We postulate that immobilization of tyramine-substituted hyaluronan (THA) into an extracellular matrix (ECM) scaffold may be a strategy to promote an anti-inflammatory response to the ECM. Further, we posit that the implantation site could influence the inflammatory response and remodeling of an ECM scaffold. Eight beagles underwent implantation of fascia ECM grafts, treated with either immobilized low molecular weight (57 kDa) THA or water only, in both the shoulder injury and body wall sites. Dogs were euthanized at 12 weeks and fascia grafts harvested en bloc for histology. Grafts implanted at the body wall had significantly higher inflammatory cell infiltrate and vascularity, and significantly lower retardance (collagen density), than grafts at the shoulder, suggestive of a more intense, persistent, and perhaps degradative inflammatory and remodeling response at the body wall than shoulder injury site in the canine model. However, the presence of immobilized low MW THA had no effect on the inflammation response or remodeling of fascia ECM compared to water-treated controls. Importantly, these results suggest that the inflammatory response and remodeling of biomaterial implants depends on the location of implantation and therefore our animal models need to be carefully chosen. Further, the potential anti-inflammatory advantages of hyaluronan (HA) in wound healing do not appear to be realized when presenting it to the host as non-degradable hydrogel even if its capacity for binding HA binding protein is maintained. Further study treating ECM with uncross-linked (free) HA or immobilized low MW THA as a means to deliver free HA or other biomolecules to a surgical repair site is warranted.