Ngo Teri-T B, Waggoner Paula J, Romero Andres A, Nelson Kevin D, Eberhart Robert C, Smith George M
Department of Physiology, Spinal Cord and Brain Injury Research Center, University of Kentucky, Albert B. Chandler Medical Center, Lexington 40536-0298, USA.
J Neurosci Res. 2003 Apr 15;72(2):227-38. doi: 10.1002/jnr.10570.
After injury, axonal regeneration occurs across short gaps in the peripheral nervous system, but regeneration across larger gaps remains a challenge. To improve regeneration across extended nerve defects, we have fabricated novel microfilaments with the capability for drug release to support cellular migration and guide axonal growth across a lesion. In this study, we examine the nerve repair parameters of non-loaded filaments. To examine the influence of packing density on nerve repair, wet-spun poly(L-Lactide) (PLLA) microfilaments were bundled at densities of 3.75, 7.5, 15, and 30% to bridge a 1.0-cm gap lesion in the rat sciatic nerve. After 10 weeks, nerve cable formation increased significantly in the filament bundled groups when compared to empty-tube controls. At lower packing densities, the number of myelinated axons was more than twice that of controls or the highest packing density. In a consecutive experiment, PLLA bundles with lower filament-packing density were examined for nerve repair across 1.4- and 1.8-cm gaps. After 10 weeks, the number of successful regenerated nerves receiving filaments was more than twice that of controls. In addition, nerve cable areas for control groups were significantly less than those observed for filament groups. Axonal growth across 1.4- and 1.8-cm gaps was more consistent for the filament groups than for controls. These initial results demonstrate that PLLA microfilaments enhance nerve repair and regeneration across large nerve defects, even in the absence of drug release. Ongoing studies are examining nerve regeneration using microfilaments designed to release neurotrophins or cyclic AMP.
损伤后，轴突在周围神经系统的短间隙中能够再生，但跨越较大间隙的再生仍然是一个挑战。为了改善在更长神经缺损处的再生，我们制备了具有药物释放能力的新型微丝，以支持细胞迁移并引导轴突跨越损伤部位生长。在本研究中，我们检测了未负载微丝的神经修复参数。为了研究堆积密度对神经修复的影响，将湿纺聚（L-丙交酯）（PLLA）微丝以3.75%、7.5%、15%和30%的密度进行束状排列，以桥接大鼠坐骨神经1.0厘米的间隙损伤。10周后，与空管对照组相比，微丝束状排列组的神经束形成显著增加。在较低堆积密度下，有髓轴突的数量是对照组或最高堆积密度组的两倍多。在连续实验中，检测了较低微丝堆积密度的PLLA束在1.4厘米和1.8厘米间隙处的神经修复情况。10周后，接受微丝的成功再生神经数量是对照组的两倍多。此外，对照组的神经束面积明显小于微丝组。微丝组在1.4厘米和1.8厘米间隙处的轴突生长比对照组更一致。这些初步结果表明，即使在没有药物释放的情况下，PLLA微丝也能增强在大神经缺损处的神经修复和再生。正在进行的研究正在检测使用设计用于释放神经营养因子或环磷酸腺苷的微丝进行神经再生的情况。
