:	Article
Date Deposited:	08 Apr 2022 00:45
Last Modified:	08 Apr 2022 00:45
URI:	https://oak.novartis.com/id/eprint/42950