Patient-as-bioreactor in-body tissue architecture generates autologous multicellular constructs for durable diabetic wound repair

Chronic diabetic foot ulcers remain refractory to contemporary care, partly because durable repair requires reconstruction of an integrated, multicellular regenerative niche—an outcome rarely achieved without complex ex vivo manufacturing. We advance a patient-as-bioreactor paradigm in which in-body tissue architecture (iBTA) repurposes the body for in vivo manufacturing of autologous multicellular regenerative constructs (“biococktails”) using a temporary subcutaneous device. In a first-in-human exploratory study, 37 devices were successfully implanted, and the primary endpoint—generation of ≥ 1 construct meeting predefined quality criteria—was achieved in all 10 patients. A single application initiated sustained wound repair, reaching a mean 84.15% wound-area reduction at 12 weeks. Reproducible, self-assembled niches enriched for stem cell–associated programs, reparative macrophage signatures, nascent vasculature, extracellular matrix components, and broad regenerative signaling were observed. No amputations or treatment-related serious adverse events occurred. These findings establish iBTA as a scalable, patient-specific in vivo manufacturing platform for multicellular regenerative therapies.