Potential of Chitosan-Based Systems Integrating Therapeutic Ions, Mesoporous Silica and SPIONs as Next-Generation Multifunctional Platforms for Diabetic Wound Healing

Abstract

Diabetes impairs multiple stages of the wound-healing process, resulting in chronic, infection-prone wounds that pose a substantial clinical burden. Despite available therapeutic options, effective management remains challenging owing to inadequate treatment efficacy, increasing antimicrobial resistance, and potential adverse side effects. Diabetic wounds exhibit a complex pathological microenvironment characterized by persistent bacterial colonization, hyperglycemia, tissue hypoxia, chronic inflammation, excessive matrix metalloproteinase activity, oxidative stress, and pH dysregulation. Nonetheless, traditional treatment strategies continue to rely largely on passive protection, inadequately addressing the underlying biological mechanisms responsible for impaired healing. Chitosan (CS), a naturally occurring cationic polysaccharide with high biocompatibility, antimicrobial activity, hemostatic properties, and a chemically tuneable structure, represents an attractive platform for advanced wound dressings. This review explores the potential of engineered chitosan-based systems for diabetic wound management through the strategic integration of therapeutic ions (Cu2+, Zn2+, Mg2+, Ag+, Mn2+), mesoporous silica nanocarriers, and superparamagnetic iron oxide nanoparticles (SPIONs). Unlike previous reviews that have primarily examined these components individually, the present work provides the first comprehensive analysis of their integration within a single multifunctional chitosan-based platform. By systematically evaluating their complementary therapeutic and diagnostic functions, including antimicrobial activity, angiogenic stimulation, oxidative stress modulation, controlled therapeutic delivery, and magnetic field-responsive behavior, this review establishes a unified design framework for the development of next-generation chronic wound dressings. Furthermore, it identifies potential synergistic interactions, key translational challenges, and future research directions required for the development of clinically relevant smart systems. Collectively, this integrated strategy offers a promising approach to overcoming the complex biological barriers that hinder diabetic wound healing.