Hierarchical Integration of MOF-Based Nanoplatforms with Electrospun Nanofiber Scaffolds for Spatiotemporally Sustained Diabetic Wound Healing.

Abstract

Currently, diabetic wound dressings continue to exhibit various limitations, hindering their ability to effectively respond to the dynamic and complex microenvironment of diabetic wounds. Particularly, significant challenges remain in developing multifunctional dressings capable of effective multicomponent integration and precise, controlled release of each component. Herein, the novel electrospun nanofiber composite membranes (NCMs) are developed that hierarchically incorporate zeolitic imidazolate framework (ZIF)-based nanoplatforms for spatiotemporally controlled and continuous release of multiple bioactive components, enabling the effective regulation of key factors involved in diabetic wound healing. Specifically, platelet-derived growth factor-BB (PDGF-BB)-loaded ZIF-8 (PZ) nanoparticles (NPs) are embedded within poly(ε-caprolactone)/gelatin (PCL/GT) nanofibers, while ZIF-67 NPs are in situ grown on the nanofiber surface, yielding multifunctional ZIF-67/PZ/PCL/GT (ZPZPG) NCMs. The hierarchical structures facilitate a staged pH-responsive release, wherein initially released Co²⁺ from ZIF-67 NPs rapidly exerts antibacterial effects and promotes early angiogenesis, followed by the prolonged release of Zn²⁺ and PDGF-BB from embedded ZIF-8 NPs, further enhancing antimicrobial activity, neovascularization, fibroblast proliferation, and tissue regeneration. Both in vitro and in vivo studies demonstrate effective infection control, improved vascularization, and accelerated wound healing, underscoring the potential of hierarchical metal-organic framework (MOF)-integrated NCMs as an attractive way to overcome current limitations in diabetic wound therapy.