Delayed wound healing in diabetes is aggravated by chronic inflammation and impaired keratinocyte migration. Although zinc facilitates skin wound healing, its excessive accumulation may induce cytotoxicity. This study explores the synergistic potential of zinc and the GPR39 agonist TC-G-1008 in enhancing diabetic wound repair. In vitro , cotreatment reduced lipopolysaccharide-induced pro-inflammatory cytokine expression and promoted keratinocyte migration. In vivo , a hydrogel incorporating zinc oxide nanoparticles and TC-G-1008 accelerated wound closure in diabetic mice and suppressed interleukin-1β expression. Notably, TC-G-1008 alone enhanced keratinocyte migration under diabetic conditions, highlighting its critical role in modulating inflammation. These findings support a zincsparing therapeutic approach using GPR39 activation to restore wound healing in diabetic settings.

Introduction
Materials and Methods
    1. Reagents
    2. Cell culture
    3. Cell viability assessment
    4. In vitro scratch test
    5. Transwell migration assay
    6. Quantitative real-time PCR
    7. Animal study
    8. T2DM induction
    9. Hydrogel preparation
    10. In vivo wound healing assay
    11. Statistical analysis
Results
    1. Non-cytotoxic dose optimization of zinc andTC-G-1008
    2. Suppression of LPS-induced inflammation by zincand TC-G-1008
    3. Promotion of keratinocyte migration
    4. Enhanced diabetic wound healing withzinc/TC-G-1008 hydrogel
    5. Inflammation reduction and skin repair bytherapeutic hydrogel
Discussion
Funding
Conflicts of Interest
Supplementary Data
References

• Kyung Mi Woo(Department of Molecular Genetics, Dental Research Institute, School of Dentistry, Seoul National University, Seoul 08826, Republic of Korea, Department of Pharmacology and Dental Therapeutics, School of Dentistry, Seoul National University, Seoul 08826, Republic of Korea) Corresponding author
• Jeong-Hwa Baek(Department of Molecular Genetics, Dental Research Institute, School of Dentistry, Seoul National University, Seoul 08826, Republic of Korea, Department of Pharmacology and Dental Therapeutics, School of Dentistry, Seoul National University, Seoul 08826, Republic of Korea)
• Jinu Lee(Department of Molecular Genetics, Dental Research Institute, School of Dentistry, Seoul National University, Seoul 08826, Republic of Korea)