Rotator cuff tendon injury is a debilitating health concern that affects more than 40% of the aging population. Despite advances in surgical treatment, the failure rate of rotator cuff repairs ranges 20-90%. Naturally-occurring extracellular matrices (ECMs) have been recently investigated as augmentation scaffolds, but none has yet demonstrated both the appropriate biological and mechanical properties.
This dissertation proposes to enrich fascia ECM with high molecular weight tyramine substituted-hyaluronan (TS-HA) for rotator cuff repair. The central hypothesis is that TS-HA treatment will decrease chronic inflammation without decreasing the time-zero or post-implantation mechanical properties of fascia. The specific aims are to develop a TS-HA treatment method and to evaluate the host response and concomitant mechanical properties of treated fascia in a rat abdominal wall model.
TS-HA treatment increased the HA content of fascia by an order of magnitude to ~1% tissue weight. The incorporated HA was distributed throughout the ECM and, upon cross-linking, was retained as a hydrogel network. Cross-linked TS-HA treated fascia exhibited an increased macrophage and giant cell response and a lower density of fibroblast-like cells than water treated controls. Treated fascia, with or without cross-linking, exhibited a predominantly M2 pro-remodeling macrophage profile similar to water controls, which is suggestive of constructive tissue remodeling. All grafts exhibited a chronic lymphocytic response that is suggestive of an immune response to the fascia xenograft. Fascia samples in all groups demonstrated time-dependent decreases in mechanical properties. Cross-linked TS-HA treated fascia exhibited a lower toe-region elastic modulus and trended towards a higher transition strain than water treated controls not only after implantation, but also at time zero.
These findings demonstrate that HA augmentation can alter both the host response and the mechanical properties of fascia ECM. Contrary to the hypothesis, the particular TS-HA treatment (at the concentration, molecular weight, and tyramine substitution rate) employed in this dissertation elicited a heightened macrophage and giant cell response and a decrease in low-load elastic mechanical properties compared to water treated fascia. This work provides a starting point and guidance for the ongoing development of TS-HA enriched fascia ECM as an augmentation scaffold for rotator cuff repair.