Abstract 18277: Bioadhesive and Biodegradable Hyaluronic Acid-Serum Hydrogel Promotes Cardiac Regeneration

Abstract

Cellular cardiomyoplasty is limited by low levels of engraftment due to cell egress from injection site and death due to anoikis/necrosis. We hypothesized that tissue-engineered scaffolds that promote rapid cell adhesion would promote transplanted cell engraftment. We custom-designed stem cell niches, examined encapsulated stem cell viability, proliferation and 18 FDG uptake. Acute cardiac retention was measured by cut/count after transplantation of 18 FDG labeled rat cardiosphere derived cells (CDCs), in vivo transplanted cell bioenergetics by dual isotope SPECT/CT imaging of Na-Iodide symporter + CDCs (after 99m Tc-pertechnetate administration), and chronic engraftment by bioluminescence imaging (BLI) of luciferase + CDCs; LV function was assessed by echocardiography. Crosslinking of N-hydroxysuccinimide-derivatized hyaluronic acid with autologous serum yielded bioadhesive, biodegradable hydrogels (HA:Ser) that promoted survival and proliferation of mouse embryonic stem cells, human mesenchymal stem cells, and CDCs (viability: 99%, 93%, and 95%; proliferation: 759%, 126%, and 322%, respectively at d7; n=3, p< 0.05). I n vitro 18 FDG uptake revealed rapid depression (0.13±0.01%ID/μg DNA) following trypsinization and prompt restoration by encapsulation in hydrogels (0.36±0.04%ID/μg DNA; n=4, p< 0.05); in vivo 99m Tc uptake of encapsulated CDCs at 1hr was 2.4fold higher than transplantation of suspended CDCs. Hydrogels boosted acute cell retention following intra-myocardial transplantation (hydrogel: 92±3%; suspended cells: 15±5%), in vivo BLI revealed CDC proliferation (20%increase) in hydrogels and cell loss (99% decrease; n=3, p <0.05) in the suspended cell group. Echocardiogram revealed increased in LVEF of 0.69±1.9% in control, 10.33±2.1% in epicardial HA:Ser and 12.9±4.1% in intra-myocardial HA:Ser (n=7, p <0.05) at d28 compared to d1 post-MI. Hydrogels also induced 5fold higher angiogenesis than controls. In conclusion, HA:Ser hydrogels can be injected intramyocardially or applied epicardially as patches to beating hearts. These hydrogels induce rapid stem cell attachment, acute retention, in vivo proliferation and improve cardiac function following myocardial infarction.