PDF(Pubmed)
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.
摘要：
复杂的周围神经损伤或缺陷，尤其是在分支部位，在应用不同的治疗策略后，仍然是一个突出的临床挑战。当前的神经移植物无法与预期的形状和大小相匹配，可以根据具体情况进行精细而精确的分支神经修复，缺乏几何和微尺度的再生导航。在这项研究中,我们开发了一种糖绘画启发的个性化多层次的表面/周围/神经内膜模拟装置（SpinMed）来定制自然线索，具有选择性保护性外鞘和有指导性的核心，以支持快速的血管重建和随之而来的有效的神经突延伸沿缺损区域。仿生会阴膜决定了主客体交联，其中新血管分泌多聚蛋白1结合到丝心蛋白填料表面作为锚，有助于促进雪旺氏细胞归巢和髓鞘再生的生物神经内膜。SpinMed植入大鼠坐骨神经缺损在结构重建方面产生了令人满意的结果，具有感官和机车功能恢复。我们根据解剖学和数字成像进一步定制SpinMed移植物，在特定的比格神经缺损模型中，神经干和分支的快速修复优于自体移植物和去细胞移植物，可靠的生物安全。总的来说,这种以艺术为灵感的智能仿生设计提供了一种方便的方式来定制复杂的高性能神经移植物，并在转化再生医学中具有巨大的应用潜力。
