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Updated: Jul 12, 2026
A Protocol for Constructing a Rat Wound Model of Type 1 Diabetes
Published on: February 17, 2023
Metal ion-based therapeutic strategies for diabetic wound healing: Mechanisms, biomaterial platforms, and
Yue Xiong1, Chao He2, Dandan Su3
1Department of Pharmacy, The Eighth Affiliated Hospital, Sun Yat-sen University, 3025 Shennan Middle Road, Shenzhen, 518033, China; State Key Laboratory of Neurology and Oncology Drug Development, Jiangsu, 10070, China.
Abstract:
The management of chronic diabetic wounds remains a persistent clinical challenge, characterized by prolonged healing times and high recurrence rates. These wounds typically stall in the inflammatory phase due to multiple overlapping pathological factors, including multidrug-resistant infections, poor microvascular networks, sustained oxidative stress, and impaired immune responses. Traditional single-target treatments struggle to overcome these concurrent barriers; thus, there is a pressing need for multifunctional therapeutic approaches. Metal ions (evolutionarily conserved enzymatic cofactors and redox mediators) provide this mechanistic versatility by coordinating antimicrobial defense, angiogenesis, inflammation resolution, and tissue remodeling through distinct yet complementary pathways. We systematically examine the specific mechanisms of nine functional metal ions (Ag+, Cu2+, Zn2+, Au3+, Ce3+/Ce4+, Mg2+, Ca2+, Mn2+, and Co2+), and discuss recent advances in bimetallic synergistic platforms (e.g., Fe-Cu, Cu-Ce). To connect biological potential with practical application, we compare diverse delivery architectures (such as stimuli-responsive hydrogels, metal-organic frameworks, electrospun nanofibers, and microneedle patches) focusing on their release kinetics and structural advantages. Finally, we address the primary bottlenecks limiting clinical translation, notably protein corona formation, and outline future directions for designing the next generation of safe, smart, and highly effective metal-based wound dressings.
Insights
Metal ions offer a versatile solution for chronic diabetic wounds by addressing multiple healing barriers. Advanced delivery systems enhance their efficacy, paving the way for improved wound care treatments.
Area of Science:
- Biomaterials Science
- Nanotechnology
- Wound Healing Research
Background:
- Chronic diabetic wounds present significant clinical challenges due to prolonged healing and high recurrence.
- Pathological factors like infection, poor vascularization, oxidative stress, and immune dysfunction impede healing.
- Current single-target treatments are insufficient for these complex wounds, necessitating multifunctional approaches.
Purpose of the Study:
- To systematically review the mechanisms of nine functional metal ions in wound healing.
- To explore advances in bimetallic synergistic platforms and novel delivery systems for metal ions.
- To identify challenges and future directions for metal-based wound dressings.
Main Methods:
- Systematic examination of metal ion mechanisms (Ag+, Cu2+, Zn2+, Au3+, Ce3+/4+, Mg2+, Ca2+, Mn2+, Co2+).
- Review of bimetallic synergistic platforms (e.g., Fe-Cu, Cu-Ce).
- Comparison of diverse delivery architectures (hydrogels, MOFs, nanofibers, microneedles).
Main Results:
- Metal ions exhibit multifaceted roles in antimicrobial defense, angiogenesis, inflammation resolution, and tissue remodeling.
- Bimetallic platforms and advanced delivery systems show promise for enhanced therapeutic effects.
- Protein corona formation is a key challenge for clinical translation.
Conclusions:
- Metal ions provide a versatile therapeutic strategy for chronic diabetic wounds.
- Innovative delivery systems are crucial for optimizing metal-based wound dressings.
- Further research is needed to overcome clinical translation barriers and develop next-generation wound care solutions.
