Variation of cyclic strain parameters regulates development of elastic modulus in fibroblast/substrate constructs

Dynamic mechanical culture systems are a widely studied approach for improving the functional mechanical properties of tissue engineering constructs intended for loading-bearing orthopedic applications such as tendon/ligament reconstruction. The design of effective mechanical stimulation regimes requires a fundamental understanding of the effects of cyclic strain parameters on the resulting construct properties. Toward this end, these studies employed a modular cyclic strain bioreactor system and fibroblast-seeded, porous polyurethane substrates to systematically investigate the effect of varying cyclic strain amplitude, rate, frequency, and daily cycle number on construct mechanical properties. Significant differences were observed in response to variation of all four loading parameters tested. In general, the highest values of elastic modulus within each experimental group were observed at low to intermediate values of the experimental variables tested, corresponding to the low to subphysiological range (2.5% strain amplitude, 25%/s strain rate, 0.1-0.5 Hz frequency, and 7,200-28,800 cycles/day). These studies demonstrate that fibroblasts are sensitive and responsive to multiple characteristics of their mechanical environment, and suggest that systematic optimization of dynamic culture conditions may be useful for the acceleration of construct maturation and mechanical function.