Smith Dominique R, Dumont Courtney M, Ciciriello Andrew J, Guo Amina, Tatineni Ravindra, Munsell Mary K, Cummings Brian J, Anderson Aileen J, Shea Lonnie D
Department of Biomedical Engineering, University of Michigan, 2200 Bonisteel Avenue, Ann Arbor, Michigan 48109, United States.
Department of Biomedical Engineering, University of Miami, 1251 Memorial Drive, Coral Gables, Florida 33156, United States.
ACS Biomater Sci Eng. 2019 Dec 9;5(12):6679-6690. doi: 10.1021/acsbiomaterials.9b01012. Epub 2019 Nov 14.
Spinal cord injury (SCI) is a devastating condition that may cause permanent functional loss below the level of injury, including paralysis and loss of bladder, bowel, and sexual function. Patients are rarely treated immediately, and this delay is associated with tissue loss and scar formation that can make regeneration at chronic time points more challenging. Herein, we investigated regeneration using a poly(lactide--glycolide) multichannel bridge implanted into a chronic SCI following surgical resection of necrotic tissue. We characterized the dynamic injury response and noted that scar formation decreased at 4 and 8 weeks postinjury (wpi), yet macrophage infiltration increased between 4 and 8 wpi. Subsequently, the scar tissue was resected and bridges were implanted at 4 and 8 wpi. We observed robust axon growth into the bridge and remyelination at 6 months after initial injury. Axon densities were increased for 8 week bridge implantation relative to 4 week bridge implantation, whereas greater myelination, particularly by Schwann cells, was observed with 4 week bridge implantation. The process of bridge implantation did not significantly decrease the postinjury function. Collectively, this chronic model follows the pathophysiology of human SCI, and bridge implantation allows for clear demarcation of the regenerated tissue. These data demonstrate that bridge implantation into chronic SCI supports regeneration and provides a platform to investigate strategies to buttress and expand regeneration of neural tissue at chronic time points.
脊髓损伤（SCI）是一种严重的病症，可能导致损伤平面以下的永久性功能丧失，包括瘫痪以及膀胱、肠道和性功能丧失。患者很少能得到立即治疗，而这种延迟与组织损失和瘢痕形成有关，这会使在慢性时间点的再生更具挑战性。在此，我们使用聚（丙交酯-乙交酯）多通道桥接物进行再生研究，该桥接物在坏死组织手术切除后植入慢性脊髓损伤部位。我们对动态损伤反应进行了表征，注意到损伤后4周和8周（wpi）瘢痕形成减少，但巨噬细胞浸润在4至8 wpi之间增加。随后，在4 wpi和8 wpi时切除瘢痕组织并植入桥接物。我们观察到在初次损伤后6个月有大量轴突生长进入桥接物并进行了髓鞘再生。相对于4周桥接物植入，8周桥接物植入后的轴突密度增加，而4周桥接物植入时观察到更多的髓鞘形成，尤其是施万细胞形成的髓鞘。桥接物植入过程并未显著降低损伤后的功能。总体而言，这种慢性模型遵循人类脊髓损伤的病理生理学，并且桥接物植入允许对再生组织进行清晰的界定。这些数据表明，将桥接物植入慢性脊髓损伤可支持再生，并提供了一个平台来研究在慢性时间点支持和扩大神经组织再生的策略。
