Silk-Based Wound Healing Materials from Molecular Bioactivity to Smart and Responsive Dressings

Chronic and complex wounds impose a heavy clinical and economic burden, and the materials used to manage them are moving from passive coverings towards dressings that interact biologically with the wound bed or respond to its changing microenvironment. Silk proteins, principally fibroin and sericin from the domesticated silkworm Bombyx mori together with non-mulberry and recombinant spider silk variants, have become prominent candidates because they combine tunable mechanics, aqueous processability, controllable degradation and reported pro-healing activity. This critical narrative review examines how far the evidence supports the progression of silk-based wound materials from molecular bioactivity to stimulus-responsive and sensing dressings. Peer-reviewed literature published from January 2000 to August 2026 was identified through structured searches of biomedical and multidisciplinary scholarly indexes, supplemented by citation tracking, and was appraised qualitatively for design adequacy, model validity, material characterisation and translational relevance. The synthesis indicates that fibroin and sericin can engage keratinocyte and fibroblast signalling, macrophage responses and angiogenic pathways in vitro and in rodent models, but these effects are strongly conditioned by degumming, molecular weight, secondary structure and residual sericin, so intrinsic bioactivity is seldom separable from processing history, scaffold architecture or loaded therapeutics. Preclinical efficacy is consistent yet rests mainly on small, short-term rodent studies with heterogeneous comparators and limited use of contraction-controlled or porcine models. Clinical evidence comprises a small number of randomised and pilot trials, largely in acute surgical wounds and skin graft donor sites, with no adequately powered trial in diabetic, venous or pressure ulcers. Responsive silk dressings that release drugs in response to pH, proteases, glucose or light, or that report temperature, pH or bacterial signatures, remain predominantly open-loop proofs of concept, and the specific contribution of silk relative to inorganic or synthetic components is rarely tested. Priority needs include standardised reporting of silk material attributes, mechanism studies using defined and endotoxin-controlled preparations, validation of sensing performance in real exudate, and pragmatic trials in chronic wound populations. Silk is a credible platform for advanced wound care, but its translational promise exceeds the current strength of evidence.