Effect of Physiologic Oscillatory Fluid Shear Stress on Engineered Heart Valve Tissue Formation.

It was previously demonstrated that combined flexure and flow in vitro conditioning augments engineered heart valve tissue formation using bone marrow-derived mesenchymal stem cells (MSC) seeded on polyglycolic acid (PGA)/poly-L-lactic acid (PLLA) blend nonwoven fibrous scaffolds (Engelmayr, et al., Biomaterials 2006; vol. 27 pp. 6083-95). Additionally, seeded scaffolds incorporated into a tissue engineered valve construct experienced significant increases in tissue formation rates with media supplementation (basic fibroblast growth factor [bFGF] and ascorbic acid-2-phosphate [AA2P]) and dynamic conditioning approximating pulmonary valve levels (Ramaswamy, et al., Biomaterials 2010; vol. 31 pp. 1114-1125). CFD studies have since shown extensive similarities between flow patterns in flexure flow specimens and those conditioned in a tri-leaflet valve geometry. Most notably, highly oscillatory surface shear stresses are evident both on the inner surface of flexure, flow samples and the arterial surface of the valve construct. Given the fact that the scaffolds underwent only modest strains (approximately 7% max) during either flexure flow or physiological conditioning, the oscillatory surface shear stresses estimated in both studies may play a substantial role in eliciting MSC collagen production in the highly dynamic engineered heart valve fluid mechanical environment. Through a newly designed bioreactor, capable of simultaneously applying physiologically relevant levels of flexure, stretch and flow (FSF) the effect of oscillatory shear on tissue formation will be isolated and investigated.