Effects of Defined Biochemical Stimuli on Smooth Muscle Cell Differentiation in Tissue Engineered Vascular Grafts

摘要

While initial tissue engineered vascular grafts (TEVGs) have been encouraging, studies suggest that their long-term function will likely significantly improve if associated smooth muscle cells (SMCs) can be maintained in a differentiated phenotype. To maintain or guide TEVG SMCs to a differentiated state, a deeper understanding of the effects of specific ECM associated biochemical stimuli on cellular differentiation in 3D is required. However, the controlled exploration of the impact of ECM-associated biochemical signals in 3D on cellular differentiation has proven difficult, since most synthetic and natural tissue engineering scaffold materials adsorb a range of plasma proteins from the blood or cell culture media. These adsorbed proteins, the levels of which are highly variable and difficult to quantitate, are major determinants of cell behavior, in addition to any molecule added by the researcher. For controlled in vitro investigation of the effects of specific ECM biochemical stimuli on SMC differentiation, we have therefore selected poly(ethylene glycol) diacrylate (PEGDA) as a scaffold material. PEGDA is essentially “non-biofouling”, presenting a biochemical ”blank slate” to cells in the absence of biochemical modification, but can be readily modified to contain defined levels of desired biochemical moieties due to its photoactivity.