A Combined Theoretical-Experimental Paradigm for Studying Mechanical Conditioning of Tissue Engineered Arteries

Abstract

There is a great unmet clinical need to develop small diameter tissue engineered blood vessels (TEBV) with low thrombogenicity and immune response, suitable mechanical properties, and a capacity to remodel to their environment [2, 3]. Development of a clinically useful small diameter TEBV will surely rely on techniques from a wide variety of disciplines, ranging from molecular and cell biology and biochemistry to material science and biomechanics. With regard to the latter, biomechanical stimuli, such as cyclic strain, have been shown to stimulate remodeling of collagen gel-derived TEBVs to greatly improve their mechanical behavior [5]. In native blood vessels, remodeling mechanisms appear to be aimed towards maintaining the local, 3-D mechanical environment (i.e., the local stresses or strains). It is becoming increasingly obvious that tissue engineered constructs also adapt to altered mechanical loading, and specific combinations of multidirectional loads appear to have a synergistic effect on the remodeling. Tissue engineered heart valve constructs exposed to cyclic flexure and shear stress, for example, exhibit a five-fold increase in production of extracellular matrix (ECM) constituents compared to constructs exposed to cyclic flexure or shear stress alone [1]. A critical gap remains, however, in understanding the role of both unidirectional and multidirectional loading on TEBV remodeling. Towards this end, we have developed theoretical and experimental frameworks to study remodeling of collagen and fibrin gel-derived TEBVs.