Emerging Nanomaterials Can Even Treat Chronic Wounds: A Review of Evidence on Magnesium-Based Systems

Abstract: Chronic wounds remain a severe clinical challenge worldwide due to persistent inflammation, impaired tissue regeneration, and refractory infection control. Recently, magnesium-based materials have garnered tremendous attention for chronic wound healing owing to their exceptional biocompatibility, biodegradability, and multifaceted biological functions in remodeling the wound immune microenvironment. Well-established preclinical evidence demonstrates that magnesium and its derivatives facilitate chronic wound repair by regulating inflammatory responses, promoting angiogenesis, enhancing cellular proliferation and migration, and exerting antibacterial effects, thus constructing a favorable microenvironment for tissue regeneration. Emerging (though still partly speculative) findings suggest that degradation products of magnesium, particularly Mg 2 ⁺ ions, play a central role in directing immune cell polarization, optimizing endothelial cell activity, and alleviating oxidative stress. Magnesium-based inorganic materials, nanostructured systems, and hybrid platforms integrated with hydrogels or other bioactive components also exhibit outstanding preclinical therapeutic potential. It is important to note that the vast majority of current evidence remains at the preclinical stage, and any interpretation of translational readiness should be made with caution. However, the clinical translation of these materials is still severely restricted by multiple bottlenecks: the lack of precise control over magnesium degradation and Mg 2 ⁺ release kinetics, safety risks arising from local pH elevation and hydrogen gas generation, deficient long-term toxicological data, and the absence of standardized evaluation systems for magnesium-based wound dressings. Future research should prioritize the development of tunable and stimuli-responsive delivery systems, deepening mechanistic insights into magnesium-mediated immunomodulation, and incorporating advanced manufacturing technologies to realize personalized therapeutic strategies. Rigorous biosafety evaluations and clinically relevant preclinical models are also imperative. In conclusion, magnesium-based materials stand as a highly promising and versatile strategy for chronic wound repair, holding great potential to be developed as multifunctional platforms that integrate antibacterial, immunoregulatory, and tissue-regenerative properties for clinical translational applications. Keywords: magnesium-based materials, drug delivery, wound healing, biomaterials, chronic wound healing