Harley B A, Spilker M H, Wu J W, Asano K, Hsu H-P, Spector M, Yannas I V
Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, Mass., USA.
Cells Tissues Organs. 2004;176(1-3):153-65. doi: 10.1159/000075035.
The experimental study of peripheral nerve regeneration has depended heavily on the use of a nerve chamber in which the stumps of the transected nerve are inserted. A large variety of chamber fillings and chamber types have been used in an effort to induce a higher quality of regeneration across the gap initially separating the two stumps. In this study we studied the morphology of nerves regenerated across a 15 mm gap following implantation of a series of five chambers. The chambers were fabricated from type I collagen and possessed identical pore volume fractions as well as average pore diameters, but differed in cross-link density continuously along the series. The residual mass of the implanted chambers at 9 weeks was observed to increase continuously with increasing cross-link density along the series, indicating a continuous decrease in degradation rate. The quality of regenerated nerves, determined by the number of large diameter fibers (A-fibers) per nerve, the average diameter of all axons and the ratio of area occupied by axons (N-Ratio), was superior at an intermediate level of chamber degradation rate. The maximal quality of peripheral nerve regeneration corresponded to an optimal degradation rate with an estimated chamber half-life of approximately 2-3 weeks following implantation. A speculative mechanistic explanation of the observed optimum focuses on the hypothetical role of cell and cytokine traffic that may take place through holes in the chamber generated by the degradation process. The data show the presence of a hitherto unreported optimal chamber degradation rate that leads to regenerated nerves of maximum quality.
周围神经再生的实验研究在很大程度上依赖于使用神经腔，将横断神经的残端插入其中。为了诱导跨越最初分隔两个残端的间隙实现更高质量的再生，人们使用了各种各样的腔填充物和腔类型。在本研究中，我们研究了植入一系列五个神经腔后，跨越15毫米间隙再生的神经的形态。这些神经腔由I型胶原蛋白制成，具有相同的孔隙体积分数和平均孔径，但沿该系列交联密度连续变化。观察到在9周时，植入神经腔的剩余质量随着该系列交联密度的增加而持续增加，表明降解速率持续降低。由每条神经中大直径纤维（A纤维）的数量、所有轴突的平均直径以及轴突所占面积的比例（N比例）所确定的再生神经质量，在神经腔降解速率的中间水平时更佳。周围神经再生的最大质量对应于最佳降解速率，植入后估计神经腔的半衰期约为2 - 3周。对观察到的最佳情况的一种推测性机理解释聚焦于细胞和细胞因子运输可能通过降解过程在神经腔中产生的孔洞所发挥的假设作用。数据显示存在一种迄今未报道的最佳神经腔降解速率，其能产生质量最高的再生神经。
