Guedan-Duran Atocha, Jemni-Damer Nahla, Orueta-Zenarruzabeitia Irune, Guinea Gustavo Víctor, Perez-Rigueiro José, Gonzalez-Nieto Daniel, Panetsos Fivos
Neuro-computing and Neuro-robotics Research Group, Complutense University of Madrid, Madrid, Spain.
Innovation Group, Institute for Health Research San Carlos Clinical Hospital (IdISSC), Madrid, Spain.
Front Bioeng Biotechnol. 2020 Nov 3;8:584823. doi: 10.3389/fbioe.2020.584823. eCollection 2020.
The regenerative capacity of the peripheral nervous system after an injury is limited, and a complete function is not recovered, mainly due to the loss of nerve tissue after the injury that causes a separation between the nerve ends and to the disorganized and intermingled growth of sensory and motor nerve fibers that cause erroneous reinnervations. Even though the development of biomaterials is a very promising field, today no significant results have been achieved. In this work, we study not only the characteristics that should have the support that will allow the growth of nerve fibers, but also the molecular profile necessary for a specific guidance. To do this, we carried out an exhaustive study of the molecular profile present during the regeneration of the sensory and motor fibers separately, as well as of the effect obtained by the administration and inhibition of different factors involved in the regeneration. In addition, we offer a complete design of the ideal characteristics of a biomaterial, which allows the growth of the sensory and motor neurons in a differentiated way, indicating (1) size and characteristics of the material; (2) necessity to act at the microlevel, on small groups of neurons; (3) combination of molecules and specific substrates; and (4) temporal profile of those molecules expression throughout the regeneration process. The importance of the design we offer is that it respects the complexity and characteristics of the regeneration process; it indicates the appropriate temporal conditions of molecular expression, in order to obtain a synergistic effect; it takes into account the importance of considering the process at the group of neuron level; and it gives an answer to the main limitations in the current studies.
外周神经系统损伤后的再生能力有限,无法完全恢复功能,主要原因是损伤后神经组织的丧失导致神经末梢分离,以及感觉和运动神经纤维杂乱交织的生长导致错误的再支配。尽管生物材料的开发是一个非常有前景的领域,但目前尚未取得显著成果。在这项工作中,我们不仅研究了支持神经纤维生长所需的特性,还研究了特定引导所需的分子特征。为此,我们分别对外周感觉和运动神经纤维再生过程中存在的分子特征,以及不同再生相关因子的施用和抑制所产生的效果进行了详尽研究。此外,我们还提供了一种生物材料理想特性的完整设计方案,该方案能使感觉和运动神经元以分化的方式生长,具体包括:(1)材料的尺寸和特性;(2)在微观层面作用于小群神经元的必要性;(3)分子与特定底物的组合;(4)这些分子在整个再生过程中的表达时间分布。我们提供的设计方案的重要性在于,它尊重再生过程的复杂性和特征;指明了分子表达的合适时间条件,以获得协同效应;考虑到了在神经元群体水平上研究该过程的重要性;并且解决了当前研究中的主要局限性。