Molecularly regulated release of growth factors from programmable hydrogels for angiogenesis

Abstract

Event Abstract Back to Event Molecularly regulated release of growth factors from programmable hydrogels for angiogenesis Yong Wang1*, Nan Zhao1, Xiaolong Zhang1*, Li-Juan Duan2* and Guo-Hua Fong2* 1 Penn State University, Department of Biomedical Engineering, United States 2 UConn Health Center, Center for Vascular Biology, United States Introduction: Vascularization is important to treatment of ischemic diseases and survival of tissue-engineered constructs[1]. Delivery of growth factors is a promising strategy for vascularization. However, polymeric systems for growth factor delivery face several challenges including denaturation of growth factors, difficulty of controlling growth factor release kinetics, and/or lack of macroporous structures for cell growth[2]. The purpose of this work was to demonstrate that oligonucleotide aptamers and macroporous hydrogels could be used to develop a multifunctional biomaterial with great potential of overcoming all of these challenges. Materials and Methods: The multifunctional hydrogel was synthesized in a cylindrical mold with free radical polymerization and gas formation[3]. The key components in the pregel solution were oligonucleotide aptamers and acrylated gelatin that were incorporated into the hydrogel during the polymerization. The incorporation efficiency was determined by protein and oligonucleotide staining assays. The hydrogel was thoroughly washed to remove unreacted monomers and immersed in solution with VEGF and PDGF-BB for growth factor sequestration. The kinetics of growth factor release was examined using ELISA. The bioactivity of released or retained growth factors was measured using the standard HUVEC tube formation assay. To demonstrate directly the ability of this new hydrogel in promoting angiogenesis, the hydrogels with growth factors were subcutaneously implanted into a mouse model. The hydrogels were collected and analyzed after 4-week implantation. Endothelial cell surface biomarker CD31 was stained to examine populated vascular lumens in the hydrogels and tissues adjacent to the hydrogels. Results and Discussion: Macroporous hydrogels were successfully synthesized with free radical polymerization coupled with gas formation. The SEM images show that macroporous structures had an average pore diameter of 50 microns (Figure 1a). Both aptamers and gelatin were efficiently incorporated into the hydrogel network. Importantly, growth factors could be rapidly sequestered into the hydrogel network. When the superporous hydrogels were immersed into release media, aptamers effectively reduced the burst release effect and prolonged the growth factor release with desired kinetics. Moreover, the released and retained growth factors maintained high bioactivity (Figure 1b). For instance, at the end of two weeks, VEGF could maintain ~50% bioactivity that is much higher than the data reported in the literature. The animal studies showed that the multifunctional hydrogel stimulated angiogenesis much more effectively than the control hydrogels without aptamers (Figure 1c). Conclusions: Aptamer-functionalized hydrogels are a promising multifunctional biomaterial for controlled growth factor release. They hold great potential to stimulate vascularization for treatment of ischemic diseases or enhance survival of tissue-engineered constructs. U.S. NSF CAREER program under award number DMR-1332351; the National Heart, Lung, and Blood Institute of the NIH under award number R01HL122311