Multifunctional polyphenol-based silk hydrogel alleviates oxidative stress and enhances endogenous regeneration of osteochondral defects

In osteochondral defects, oxidative stress caused by elevated levels of reactive oxygen species (ROS) can disrupt the normal endogenous repair process. In this study, a multifunctional hydrogel composed of silk fibroin (SF) and tannic acid (TA), the FDA-approved ingredients, was developed to alleviate oxidative stress and enhance osteochondral regeneration. In this proposed hydrogel, SF first interacts with TA to form a hydrogen-bonded supramolecular structure, which is subsequently enzymatically crosslinked to form a stable hydrogel. Furthermore, TA had multiple phenolic hydroxyl groups that formed interactions with the therapeutic molecule E7 peptide for controlled drug delivery. In vitro investigations showed that SF-TA and SF-TA-E7 hydrogels exhibited a multitude of biological effects including scavenging of ROS, maintaining cell viability, and promoting the proliferation of bone marrow mesenchymal stem cells (BMSCs) against oxidative stress. The proteomic analysis indicated that SF-TA and SF-TA-E7 hydrogels suppressed oxidative stress, which in turn improved cell proliferation in multiple proliferation and apoptosis-related pathways. In rabbit osteochondral defect model, SF-TA and SF-TA-E7 hydrogels promoted enhanced regeneration of both cartilage and subchondral bone as compared to hydrogel without TA incorporation. These findings indicated that the multifunctional SF-TA hydrogel provided a microenvironment suitable for the endogenous regeneration of osteochondral defects.