Immune-Responsive Bioinks Enable Vision-Guided In situ Robotic Bioprinting to Accelerate Diabetic Wound Healing

Chronic diabetic wounds remain a major clinical challenge because persistent inflammation, hypoxia, and immune dysregulation prevent the transition of macrophages from pro-inflammatory M1 states to pro-regenerative M2 phenotypes. Here, we report an immunomodulatory colloidal bioink that integrates zein-based oxygen-generating microparticles and human mesenchymal stem cells within a porous, mechanically robust matrix for adaptive in situ bioprinting. Implemented with the autonomous, intelligent, visually guided in situ robotic bioprinting platform, this bioink enables patient-specific deposition directly onto wound defects with high spatial conformity and stable tissue integration. Sustained oxygen release alleviates local hypoxic stress, enhances stem cell survival, and reshapes the wound microenvironment to favor regenerative immune responses. In diabetic wound models, the printed constructs promote angiogenesis, accelerate wound closure, and improve tissue regeneration. Spatial transcriptomic analysis further reveals macrophage heterogeneity across wound compartments and identifies a coordinated M1-to-M2 transition spatially and transcriptionally associated with the combined contribution of oxygen modulation and stem cell-derived paracrine signaling. Together, this study establishes a therapeutic strategy that combines intelligent biomaterial design, controlled hypoxic conditioning, and adaptive robotic bioprinting to achieve precision immunomodulation and personalized regenerative treatment for chronic diabetic wounds with clinical translational potential and broad future applicability.