Intrinsic Repair Capacity of Resident Tendon Cells is Dependent on Hole Size in an Ex Vivo Model of Laser-Induced Microdamage

Abstract

While it is generally accepted that tendon healing following widespread extracellular matrix trauma is limited, tenocytes are thought to have the capacity to repair small amounts of microdamage generated through activities of daily living. Despite this, few studies have directly studied the mechanisms governing this process. To address this, we developed a tunable in vitro model of extracellular matrix microdamage in live tendon explants that enables us to track both clearance of denatured collagen microdamage and closure of a micro-sized defect in the tendon matrix. The purpose of this study was to controllably induce varying levels of localized microdamage to the tendon explants and identify (1) if thresholds for healing exist and (2) whether repair mechanisms are dependent on initial damage size. We found that within three weeks, all tendon explants were able to clear damaged matrix to some extent regardless of the damage size. Interestingly, larger 5 mJ and 10 mJ injuries resulted in a more robust rate of damaged matrix clearance in the later weeks, while smaller injuries exhibited a more consistent rate that led to full clearance in two explants. Greater than 50% clearance of denatured collagen microdamage was typically associated with an accompanying closure of the ECM defect, suggesting a strong relationship between clearance and closure. Overall, our work demonstrates the power of our laser-induced microdamage model, which enables the direct visualization of microdamage responses. This model will be a powerful asset for investigating mechanisms of damage accumulation and/or healing, as well as identifying local tendon-specific factors that can be leveraged for therapeutics.