Living Microecological Microneedle Patches Enable Proregenerative Microenvironmental Remodeling for Promoting...

Area of Science:

• Biomaterials Science
• Regenerative Medicine
• Wound Healing

Background:

• Diabetes mellitus impairs wound healing due to chronic inflammation, hypoxia, and infection risk.
• Existing treatments often fall short in addressing the complex microenvironment of diabetic wounds.

Purpose of the Study:

• To develop and evaluate a living microecological microneedle patch (LMMP) for promoting infected diabetic wound (IDW) healing.
• To investigate the mechanisms by which LMMP, containing Chlorella (Chl), gallic acid (GA), and modified chitosan/hyaluronic acid, remodels the wound microenvironment.

Main Methods:

• Fabrication of LMMPs by integrating Chl-loaded hyaluronic acid (HA) microneedles onto gallic acid (GA)-functionalized carboxymethyl chitosan (CMC)-oxidized hyaluronic acid (OHA) sheets.
• In vivo assessment of LMMP efficacy in accelerating the healing of nonhealing IDWs.
• Investigation of LMMP's effects on hypoxia, inflammation, bacterial infection, and tissue regeneration signaling pathways (MAPK, PI3K/AKT, HO-1).

Main Results:

• LMMPs effectively delivered therapeutic agents and adhered to IDWs.
• Chlorella-derived oxygen relieved hypoxia, activating MAPK and PI3K/AKT pathways for regeneration and vascularization.
• GA reprogrammed M1 macrophages to M2 phenotypes, reducing inflammation, while CMC exhibited antimicrobial activity against virulent microbes.
• LMMP treatment significantly accelerated the healing of nonhealing IDWs in vivo.

Conclusions:

• The developed LMMP is a promising therapeutic strategy for infected diabetic wound healing.
• LMMP effectively remodels the pathological microenvironment of IDWs by addressing hypoxia, inflammation, infection, and promoting regeneration.
• This approach offers a potential clinical solution for improving outcomes in patients with nonhealing diabetic wounds.