Development of low-molecular-weight polysaccharide-based wound dressings for full-thickness cutaneous wound healing via coacervate formation

The development of polysaccharide-based wound dressings that are easy to prepare, adhere to tissue, adapt to diverse shapes and exhibit tunable mechanical properties holds significant clinical interest. This study introduced a simple spontaneous liquid-liquid phase separation technique employing low-molecular-weight and high polyion concentration of chitosan (CS) and hyaluronic acid (HA) to fabricate CS/HA coacervates. Upon increasing the molecular weight of chitosan from 7 kDa to 250 kDa, a transition in the CS/HA coacervates from liquid-like state to an elastic liquid and eventually to a solid-like state was observed. The resulting CS/HA coacervates demonstrated robust water resistance and adhesion to skin tissue. Notably, the molecular weight of chitosan significantly influenced the mechanical properties and hydration levels of the CS/HA coacervates. Moreover, in vivo studies using a full-thickness cutaneous defect model revealed that the CS/HA coacervates, prepared using 100 kDa chitosan, markedly accelerate wound healing. The coacervates' ease of preparation, wet adhesion, heterogeneous structure, suitability for irregularly shaped wounds, and exceptional wound healing promotion of the coacervates qualify them as an optimal wound dressing.