Living bio interfaces for chronic wounds: Next generation scaffolds for the spatiotemporal delivery of Lactiplantibacillus plantarum

Diabetic foot ulcers present a critical clinical challenge, with five-year mortality exceeding 50%, comparable to several aggressive malignancies. Their persistence reflects a pathophysiological gridlock: a self-amplifying circuit of advanced glycation end-products, reactive oxygen species and NOD-like receptor protein 3 (NLRP3) inflammasome activation. This review examines Lactiplantibacillus plantarum as a living medicine capable of reorchestrating that microenvironment. Emerging evidence indicates that L. plantarum and its metabolites may inhibit NLRP3-mediated pyroptosis and promote proreparative M2 macrophage polarization, addressing causes of impaired healing rather than symptoms. Topical efficacy is nonetheless constrained by the hostile, oxidative ulcer environment. Delivery platforms are assessed — injectable living hydrogels, cryolyophilized sponges, electrospun fibers, microcapsules and microneedles — designed to preserve viability and control metabolite release. Representative data show both the promise and the present limits: injectable living hydrogels retain over 80% of entrapped L. plantarum and achieve a 7-log reduction of P. aeruginosa on human skin wound models, whereas electrospun formats reach 7.6 × 10⁸ colony-forming units mg⁻¹ with 24-week stability but release their cargo within 30 min. Synergistic strategies combining nanozymes and prebiotics target multidrug-resistant biofilms and oxidative stress, the recurring difficulty being that agents which help the wound often harm the probiotic. A translational roadmap addresses the sterilization paradox and the regulatory landscape for live biotherapeutic products. Three obstacles remain decisive: sterilization, the absence of comparable viability reporting across platforms, and the absence of any health-economic evaluation.