Growth factors engineered for super-affinity to the extracellular matrix enhance tissue healing

Mikaël M. Martino, Priscilla S. Briquez, Esra Guç̈, Federico Tortelli, Witold W. Kilarski, Stephanie Metzger, Jeffrey J. Rice, Gisela A. Kuhn, Ralph Mul̈ler, Melody A. Swartz, Jeffrey A. Hubbell

Research output: Contribution to journalArticleResearchpeer-review

298 Citations (Scopus)


Growth factors (GFs) are critical in tissue repair, but their translation to clinical use has been modest. Physiologically, GF interactions with extracellular matrix (ECM) components facilitate localized and spatially regulated signaling; therefore, we reasoned that the lack of ECM binding in their clinically used forms could underlie the limited translation. We discovered that a domain in placenta growth factor-2 (PlGF-2123-144) binds exceptionally strongly and promiscuously to ECM proteins. By fusing this domain to the GFs vascular endothelial growth factor-A, platelet-derived growth factor-BB, and bone morphogenetic protein-2, we generated engineered GF variants with super-affinity to the ECM. These ECM super-affinity GFs induced repair in rodent models of chronic wounds and bone defects that was greatly enhanced as compared to treatment with the wild-type GFs, demonstrating that this approach may be useful in several regenerative medicine applications.

Original languageEnglish
Pages (from-to)885-888
Number of pages4
Issue number6173
Publication statusPublished - 21 Feb 2014
Externally publishedYes

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