Pegylated insulin‐like growth factor‐1 biotherapeutic delivery promotes rotator cuff regeneration in a rat model
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 abili...
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Published in | Journal of biomedical materials research. Part A Vol. 110; no. 7; pp. 1356 - 1371 |
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Main Authors | , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Hoboken, USA
John Wiley & Sons, Inc
01.07.2022
Wiley Subscription Services, Inc |
Subjects | |
Online Access | Get full text |
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Summary: | 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. |
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Bibliography: | Funding information Anupama Prabhath and Varadraj N. Vernekar share co‐first authorship for this work. NIH Pioneer, Grant/Award Number: 1DP1OD019349‐01; Novartis, Grant/Award Number: G600795; National Institute of Arthritis and Musculoskeletal and Skin Diseases Ruth L. Kirschstein National Research Service Award (NRSA) Institutional Research Training Grant, Grant/Award Number: 1T32AR079114‐01 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1549-3296 1552-4965 |
DOI: | 10.1002/jbm.a.37378 |