Microenvironmental pH modulating oxygen self-boosting microalgal prodrug carboxymethyl chitosan/hyaluronic acid/puerarin hydrogel for accelerating wound healing in diabetic rats

Abstract

Chronic diabetic wounds are characterized by a range of detrimental features, including hypoxia, elevated levels of reactive oxygen species, impaired angiogenesis, chronic inflammation, and an increased susceptibility to bacterial infections. We have developed an innovative multifunctional hydrogel system based on carboxymethyl chitosan, which incorporates embedded microalgae PCC7942 along with hyaluronic acid and puerarin, termed PCC7942@carboxymethyl chitosan/hyaluronic acid/puerarin hydrogel. It demonstrated outstanding capabilities in exudate absorption, mechanical flexibility, hemostatic action, and antibacterial efficacy. Furthermore, it effectively modulated the pH of wound microenvironment through the hydrolysis of amide bonds, thereby establishing a favorable low-pH microenvironment. Microalgae in hydrogel covered in the wound exhibited stable and continuous oxygen production within 24 h, with more efficiency in dissolved oxygen penetration through skin. Furthermore, prodrugs such as hyaluronic acid and puerarin from hydrogel displayed the controlled release behavior and facilitated the fast and enhanced accumulation of drugs at wound site, thereby accelerating the process of wound healing via enhanced angiogenesis and anti-inflammation effects. In summary, the healing-promoting effect of PCC7942@carboxymethyl chitosan/hyaluronic acid/puerarin hydrogel in type 1 diabetic rats can be attributed to the synergistic effects of microalgae, hyaluronic acid, and puerarin, which collectively accelerated wound healing rate and improved the quality of wound recovery.