Designing metal-organic framework-growth factor interfaces for stage-matched chronic wound repair: from molecular binding to composite architectures

Chronic wounds are sustained by coupled failures in inflammation control, infection resolution, redox homeostasis, protease regulation, and angiogenesis, which destabilize growth factors (GFs) and disrupt the temporal sequence of repair. Metal-organic frameworks (MOFs) offer a designable route to address this problem because metal-node chemistry, linker composition, pore and defect structure, particle architecture, and composite processing can be coordinated within one platform. This Review develops a structure-interface-function framework for MOF-enabled GF regulation in chronic wound repair. We examine how surface adsorption, biomineralization-derived framework encapsulation, and confinement within accessible hierarchical pore domains control GF loading, conformational protection, release, and post-release activity; how responsive framework transformation and bioactive ion exposure couple microenvironment remodeling with endogenous or exogenous GF signaling; and how hydrogels, nanofibers, microneedles, and multilayer scaffolds translate nanoscale interactions into spatially and temporally organized therapy. Direct GF delivery is distinguished from indirect signaling regulation, and current evidence is evaluated against requirements for interface-resolved characterization, coupled release modeling, reproducible processing, wound-relevant exposure assessment, and long-term safety. These design principles position MOFs as programmable regenerative interfaces rather than passive protein reservoirs.