Restoring nervous system structure and function using tissue engineered living scaffolds  

作　　者：Laura A.Struzyna James P.Harris Kritika S.Katiyar H.Isaac Chen D.Kacy Cullen 

机构地区：[1]Center for Brain Injury and Repair,Department of Neurosurgery,Perelman School of Medicine,University of Pennsylvania [2]Center for Neurotrauma,Neurodegeneration,and Restoration,Philadelphia Veterans Affairs Medical Center [3]School of Biomedical Engineering,Drexel University

出　　处：《Neural Regeneration Research》2015年第5期679-685,共7页中国神经再生研究（英文版）

基　　金：support provided by the U.S.Army Medical Research and Materiel Command through the Joint Warfighter Medical Research Program(#W81XWH-13-13207004);Axonia Medical,Inc.;Department of Veterans Affairs(RR&D Merit Review#B1097-I);National Institutes of Health(NINDS T32-NS043126);Penn Medicine Neuroscience Center;the National Science Foundation(Graduate Research Fellowship DGE-1321851)

摘　　要：Neural tissue engineering is premised on the integration of engineered living tissue with the host nervous system to directly restore lost function or to augment regenerative capacity following ner- vous system injury or neurodegenerative disease. Disconnection of axon pathways - the long-distance fibers connecting specialized regions of the central nervous system or relaying peripheral signals - is a common feature of many neurological disorders and injury. However, functional axonal regenera- tion rarely occurs due to extreme distances to targets, absence of directed guidance, and the presence of inhibitory factors in the central nervous system, resulting in devastating effects on cognitive and sensorimotor function. To address this need, we are pursuing multiple strategies using tissue engi- neered ＂living scaffolds＂, which are preformed three-dimensional constructs consisting of living neural cells in a defined, often anisotropic architecture. Living scaffolds are designed to restore function by serving as a living labeled pathway for targeted axonal regeneration - mimicking key developmental mechanisms- or by restoring lost neural circuitry via direct replacement of neurons and axonal tracts. We are currently utilizing preformed living scaffolds consisting of neuronal dusters spanned by long axonal tracts as regenerative bridges to facilitate long-distance axonal regeneration and for targeted neurosurgical reconstruction of local circuits in the brain. Although there are formidable challenges in predinical and clinical advancement, these living tissue engineered constructs represent a promising strategy to facilitate nervous system repair and functional recovery.Neural tissue engineering is premised on the integration of engineered living tissue with the host nervous system to directly restore lost function or to augment regenerative capacity following ner- vous system injury or neurodegenerative disease. Disconnection of axon pathways - the long-distance fibers connecting specialized regions of the central nervous system or relaying peripheral signals - is a common feature of many neurological disorders and injury. However, functional axonal regenera- tion rarely occurs due to extreme distances to targets, absence of directed guidance, and the presence of inhibitory factors in the central nervous system, resulting in devastating effects on cognitive and sensorimotor function. To address this need, we are pursuing multiple strategies using tissue engi- neered ＂living scaffolds＂, which are preformed three-dimensional constructs consisting of living neural cells in a defined, often anisotropic architecture. Living scaffolds are designed to restore function by serving as a living labeled pathway for targeted axonal regeneration - mimicking key developmental mechanisms- or by restoring lost neural circuitry via direct replacement of neurons and axonal tracts. We are currently utilizing preformed living scaffolds consisting of neuronal dusters spanned by long axonal tracts as regenerative bridges to facilitate long-distance axonal regeneration and for targeted neurosurgical reconstruction of local circuits in the brain. Although there are formidable challenges in predinical and clinical advancement, these living tissue engineered constructs represent a promising strategy to facilitate nervous system repair and functional recovery.

关 键 词：living scaffolds neural tissue engineering cell transplant BIOMATERIALS regeneration NEUROTRAUMA NEURODEGENERATION axon pathfinding cell migration 

分 类 号：R318.08[医药卫生—生物医学工程]