Sulfated hyaluronic acid for wound repair: Mechanisms, materials, and translational challenges

Sulfated hyaluronic acid (sHA) is emerging as a promising biomaterial for advanced wound dressings because it combines the intrinsic biocompatibility and extracellular matrix (ECM)-like hydration of hyaluronic acid (HA) with added chemical functionality that enhances stability and bioactivity. Chronic wounds, particularly diabetic ulcer, -remain a major clinical challenge due to persistent inflammation, protease/reactive oxygen species (ROS)-rich microenvironments, impaired angiogenesis, and poor growth-factor retention; native HA is limited by rapid enzymatic degradation, low protein affinity, and potentially pro-inflammatory low-molecular fragments, motivating strategies to introduce sulfate groups onto HA to tune its interactions with cells and proteins. In this review, we performed a comprehensive literature review of the biological functions and applications of sHA in wound healing. Key results demonstrate that sHA significantly enhances anti-inflammatory responses, promotes sustained release of cationic therapeutics, improves angiogenesis, and reduces fibrosis. Furthermore, sHA-functionalized hydrogels accelerate diabetic wound healing by modulating macrophage polarization, enhancing re-epithelialization, and supporting vascularization. In further, we also offered a practical roadmap for researchers and clinicians to rationally design next-generation sHA-based dressings with improved reproducibility, controlled release, and safety.