Multilevel neurium-mimetic individualized graft via additive manufacturing for efficient tissue repair

Lingchi Kong, Xin Gao, Xiangyun Yao, Haijiao Xie, Qinglin Kang, Wei Sun (), Zhengwei You (), Yun Qian () and Cunyi Fan ()
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Lingchi Kong: Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
Xin Gao: Research Base of Textile Materials for Flexible Electronics and Biomedical Applications (China Textile Engineering Society), Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine
Xiangyun Yao: Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
Haijiao Xie: Hangzhou Yanqu Information Technology Co.Ltd.
Qinglin Kang: Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
Wei Sun: Research Base of Textile Materials for Flexible Electronics and Biomedical Applications (China Textile Engineering Society), Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine
Zhengwei You: Research Base of Textile Materials for Flexible Electronics and Biomedical Applications (China Textile Engineering Society), Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine
Yun Qian: Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
Cunyi Fan: Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine

Nature Communications, 2024, vol. 15, issue 1, 1-17

Abstract: Abstract Complicated peripheral nerve injuries or defects, especially at branching sites, remain a prominent clinical challenge after the application of different treatment strategies. Current nerve grafts fail to match the expected shape and size for delicate and precise branched nerve repair on a case-by-case basis, and there is a lack of geometrical and microscale regenerative navigation. In this study, we develop a sugar painting-inspired individualized multilevel epi-/peri-/endoneurium-mimetic device (SpinMed) to customize natural cues, featuring a selectively protective outer sheath and an instructive core, to support rapid vascular reconstruction and consequent efficient neurite extension along the defect area. The biomimetic perineurium dictates host-guest crosslinking in which new vessels secrete multimerin 1 binding to the fibroin filler surface as an anchor, contributing to the biological endoneurium that promotes Schwann cell homing and remyelination. SpinMed implantation into rat sciatic nerve defects yields a satisfactory outcome in terms of structural reconstruction, with sensory and locomotive function restoration. We further customize SpinMed grafts based on anatomy and digital imaging, achieving rapid repair of the nerve trunk and branches superior to that achieved by autografts and decellularized grafts in a specific beagle nerve defect model, with reliable biosafety. Overall, this intelligent art-inspired biomimetic design offers a facile way to customize sophisticated high-performance nerve grafts and holds great potential for application in translational regenerative medicine.

Date: 2024
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DOI: 10.1038/s41467-024-49980-w

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