Abstract P180: Tunable Elastin-like Protein-based Hydrogels For Cell Transplantation In Vascular Repair

Introduction: Endothelial cells can improve blood perfusion in diseased blood vessels; however, direct injection of cells significantly decreases their survival and functionality for angiogenesis. To address these limitations, we study a family of engineered extracellular matrices with tunable biochemical and biomechanical cues for enhanced survival and improved angiogenic behavior of ECs. Materials & Methods: Engineered hydrogels, termed ELP-PEG, consists of two components of a hydrazine-modified elastin-like protein (ELP-HYD) and an aldehyde- or benzaldehyde-modified, polyethylene glycol (PEG-ALD or PEG-BZA), which interact with each other through hydrazone dynamic covalent chemistry (DCC) bonds to form ELP-PEG hydrogels. Stiffness is controlled by altering the number of PEG-ALD or PEG-BZA crosslinks, and the stress relaxation rate is tuned by varying the PEG-ALD crosslinks vs. PEG-BZA. Stiffness and stress relaxation rates of the hydrogels were assessed by dynamic oscillatory rheology. Afterward, human umbilical vein endothelial cells (HUVECs) were encapsulated within gels to assess cell viability and spreading using a Live/Dead Cytotoxicity assay and confocal fluorescence imaging. Results and Discussion: Stress relaxation rate in ELP/PEG-ALD is much slower compared with a similar combination in ELP/PEG-BZA. Rheology measurements of the RGD-ELP/PEG (2%/2%) hydrogels demonstrated a storage modulus of 800Pa. It confirms the tunability of the stress relaxation rate with constant stiffness. Cell viability assay demonstrated that both hydrogels could support high cell viability (>90%) for 7 days. After 7 days, cell spreading increased in RGD-ELP/PEG-BZA hydrogels, however, cells did not form elongated morphology in RGD-ELP/PEG-ALD hydrogels, suggesting that stress relaxation rate and mechanical stiffness are key characteristics in modulating endothelial cell behavior. Conclusions: ELP/PEG-ALD/BZA promotes the angiogenic behavior of endothelial cells and is a promising candidate for cell delivery in vascular diseases.