Physiologic compliance in engineered small-diameter arterial constructs based on an elastomeric substrate

Compliance mismatch is a significant challenge to long-term patency in small-diameter bypass grafts\ud because it causes intimal hyperplasia and ultimately graft occlusion. Current engineered grafts are\ud typically stiff with high burst pressure but low compliance and low elastin expression. We postulated\ud that engineering small arteries on elastomeric scaffolds under dynamic mechanical stimulation would\ud result in strong and compliant arterial constructs. This study compares properties of engineered arterial\ud constructs based on biodegradable polyester scaffolds composed of either rigid poly(lactide-co-glycolide)\ud (PLGA) or elastomeric poly(glycerol sebacate) (PGS). Adult baboon arterial smooth muscle cells (SMCs)\ud were cultured in vitro for 10 days in tubular, porous scaffolds. Scaffolds were significantly stronger after\ud culture regardless of material, but the elastic modulus of PLGA constructs was an order of magnitude\ud greater than that of porcine carotid arteries and PGS constructs. Deformation was elastic in PGS\ud constructs and carotid arteries but plastic in PLGA constructs. Compliance of arteries and PGS constructs\ud were equivalent at pressures tested. Altering scaffold material from PLGA to PGS significantly decreased\ud collagen content and significantly increased insoluble elastin content in constructs without affecting\ud soluble elastin concentration in the culture medium. PLGA constructs contained no appreciable insoluble\ud elastin. This research demonstrates that: (1) substrate stiffness directly affects in vitro tissue development\ud and mechanical properties; (2) rigid materials likely inhibit elastin incorporation into the extracellular\ud matrix of engineered arterial tissues; and (3) grafts with physiologic compliance and significant\ud elastin content can be engineered in vitro after only days of cell culture