Yi Jiling, Jiang Nan, Li Binbin, Yan Qiongjiao, Qiu Tong, Swaminatha Iyer Killugudi, Yin Yixia, Dai Honglian, Yetisen Ali K, Li Shipu
State Key Laboratory of Advanced Technology for Materials Synthesis and Processing Wuhan University of Technology Wuhan 430070 China.
School of Molecular Sciences University of Western Australia 35 Stirling Hwy Crawley WA 6009 Australia.
Adv Sci (Weinh). 2018 Mar 27;5(6):1700876. doi: 10.1002/advs.201700876. eCollection 2018 Jun.
Neuroma formation after amputation as a long-term deficiency leads to spontaneous neuropathic pain that reduces quality of life of patients. To prevent neuroma formation, capping techniques are implemented as effective treatments. However, an ideal, biocompatible material covering the nerves is an unmet clinical need. In this study, biocompatible characteristics presented by the poly(D,L-lactic acid)/arginylglycylaspartic acid (RGD peptide) modification of poly{(lactic acid)-- [(glycolic acid)-alt-(L-lysine)]} (PRGD/PDLLA) are evaluated as a nerve conduit. After being capped on the rat sciatic nerve stump in vivo, rodent behaviors and tissue structures are compared via autotomy scoring and histological analyses. The PRGD/PDLLA capped group gains lower autotomy score and improves the recovery, where inflammatory infiltrations and excessive collagen deposition are defeated. Transmission electron microscopy images of the regeneration of myelin sheath in both groups show that abnormal myelination is only present in the uncapped rats. Changes in related genes (MPZ, MBP, MAG, and Krox20) are monitored quantitative real-time polymerase chain reaction (qRT-PCR) for mechanism investigation. The PRGD/PDLLA capping conduits not only act as physical barriers to inhibit the invasion of inflammatory infiltration in the scar tissue but also provide a suitable microenvironment for promoting nerve repairing and avoiding neuroma formation during nerve recovery.
截肢后神经瘤形成作为一种长期缺陷会导致自发性神经性疼痛,降低患者的生活质量。为防止神经瘤形成,采用封端技术作为有效治疗方法。然而,覆盖神经的理想生物相容性材料仍是未满足的临床需求。在本研究中,评估了聚(D,L-乳酸)/精氨酰甘氨酰天冬氨酸(RGD肽)修饰的聚{(乳酸)-[(乙醇酸)-交替-(L-赖氨酸)]}(PRGD/PDLLA)作为神经导管所呈现的生物相容性特征。在体内封端大鼠坐骨神经残端后,通过自残评分和组织学分析比较啮齿动物行为和组织结构。PRGD/PDLLA封端组的自残评分较低且恢复情况改善,炎症浸润和过度胶原沉积得到抑制。两组髓鞘再生的透射电子显微镜图像显示,未封端大鼠仅存在异常髓鞘形成。通过定量实时聚合酶链反应(qRT-PCR)监测相关基因(MPZ、MBP、MAG和Krox20)的变化以进行机制研究。PRGD/PDLLA封端导管不仅作为物理屏障抑制瘢痕组织中炎症浸润的侵入,还为促进神经修复和避免神经恢复过程中神经瘤形成提供合适的微环境。