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

Jianyang Zhao1,2,3,4, Yuan Hu1,2,3,4, Caikun Liu1,2,3,4

  • 1School of Biomedical Sciences and Engineering, Guangzhou International Campus, South China University of Technology, Guangzhou, P. R. China.

Insights

A novel organoselenium hydrogel (TCOH) effectively treats diabetic wounds by restoring redox balance and reprogramming the immune microenvironment. This promotes faster healing and tissue regeneration, offering a new therapeutic approach for chronic diseases.

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.