Drug-loaded hyaluronic acid hydrogel as a sustained-release regimen with dual effects in early intervention of tendinopathy

Resulting from accumulative microtrauma, impaired healing and oxidative stress, tendinopathy is a debilitating and relentlessly deteriorating disease that greatly affects daily function and quality of life. Current therapy usually provides symptomatic relief only. Sufferers undergo repetitive and protracted treatment courses that rarely alter the disease process. We aim to develop a sustained-release regimen with an intrinsic therapeutic effect in tendinopathy treatment, using oxidised hyaluronic acid/adipic acid dihydrazide hydrogel (HA hydrogel) as both the drug carrier and a mitigating agent of symptoms. We show that HA hydrogel can mitigate tendinopathy changes both in vitro (mechanically induced tendinopathy model) and in vivo (collagenase-induced tendinopathy model). A potent anti-oxidative (pigallocatechin gallate) incorporated into HA hydrogel conferred an additional protective effect in both models. The results indicate that when administered early, combined medications targeting different pathogenesis pathways can resolve tendinopathy. Although facilitating the healing process and mitigating oxidative stress are promising therapeutic strategies, the most effective regimen for tendinopathy treatment has to be determined yet. The established experimental model and drug carrier system provide a platform for exploring new therapeutics against this debilitating disease.