Covalently Immobilized Platelet Derived Growth Factor-BB Promotes Angiogenesis in Biomimetic Poly(ethylene glycol) Hydrogels

Periodical: Acta Biomater ISBN: 1878-7568 (Electronic) 1742-7061 (Linking)  Date: 2010/08/31  Language: Eng

Authors:Saik, J. E., Gould, D. J., Watkins, E. M., Dickinson, M. E., West, J. L.

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Abstract
The field of tissue engineering is severely limited by the lack of microvascularization in tissue engineered constructs. Biomimetic poly(ethylene glycol) hydrogels containing covalently immobilized platelet-derived growth factor BB (PDGF-BB) were developed to promote angiogenesis. Poly(ethylene glycol) hydrogels resist protein absorption and subsequent nonspecific cell adhesion, thus providing a "blank slate," which can be modified through the incorporation of cell adhesive ligands and growth factors. PDGF-BB is a key angiogenic protein able to support neovessel stabilization by inducing functional anastomoses and recruiting pericytes. Due to PDGF`s widespread effects in the body and half life of only thirty minutes in circulating blood, immobilization of PDGF-BB may be necessary. In this work, bioactive, covalently immobilized PDGF-BB was shown to induce tubulogenesis on 2D modified surfaces, migration in 3D degradable hydrogels, and angiogenesis in a mouse cornea micropocket angiogenesis assay. Covalently immobilized PDGF-BB was also used in combination with covalently immobilized FGF-2, which led to significantly increased endothelial cell migration in 3D degradable hydrogels as compared to presentation of each factor alone. When a co-culture of endothelial cell and mouse pericyte precursor 10T1/2 cells was seeded onto modified surfaces, tubule formation was independent of surface modifications with covalently immobilized growth factors. Furthermore, the combination of soluble PDGF-BB and immobilized PDGF-BB induced a more robust vascular response as compared to soluble PDGF-BB alone when implanted into an in vivo mouse cornea micropocket angiogenesis assay. Based on these results, we believe bioactive hydrogels can be tailored to improve the formation of functional microvasculature for tissue engineering.