Abstract
The central nervous system (CNS) has very restricted intrinsic regeneration ability under the injury or disease condition. Innovative repair strategies, therefore, are urgently needed to facilitate tissue regeneration and functional recovery. The published tissue repair/regeneration strategies, such as cell and/or drug delivery, has been demonstrated to have some therapeutic effects on experimental animal models, but can hardly find clinical applications due to such methods as the extremely low survival rate of transplanted cells, difficulty in integrating with the host or restriction of blood–brain barriers to administration patterns. Using biomaterials can not only increase the survival rate of grafts and their integration with the host in the injured CNS area, but also sustainably deliver bioproducts to the local injured area, thus improving the microenvironment in that area. This review mainly introduces the advances of various strategies concerning facilitating CNS regeneration.
Highlights
The central nervous system (CNS) diseases, such as Parkinson’s disease, Alzheimer’s disease [1, 2] and traumas, are all caused by neuronal loss or injury, which lead to the sensory, locomotion and cognitive dysfunction because of the absence of the axonal growth stimulative factors, like local growth stimulative substances and extracellular matrix (ECM) protein, and the existence of axonal growth inhibitory factors, like myelin-associated proteins and the physical/chemical barriers formed by glial scars [3]
Taking the spinal cord or brain injury of adult rats as the experimental models, our research team has long been devoted to using chitosan biomaterial scaffolds to repair CNS injury, and evidenced that the neurotrophic factor-3 (NT-3) chitosan scaffold enables the neural regeneration of the brain and spinal cord [20, 36, 83, 84], based on which we have further revealed that the NT-3 chitosan scaffold can activate endogenous neurogenesis and realize the functional recovery after rat spinal cord injury (SCI) [16], as well as explored its underlying molecular mechanism via transcriptome analysis [85]
A better understanding of the cellular and molecular control mechanism of NSCs/NPCs differentiation during the developmental stage and in the adult CNS is of great significance to activating endogenous neurogenesis and reconstructing the functional neural circuit lost because of injuries or diseases
Summary
The central nervous system (CNS) diseases, such as Parkinson’s disease, Alzheimer’s disease [1, 2] and traumas, are all caused by neuronal loss or injury, which lead to the sensory, locomotion and cognitive dysfunction because of the absence of the axonal growth stimulative factors, like local growth stimulative substances and extracellular matrix (ECM) protein, and the existence of axonal growth inhibitory factors, like myelin-associated proteins and the physical/chemical barriers formed by glial scars [3]. It has been widely accepted that there are neural stem/precursor cells (NSCs/ NPCs) which can generate new neurons in multiple areas of the adult mammalian CNS, such as the olfactory bulb, hippocampus dentate gyrus, periventricular area and central canal of the spinal cord [4,5,6,7,8,9]. This article focuses on the strategies about facilitating CNS regeneration, including cell transplantation and endogenous neurogenesis, especially using biomaterials to facilitate tissue regeneration and functional recovery after brain and spinal cord injury (SCI). Exogenous cells are transplanted after the CNS injury to substitute dead or injured tissues. The direct drug delivery or transplantation bypassing the BBB, e.g., direct injection into the injured local site or intracerebroventricular (ICV) injection, may be taken into consideration, but probably accompanied by such risks as cerebral edema and convulsion, where drugs will diffuse quickly and get removed, with slight or no biological effects at all [21]
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