Immune‐Responsive Bioinks Enable Vision‐Guided in Situ Robotic Bioprinting to Accelerate Diabetic Wound Healing

ABSTRACT 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.

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Publication Details

Journal
Advanced Functional Materials
Published
2026-07-23
DOI
https://doi.org/10.1002/adfm.77191
Primary Topic
3D Printing in Biomedical Research
Type
article
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article

Immune‐Responsive Bioinks Enable Vision‐Guided in Situ Robotic Bioprinting to Accelerate Diabetic Wound Healing

Nebras Sobahi, Ki‐Tae Kim, Danilo M. dos Santos, Jae Seo Lee et al.
Advanced Functional Materials
3D Printing in Biomedical Research
article

Immune‐Responsive Bioinks Enable Vision‐Guided in Situ Robotic Bioprinting to Accelerate Diabetic Wound Healing

Nebras Sobahi, Ki‐Tae Kim, Danilo M. dos Santos, Jae Seo Lee, Su Ryon Shin, Eleftheria‐Angeliki Valsami, Georgios Theocharidis, Lance Fiondella, Mohammad Asif Hussain, Woo-Jin Kim, Kyungsang Kim, Brendan Craig Thibault, Aristidis Veves, Seol‐Ha Jeong, Jungmok Seo, Zhuqing Li, Yejin Jo, Mei Li L. Cham‐Pérez, Jarno Hiemstra, Kijun Park, Kim Sk, R S Rodriguez, Javier Alejandro Lozano Soto, Montserrat Legorreta Gonzalez, Jihyun Kim
article en

Abstract

ABSTRACT 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.

Advanced Functional Materials
University of Massachusetts Dartmouth (US), Brigham and Women's Hospital (US), Beth Israel Deaconess Medical Center (US), Seoul National University (KR), King Abdulaziz University (SA), Yonsei University (KR), Massachusetts General Hospital (US), Institute of Molecular Biology (AM), Seoul National University Dental Hospital (KR)
Good health and well-being
Openalex Percentile: Top 15%
3D Printing in Biomedical Research
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