Dynamic Loading Does Not Interfere With the Initial Repopulation of Decellularized Tendons: An Ex Vivo Study

Rupture of the anterior cruciate ligament (ACL) is a common injury resulting in joint instability. Tendon autografts, the gold standard to reconstruct a ruptured ACL, contain dead or dying cells upon implantation that can initiate early localized catabolic and inflammatory events. This is hypothesized to contribute to detrimental remodeling, which may compromise graft stability and increase the risk of rupture. To address this, we propose using decellularized grafts. However, the cells used to reseed decellularized tendons cannot be detected anymore in vivo, potentially due to the dynamic loading conditions. Therefore, the repopulation efficiency of decellularized tendons under dynamic load was investigated using a custom developed bioreactor. As a proof of concept, human gracilis tendons were decellularized and reseeded with human dermal fibroblasts and cultured for 7 days dynamically (2%-6% strain at 1 Hz for 7 h a day) or statically. Thereafter, the viability and infiltration ability of the reseeded cells were assessed. The loading protocol used in this study demonstrated that the bioreactor could measure the transient response of tendon mechanical behavior and could detect changes in mechanical properties over time. The application of dynamic load to reseeded decellularized tendons had no significant effect on cell adhesion, viability, cell metabolism, and infiltration. In both loading groups, cell infiltration was localized rather than globally observed. As bioreactors can serve as an in vitro or ex vivo model to potentially predict in vivo outcomes, this bioreactor shows promising potential for future ACL graft research.