An integrated long-acting implant of clinical safe cells, drug and biomaterials effectively promotes spinal cord repair and restores motor functions,Journal of Controlled Release

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An integrated long-acting implant of clinical safe cells, drug and biomaterials effectively promotes spinal cord repair and restores motor functions
Journal of Controlled Release ( IF 10.5 ) Pub Date : 2024-09-12 , DOI: 10.1016/j.jconrel.2024.09.010
Liming Li ₁ , Jiafu Mu ₂ , Jiachen Chen ₂ , Tianchen Huang ₂ , Yu Zhang ₂ , Youzhi Cai ₃ , Tianyuan Zhang ₂ , Xianglei Kong ₄ , Jihong Sun ₄ , Xinchi Jiang ₂ , Jiahe Wu ₂ , Jian Cao ₂ , Xunqi Zhang ₂ , Fei Huang ₅ , Shiqing Feng ₆ , Jianqing Gao ₇

Affiliation

Spinal cord injury (SCI) is incurable and raises growing concerns. The main barrier to nerve repair is the complicated inhibitory microenvironment, where single-targeted strategies are largely frustrated. Despite the progress in combinatory therapeutic systems, the development and translation of effective therapies remain a challenge with extremely limited clinical materials. In this study, mesenchymal stem cells are transplanted in combination with sustained release of methylprednisolone through delivery in one composite matrix of a microsphere-enveloped adhesive hydrogel. All the materials used, including the stem cells, drug, and the matrix polymers gelatin and hyaluronan, are clinically approved. The therapeutic effects and safety issues are evaluated on rat and canine SCI models. The implantation significantly promotes functional restoration and nerve repair in a severe long-span rat spinal cord transection model. Distant spinal cord segments and the urinary system are effectively protected against pathologic damage. Moreover, the local sustained drug delivery mitigates the inflammatory microenvironment when overcoming the clinical issue of systemic side effects. The study presents an innovative strategy to achieve safe and efficient combinatory treatment of SCI.

中文翻译：

临床安全细胞、药物和生物材料的综合长效植入物，有效促进脊髓修复和恢复运动功能

脊髓损伤（SCI）是无法治愈的，引起了越来越多的担忧。神经修复的主要障碍是复杂的抑制性微环境，其中单一靶点策略在很大程度上受挫。尽管组合治疗系统取得了进展，但由于临床材料极其有限，有效疗法的开发和转化仍然是一个挑战。在这项研究中，间充质干细胞与甲基泼尼松龙的持续释放相结合，通过在微球包膜粘合水凝胶的一个复合基质中递送。使用的所有材料，包括干细胞、药物以及基质聚合物明胶和透明质酸，都经过临床批准。在大鼠和犬 SCI 模型上评估治疗效果和安全性问题。植入显着促进了严重大跨度大鼠脊髓横断模型中的功能恢复和神经修复。远处脊髓节段和泌尿系统得到有效保护，免受病理损伤。此外，在克服全身副作用的临床问题时，局部持续药物递送减轻了炎症微环境。该研究提出了一种创新策略，以实现安全有效的 SCI 联合治疗。

更新日期：2024-09-12

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