Yannas Ioannis V, Zhang Mei, Spilker Mark H
Department of Mechanical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
J Biomater Sci Polym Ed. 2007;18(8):943-66. doi: 10.1163/156856207781494386.
Progress in understanding conditions for optimal peripheral nerve regeneration has been stunted due to lack of standardization of experimental conditions and assays. In this paper we review the large database that has been generated using the Lundborg nerve chamber model and compare various theories for their ability to explain the experimental data. Data were normalized based on systematic use of the critical axon elongation, the gap length at which the probability of axon reconnection between the stumps is just 50%. Use of this criterion has led to a rank-ordering of devices or treatments and has led, in turn, to conclusions about the conditions that facilitate regeneration. Experimental configurations that have maximized facilitation of peripheral nerve regeneration are those in which the tube wall comprised degradable polymers, including collagen and certain synthetic biodegradable polymers, and was cell-permeable rather than protein-permeable. Tube fillings that showed very high regenerative activity were suspensions of Schwann cells, a solution either of acidic or basic fibroblast growth factor, insoluble ECM substrates rather than solutions or gels, polyamide filaments oriented along the tube axis and highly porous, insoluble analogs of the ECM with specific structure and controlled degradation rate. It is suggested that the data are best explained by postulating that the quality of regeneration depends on two critical processes. The first is compression of stumps and regenerating nerve by a thick myofibroblast layer that surrounds these tissues and blocks synthesis of a nerve of large diameter (pressure cuff theory). The second is synthesis of linear columns of Schwann cells that serve as tracks for axon elongation (basement membrane microtube theory). It is concluded that experimental configurations that show high regenerative activity suppress the first process while facilitating the second.
由于实验条件和检测方法缺乏标准化，在理解最佳外周神经再生条件方面的进展一直受到阻碍。在本文中，我们回顾了使用伦德伯格神经腔模型生成的大型数据库，并比较了各种理论解释实验数据的能力。数据基于对关键轴突伸长的系统使用进行了归一化，即残端之间轴突重新连接概率恰好为50%时的间隙长度。使用该标准导致了装置或治疗方法的排序，并进而得出了关于促进再生条件的结论。在外周神经再生促进效果最大化的实验配置中，管壁由可降解聚合物组成，包括胶原蛋白和某些合成可生物降解聚合物，并且是细胞可渗透而非蛋白质可渗透的。显示出非常高再生活性的管填充物是施万细胞悬液、酸性或碱性成纤维细胞生长因子溶液、不溶性细胞外基质底物而非溶液或凝胶、沿管轴定向且高度多孔的聚酰胺细丝、具有特定结构和可控降解速率的不溶性细胞外基质类似物。有人提出，通过假设再生质量取决于两个关键过程，可以最好地解释这些数据。第一个过程是围绕这些组织的厚肌成纤维细胞层对残端和再生神经的压缩，这会阻碍大直径神经的合成（压力袖带理论）。第二个过程是施万细胞线性柱的合成，其作为轴突伸长的轨迹（基底膜微管理论）。得出的结论是，显示出高再生活性的实验配置抑制了第一个过程，同时促进了第二个过程。
