Our team’s research interests lie in the areas of cardiac and vascular tissue engineering, with a particular emphasis on the development and characterization of extracellular matrix (ECM) -derived biomaterials. Materials of key interest to this research are those derived from hyaluronan, a highly biocompatible and mechanically versatile glycosaminoglycan (GAG) distributed in the connective tissue matrix. The primary long-term research objective centers on the development of novel tissue engineering solutions, to prevent re-occlusion and loss of patency of small diameter blood vessels and vascular grafts following surgical intervention.The creation of endothelialized, non-thrombogenic hydrogel barriers to isolate the damaged vessel wall from blood is one potential solution to re-occlusion in small diameter arteries. Though unconventional, the use of biocompatible and non-degradable tissue-derived biomaterials (e.g., crosslinked hyaluronan hydrogels) is expected to elicit the native cellular phenotype and thus avoid the exaggerated tissue response and vascular remodeling that often occurs with the deployment synthetic cardiovascular implants. Our research activities evaluate the feasibility of the concept in an in vitro environment using crosslinked hyaluronan gels (hylans) as test materials, and will lay the groundwork for future in vivo testing of the fabricated barrier graft. Hylan gels have unique biological characteristics including low immunogenicity and antigenicity, and predictable mechanical properties. This project intends to thoroughly evaluate their suitability for use as tubular barrier grafts through demonstration of their (i) mechanical appropriateness, (ii) thromboresistence, and (iii) their ability to support a functional surface endothelium and deter intimal hyperplasia and tissue-ingrowth into the vessel lumen. The hylan graft developed in this study can potentially help to maintain long-term patency of small diameter vessels, following angioplasty. The realization of this overall research objective is thus based on strategies that (i) identify or design novel chemical derivatization and crosslinking mechanisms for the synthesis of mechanically appropriate vascular implant materials, (ii) characterize interactions between the biomaterial and vascular and blood cells with an emphasis on material -induced changes to the phenotype and genotype of healthy and distressed vascular populations, and (iii) elucidate the role of matrix molecules (e.g., elastin, GAGs) in determining the progression of vascular disease, and (iv) identify new sources of universally applicable cell-types that may be used to populate vascular implants to enhance their long-term efficacy. Summarized below are details pertaining to each of these strategies that were accomplished or initiated in the previous year.
