Redox-Regulating Propolis- and Honey-Containing Hydrogels in Osteoarthritis

Oxidative stress and persistent inflammation are central mechanisms in osteoarthritis (OA), contributing to chondrocyte dysfunction, mitochondrial impairment, extracellular matrix degradation, pain-related signaling, and progressive joint tissue remodeling. Reactive oxygen species (ROS) act not only as damaging agents but also as regulators of redox-sensitive inflammatory pathways, including NF-κB, MAPK, and Nrf2-related antioxidant responses. Accordingly, localized strategies capable of modulating the oxidative-inflammatory microenvironment may offer therapeutic advantages over non-targeted antioxidant approaches. This review summarizes current evidence on natural hydrogel-based systems containing propolis and honey as potential redox-modulating and anti-inflammatory platforms for OA-related tissue degeneration. Propolis and honey are bee-derived bioactive products rich in polyphenols and other redox-active compounds with antioxidant, anti-inflammatory, antimicrobial, and tissue-protective properties. Their incorporation into hydrogel matrices may support sustained local delivery, improved tissue retention, and stimulus-responsive release within inflamed or oxidatively stressed tissues. Particular attention is given to mechanisms involving ROS regulation, suppression of inflammatory mediators, activation of endogenous antioxidant defenses, and protection of cartilage extracellular matrix. Current formulation evidence is also critically interpreted according to its disease specificity, distinguishing direct OA/cartilage-related evidence from indirect wound healing and tissue repair data. The review also addresses intra-articular biomechanical requirements, enzyme-responsive degradation, immunological safety, formulation standardization, and translational barriers.