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肿胀诱导硬化和降解诱导缓慢膨胀水凝胶用于改良的脊髓压迫动物模型。

Swelling Induced Hardening and Degradation Induced Slow-Expansion Hydrogel for a Modified Cervical Spinal Cord Compression Animal Model.

机构信息

Peking University Third Hospital, Department of Orthopaedics, Beijing 100191, China.

Engineering Research Center of Bone and Joint Precision Medicine, Beijing 100191, China.

出版信息

ACS Appl Mater Interfaces. 2024 Oct 30;16(43):58274-58285. doi: 10.1021/acsami.4c12023. Epub 2024 Oct 22.

Abstract

This study presents the development of a polyurethane hydrogel (PUG) for use in a chronic cervical spinal cord compression animal model, leveraging microphase separation and dynamic covalent bonds to achieve swelling induced hardening and degradation-induced slow expansion. PUG-SS and PUG-SS-60% were synthesized with varying disulfide bond concentrations, offering controllable degradation rates and mechanical properties. The hydrogels demonstrated significant swelling-induced hardening and maintained compression above the cervical spinal cord's intrinsic modulus. MRI and histopathological analyses confirmed effective and sustained spinal cord compression, with PUG-SS-60% showing prolonged effects. Behavioral tests, including the BBB locomotor scale, von Frey pain test, and catwalk gait analysis, indicated quicker motor function recovery with PUG-SS and sustained compression with PUG-SS-60%. In vitro cytotoxicity assays showed no significant hydrogel-induced cell death. This study underscores the potential of PUG-SS-60% for providing controlled, sustained compression in chronic spinal cord compression models, paving the way for advanced nonsurgical treatment strategies and improved understanding of degenerative cervical myelopathy (DCM) pathology.

摘要

本研究开发了一种用于慢性颈脊髓压迫动物模型的聚氨酯水凝胶(PUG),利用微相分离和动态共价键实现了溶胀诱导的硬化和降解诱导的缓慢膨胀。通过改变二硫键浓度合成了 PUG-SS 和 PUG-SS-60%,提供了可控的降解率和力学性能。水凝胶表现出显著的溶胀诱导硬化,并保持在颈脊髓固有模量以上的压缩。MRI 和组织病理学分析证实了有效的和持续的脊髓压迫,PUG-SS-60% 显示出延长的效果。行为学测试,包括 BBB 运动评分、von Frey 疼痛测试和猫步步态分析,表明 PUG-SS 具有更快的运动功能恢复和 PUG-SS-60% 的持续压缩。体外细胞毒性试验表明水凝胶没有引起明显的细胞死亡。本研究强调了 PUG-SS-60% 在慢性脊髓压迫模型中提供可控、持续压缩的潜力,为先进的非手术治疗策略和对退行性颈髓病(DCM)病理的深入理解铺平了道路。

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