Abstract P1141: Heparinized Alginate And Collagen-based Hydrogels Enhance Localized Vascularization In Ischemic Tissue

Abstract

Over 800,000 myocardial infarctions (MI) occur annually in the United States alone, 25% of which represent a repeat occurrence further indicating chronic ischemia in the myocardium. Cardiovascular regeneration is largely dependent on the stimulation of blood vessel development for recovering tissue perfusion and modulating ventricular remodeling. The delivery of angiogenic growth factors and cytokines has demonstrated the ability to initiate angiogenesis and vascular network formation in cardiac tissue, with localization of bioactive molecules more effective than systemic delivery. Alginate, with its high biocompatibility and biodegradation, represents a promising hydrogel material for factor delivery due to its high protein loading capacity. We hypothesize that covalently binding heparin to alginate will increase binding and retention to subsequently lengthen the local release duration of vascular-promoting factors. For greater tuning and biointegration, collagen and alginate hydrogel designs were optimized for both injection and co-implantation of a solid film with hiPSC-CM based ECTs in a rat model of myocardial infarction. Injectable and solid formulations showed stiffnesses of 50 +/- 2 kPa and 900 +/- 193 kPa, respectively, which was maintained for up to 6 hours of dry time. Release profiles showed sustained growth factor release, with 65% of the total content released at 7 days and 100% release in 14 days. In vitro evaluation using human induced pluripotent stem cell-derived endothelial cells (hiPSC-ECs) showed cell viability and primitive network formation. In vivo subcutaneous injections showed host-vessel penetration into the delivered biomaterial within 4 days. Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) loaded injections demonstrated an average lumen density of 80 +/- 15 vessels/mm 2 when compared to 4 +/- 1 vessels/mm 2 in the unloaded controls. In conclusion, we have designed a biomaterial system for disparate delivery models and shown successful vascularization of the biomaterial, demonstrating the versatile vascular regenerative capabilities of the hydrogel design.