Dynamic Flexure Independently Stimulates Engineered Heart Valve Tissue Development

The independent effect of dynamic flexure on the development of tissue engineered heart valves (TEHV) was investigated. Engineered heart valve tissues were constructed by seeding ovine smooth muscle cells onto rectangular scaffold strips and incubating the resultant constructs in a dynamic flexure bioreactor or under static conditions for three weeks. Tests indicated a trend of higher effective stiffness, increased collagen accumulation (p<0.05), improved mid-thickness cellularity, and increased expression of vimentin in flexed vs. static samples, with comparable levels of glycosaminoglycan accumulation and alphaactin expression. These results suggest that dynamic flexural stimulation can independently reproduce certain aspects of TEHV development observed in pulse duplicators. INTRODUCTION Pulse duplicator bioreactors have been successfully implemented to stimulate the development of tissue engineered heart valves (TEHV) [2]. Due to their coupled mechanical stimuli, however, they are not directly amenable to biomechanical studies which aim to isolate the independent effect of simple modes of mechanical stimulation. Dynamic flexure represents a simple mode of deformation experienced by TEHV during in vitro development in pulse duplicators, as well as in vivo following implantation. In order to investigate the isolated effect of dynamic flexure on the development of TEHV, we designed a bioreactor with the capacity to provide cyclic three-point bending to 12 rectangular samples of TEHV biomaterial [1]. Our previous study demonstrated that dynamic flexure leads to both quantitative and qualitative changes in the flexural mechanical properties of non-woven mesh scaffolds coated with poly-4-hydroxybutyrate (Tepha, Inc., Cambridge, MA). In the present study, we aimed to isolate the effect of dynamic flexure on the mechanical property changes due to tissue deposition from changes due to scaffold degradation. To this end, we used a scaffold that does not demonstrate a significant change in flexural mechanical properties over a three-week period. E (k Pa ) 0 200 400 600 80