Nano-enzyme functionalized hydrogels promote diabetic wound healing through immune microenvironment modulation

Area of Science:

• Biomaterials Science
• Regenerative Medicine
• Wound Healing Research

Background:

• Diabetic wounds present significant challenges, often leading to amputation due to impaired healing.
• Key issues in diabetic wounds include M1 macrophage accumulation and heightened oxidative stress.
• Current treatments often fall short in addressing the complex pathophysiology of these wounds.

Purpose of the Study:

• To engineer a novel nano-enzyme functionalized hydrogel, GelMA@Mg-POM, for enhanced diabetic wound healing.
• To investigate the therapeutic potential of GelMA@Mg-POM in addressing M1 macrophage accumulation and oxidative stress.
• To evaluate the efficacy of GelMA@Mg-POM in promoting cellular regeneration and improving the wound microenvironment.

Main Methods:

• Fabrication of a GelMA hydrogel incorporating magnesium ion-doped molybdenum-based polymetallic oxide (Mg-POM) nano-enzymes.
• UV crosslinking to create a porous three-dimensional hydrogel structure.
• In vitro and in vivo assessments of cell behavior, inflammatory markers, and tissue regeneration in diabetic wound models.

Main Results:

• GelMA@Mg-POM significantly boosted human umbilical vein endothelial cell (HUVEC) migration and proliferation.
• The hydrogel effectively scavenged reactive oxygen species (ROS) and modulated the inflammatory milieu.
• Macrophage reprogramming from M1 to M2 phenotype was observed, alongside enhanced angiogenesis and collagen deposition in vivo.
• In vivo studies in diabetic rats showed improved granulation tissue formation and collagen production.

Conclusions:

• The GelMA@Mg-POM system demonstrates potent capabilities in enhancing diabetic wound healing.
• This novel biomaterial effectively addresses key pathological features, including inflammation and oxidative stress.
• GelMA@Mg-POM shows considerable promise as an advanced therapeutic agent for non-healing diabetic wounds.