A Modular System to Examine Fibroblastic Differentiation of Mesenchymal Stem Cells Under Tensile Loading in Response to Changes in the Extracellular Environment

Hundreds of thousands of injuries to ligaments, tendons or the joint capsule occur in the U.S. each year, resulting in significant reduction of quality of life for many patients [1]. Existing reconstruction techniques for torn tendons/ligaments result in significant morbidity and cannot fully recapitulate the native joint biomechanics, leading to secondary degeneration over time, such as premature osteoarthritis. Thus, tissue-engineered alternatives to current grafts, potentially using stem cells in combination with an appropriate scaffold, are greatly needed. In response, our laboratory is investigating a novel hydrogel system and a custom tensile bioreactor as an in-vitro model to study the formation of both fibrous (ligament) tissue and the ligament-bone interface. In these studies, we examine the effect of tensile loading and the degradability of the surrounding environment on cellular morphology and tendon/ligament extracellular matrix (ECM) production by mesenchymal stem cells (MSCs). In particular, the response of MSCs embedded within hydrogels with varying degrees of susceptibility to degradation by collagenase is explored. In addition, proof-of-principle experiments are presented to extend this system to examine the effect of co-culture of multiple cell types on differentiation of MSCs in a milieu that mimics the bone-ligament insertion.