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Spinal cord repair and regeneration
Published in David M. Gardiner, Regenerative Engineering and Developmental Biology, 2017
In mammals, SCI leads to a complex cellular response involving invasion of resident and non-resident immune cells, inflammation, formation of a glial scar, release of inhibitory factors, and alterations in the extracellular matrix, which result in a post-injury environment that is inhospitable for neuronal regrowth, regeneration, and functional recovery (Figure 22.1a–c) (Yiu and He, 2006; Fawcett et al., 2012; Cregg et al., 2014; Silver et al., 2015). Within the first week, resident glial cells in the CNS, including microglia/macrophages and ependymal cells, migrate toward the injury site and begin to proliferate, filling the gap and providing wound-healing functions (Figure 22.1b). However, afterwards, a glial scar forms, in which astrocytes and their processes form an atypically dense network at the lesion periphery (Figure 22.1c) (Yiu and He, 2006; Cregg et al., 2014). Fibroblasts, which deposit extracellular matrix components, and oligodendrocyte precursors, which entrap regrowing axons, together form the lesion core (Cregg et al., 2014). This reactive gliosis thus creates a physical barrier that inhibits subsequent axon regeneration. Adding to the complexity of the problem, the microglia/macrophages that invade after SCI appear to have both pro-regenerative and anti-regenerative roles in the injured CNS (Bloom, 2014; Popovich, 2014; Gensel and Zhang, 2015).
Nanomaterial-Assisted Tissue Engineering and Regenerative Medical therapy
Published in Gilson Khang, Handbook of Intelligent Scaffolds for Tissue Engineering and Regenerative Medicine, 2017
Nirmalya Tripathy, Rafiq Ahmad, Gilson Khang
Xie et al. showed differentiation of RW4 embryonic bodies (EBs) into neuronal lineage cultured on electrospun PCL nanofibers. Tuj1 (for neurons) and O4 markers (for oligodendrocytes) were more expressed on aligned fibers compared to random fibers, while GFAPs (for astrocytes) were less expressed in the aligned case than in the random case. This result suggests that the alignment of nanofibers could promote differentiation into neuronal lineage while suppressing the differentiation into astrocytes. Since the spinal cord injury is frequently not regenerated due to the glial scar formation, these results are potentially useful for suppressing glial cell differentiation while promoting neuronal regeneration.101 Synthetic topography has been utilized for aligned growth of neurons, which is potentially important for neural regeneration.102,103 Clark et al. investigated the behavior of growth cone guidance on various sizes of microscale laminin lines (isolated single 2 μm line, repeated lines with 1:1 width and spacing ratio, size of 2–25 μm) fabricated by photolithography.99 Neurite extension of neurons was highest on an isolated single 2 μm line, while showing no extensions on flat surfaces and 2 μm wide repeated line patterns. As the width and spacing of line increases, the alignment of neurite outgrowth became more bipolar, in contrast to the multipolar morphologies on the control surface. These results suggest that not only laminin itself but also the patterns of laminin affect the growth cone guidance.
Regeneration: Nanomaterials for Tissue Regeneration
Published in Harry F. Tibbals, Medical Nanotechnology and Nanomedicine, 2017
Oligodendrocytes do not provide the regeneration functions performed by the Schwann cells found in the peripheral system, so regeneration in the central nervous system is inhibited. This is a key distinction between the response to injury in the peripheral nervous system and in the brain. Upon injury to nerve cells within the central nervous system, astrocytes become phagocytic to ingest the injured nerve cells, forming a glial scar which replaces the neurons that cannot regenerate. The glial scar tissue significantly inhibits subsequent axonal elongation and repair.
3D collagen porous scaffold carrying PLGA-PTX/SDF-1α recruits and promotes neural stem cell differentiation for spinal cord injury repair
Published in Journal of Biomaterials Science, Polymer Edition, 2023
Zhixiang Li, Panpan Xu, Lijun Shang, Bingxu Ma, Huihui Zhang, Liangmin Fu, Yuanyuan Ou, Yingji Mao
One of the main obstacles to nerve regeneration is scar tissue formation in the area of injury. Therefore, it is particularly important to reduce scar formation and promote axonal regeneration for functional recovery in rats after SCI. We found that untreated SCI rats displayed a large number of fibrotic glial scars (labeled for laminin) at the injury site, as determined using laminin for immunofluorescence staining (Figure 7A). In contrast, fibrotic glial scars were significantly reduced in the Col-PTX and Col-PTX/SDF-1α groups compared with those in the other groups (Figure 7C). Without the effect of PTX, there was also a significant increase in scar tissue in the Col-SDF-1α and Col groups. This may be due to the ability of PTX to reverse scar tissue formation in the injury microenvironment [11, 43]. Similarly, as shown in Figure 7B, untreated rats with SCI display massive astrocyte (marked by GFAP) accumulation at the injury site when GFAP is used for immunofluorescence staining. Reactive astrocyte proliferation was significantly reduced compared with that in the SCI group (Figure 7D). This phenomenon was particularly evident in the Col-PTX and Col-PTX/SDF-1α groups. Although SDF-1α can facilitate the recruitment of endogenous stem cells to the site of injury and increase the probability of stem cells differentiating into astrocytes, it can reverse the formation of astrocytes in the presence of PTX [44]. Glial scars are formed through the secretion of extracellular matrix by astrocytes. In addition to glial scars, fibrous scars are an important component of scar tissue. The results of laminin-labeled fibrous scarring showed that fibrous scarring was significantly increased in the injured area in the untreated group compared with that in the other groups. The variability in the relative expression of fibrous scarring and astrocytes between the collagen scaffold and Col-SDF-1α groups was mostly observed in the presence or absence of PTX. Therefore, the expression levels of fibrous scars and astrocytes were lower in the Col-PTX group. These results suggest that implanting collagen scaffolds loaded with PLGA-PTX/SDF-1α can promote neuron formation, reduce scar formation, and create a permissive microenvironment for axonal regeneration.