Abstract
Metal-Organic Framework (MOF)/nanofiber composites represent a significant evolution in advanced wound care, offering a multi-functional platform for controlled therapeutic delivery and accelerated tissue regeneration. The superior performance of these systems is frequently reported with nearly 100% wound closure within 14 days and a broad-spectrum antimicrobial efficacy, yet the clinical translation remains contingent upon addressing technical and toxicological constraints. On the top of those constraints are the lack of long term stability data and precise dosing protocols in complex wound environments. This review provides a critical evaluation of these composites, analyzing established nanofibers impeded with zinc, copper, silver, zirconium alongside emerging iron -based MOFs that provide superior biocompatibility and enzymatic ‘chemodynamic’ activity, and cobalt systems which offer unique hypoxia-mimicking properties for angiogenesis. In this review the stability-toxicity paradox inherent in ion-releasing MOFs/nanofiber composites is emphasized. We further examine the structural hurdles of fabrication, specifically the rheological disruptions and interfacial mismatches that occur during electrospinning. Furthermore, the role of Machine Learning is evaluated as a predictive framework whose clinical accuracy is currently limited by the stochastic nature of the biological systems. Additionally, the impact of MOF architectures on nanofiber piezoelectricity is demonstrated, raising questions regarding the sustainability of electroactive effects during framework decomposition. In this way, this review identifies persistent research gaps in material stability and long-term biocompatibility, providing a realistic roadmap for the development of next-generation bioactive wound interfaces.