4. INJECTABLE EXTRACELLULAR MATRIX DERIVED HYDROGEL ENHANCES RETENTION AND DELIVERY OF A HEPARIN BINDING GROWTH FACTOR IN ISCHEMIC MYOCARDIUM

Department: Bioengineering
Faculty Advisor(s): Karen Christman

Primary Student
Name: Sonya B Seif-Naraghi
Email: sseifnar@ucsd.edu
Phone: 858-534-9628
Grad Year: 2012

Abstract
Injectable hydrogels derived from the extracellular matrix (ECM) of decellularized tissues have recently emerged as scaffolds for tissue engineering applications. In this work, we investigated the utility of a decellularized pericardial matrix hydrogel for improved delivery of heparin-binding growth factors via native cues present in the material. Immobilization of growth factors on a scaffold has been previously shown to increase their stability and activity. This is often done via chemical crosslinking, covalent bonding, or by incorporating natural or synthetic growth factor binding domains similar to those found in vivo in sulfated glycosaminoglycans (GAGs). Many decellularized ECM-derived hydrogels retain native sulfated GAGs and, therefore, these materials may provide an excellent delivery platform for heparin-binding growth factors. In this study, the sulfated GAG content of an ECM hydrogel derived from decellularized pericardial ECM was confirmed with FTIR and its ability to bind basic fibroblast growth factor (bFGF) was established. By delivering the growth factor in the pericardial matrix hydrogel as compared to collagen, a commonly used biomaterial and a large component of the matrix hydrogel, retention of bFGF was increased both in vitro and in vivo. In a rodent infarct model, intramyocardial injection of bFGF in pericardial matrix enhanced neovascularization by approximately 112% compared to delivery in collagen. Importantly, the newly formed vasculature was anastomosed with existing vasculature. Thus, the sulfated GAG content of the decellularized ECM hydrogel provides a platform for incorporation of heparin binding growth factors for prolonged retention and delivery.

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