Engineered multifunctional nanocomposite hydrogel dressing to promote vascularization and anti-inflammation by sustained releasing of Mg2+ for diabetic wounds

Abstract

Diabetic ulcers are common and severe chronic wound. For the treatment of diabetic ulcers, due to the existence of sinus and fistula in the wound sites, the prefabricated hydrogel could not cover the deep wounds well and result in further presence and proliferation of bacteria at the deep wound site, which increases the risk of secondary infection. In addition, most current hydrogel dressings do not rapidly repair wounds due to the lack of bioactivity. Therefore, it's essential to develop a bioactive hydrogel dressing with self-adaption to solve the above clinical problems. In this work, HQ hydrogel was fabricated by the self-crosslinking of hyaluronic acid modified with phenyl boronate acid (HA-PBA) by boronate ester dynamic bonds and electronic interaction between quaternized chitosan (QCS) and HA-PBA, which possessed good injectability, self-healing, adhesion and antibacterial properties. Especially, HQ hydrogel with good self-adaption can be shaped as needed and automatically adapt to the wounds with all kinds of shapes. In addition, Magnesium-containing bioactive glasses (BGs) with a uniform spherical morphology and amorphous structure were incorporated into HQ hydrogel to achieve nanocomposite hydrogel (HQB), which possessed good bioactivity and could slowly release magnesium to recruit cells, promote vascularization and anti-inflammation. More importantly, animal experiments showed that HQB hydrogel can strikingly accelerate wound healing of diabetic SD rats by improving granulation tissues formation, collagen deposition, the formation of blood vessels and decreasing inflammation in the wound sites, indicating a good clinical application prospect as wound dressing for diabetic wound healing.