Tissue-Conforming Organoselenium Hydrogel with Microphase-Controlled Acylhydrazone Crosslinking Kinetics Expedites...

Area of Science:

• Biomaterials Science
• Regenerative Medicine
• Wound Healing

Background:

• Diabetic wounds exhibit a pathological microenvironment characterized by oxidative stress, advanced glycation end-products (AGEs), and chronic inflammation, hindering healing.
• Existing antioxidant hydrogels lack conformability, compromising therapeutic agent delivery and failing to address the interconnected pathological processes in diabetic wounds.

Purpose of the Study:

• To synthesize a tissue-conforming organoselenium hydrogel (TCOH) with extended crosslinking kinetics for effective diabetic wound management.
• To investigate the TCOH's ability to restore redox homeostasis, enhance angiogenesis, and modulate the immune microenvironment.

Main Methods:

• Synthesis of an organoselenium polymer (OSP) enabling microphase-separation and extended acylhydrazone crosslinking.
• In vitro and in vivo evaluation of TCOH's therapeutic effects on diabetic wound healing.
• Transcriptomic profiling and Western Blot analysis to assess molecular signaling pathways (AGE-RAGE, NF-κB) and metabolic profiles.

Main Results:

• TCOH demonstrated effective conformability to wound geometries, delivering organoselenium motifs to the wound bed.
• TCOH successfully restored redox homeostasis, promoted M2 macrophage polarization, and enhanced angiogenesis.
• Suppression of AGE-RAGE and NF-κB signaling pathways and restoration of glycolipid metabolism were confirmed, leading to accelerated wound closure and tissue regeneration.

Conclusions:

• The developed TCOH offers a promising therapeutic platform for diabetic wound healing by dynamically adapting to tissue and regulating multiple pathological pathways.
• This approach represents a new paradigm in chronic wound management, with potential applications for other redox- and AGE-related chronic diseases.