Bioscaffold-Induced Brain Tissue Regeneration

Abstract

Brain tissue lost after a stroke is not regenerated, although a repair response associated with neurogenesis does occur. A failure to regenerate functional brain tissue is not caused by the lack of available neural cells, but rather the absence of structural support to permit a repopulation of the lesion cavity. Inductive bioscaffolds can provide this support and promote the invasion of host cells into the tissue void. The putative mechanisms of bioscaffold degradation and its pivotal role to permit invasion of neural cells are reviewed and discussed in comparison to peripheral wound healing. Key differences between regenerating and non-regenerating tissues are contrasted in an evolutionary context, with a special focus on the neurogenic response as a conditio sine qua non for brain regeneration. The pivotal role of the immune system in biodegradation and the formation of a neovasculature are contextualized with regeneration of peripheral soft tissues. The application of rehabilitation to integrate newly forming brain tissue is suggested as necessary to develop functional tissue that can alleviate behavioral impairments. Pertinent aspects of brain tissue development are considered to provide guidance to produce a metabolically and functionally integrated de novo tissue. Although little is currently known about mechanisms involved in brain tissue regeneration, this review outlines the various components and their interplay to provide a framework for ongoing and future studies. It is envisaged that a better understanding of the mechanisms involved in brain tissue regeneration will improve the design of biomaterials and the methods used for implantation, as well as rehabilitation strategies that support the restoration of behavioral functions.

Injectable Gelatin Hydrogel Suppresses Inflammation and Enhances Functional Recovery in a Mouse Model of Intracerebral Hemorrhage

“…Interestingly, some cells are infiltrating into the hydrogel on the first day. This phenomenon is similar to the Ghuman's (Ghuman et al, 2018) study, who suggested that these cells are not a brain origin, but likely an immune origin (Modo, 2019), which was responding quickly to the damaged tissue.…”

Advances in Tissue Engineering and Innovative Fabrication Techniques for 3-D-Structures: Translational Applications in Neurodegenerative Diseases

“…The consequences of AIS are hypoxia, an increase in radical oxygen species, and an excessive inflammatory response, which can lead to long-term consequences [ 220 , 221 ]. AIS leads to a loss of brain tissue, which is not regenerated, even if neurogenesis partially occurs, and this is due to the lack of structural support and the fact that the tissue undergoing injury creates a boundary to avoid damage expansion into the healthy tissue [ 222 ]. It is for this reason that bio-scaffolds could prove useful for the therapy of this disease, providing structural support [ 222 , 223 ].…”

“…AIS leads to a loss of brain tissue, which is not regenerated, even if neurogenesis partially occurs, and this is due to the lack of structural support and the fact that the tissue undergoing injury creates a boundary to avoid damage expansion into the healthy tissue [ 222 ]. It is for this reason that bio-scaffolds could prove useful for the therapy of this disease, providing structural support [ 222 , 223 ]. The first evidence that supported the potentiality of scaffold use in AIS was determined after the transplantation of NSCs on polymeric scaffolds, with promising results [ 159 , 160 , 161 , 162 ].…”

“…Other types of cells, such as iPSCs [ 152 , 226 ] and bone marrow mesenchymal stem cells, can be transplanted together with other kinds of scaffolds (e.g., gel-like scaffold from plasma) [ 227 ]. Limitations with these approaches included the non-homogeneity of the scaffold and the need for vascularization [ 222 , 224 , 225 ]. Another scaffolding approach used for the treatment of AIS is 3-D bioprinting [ 228 ].…”

Regenerative Rehabilitation for Stroke Recovery by Inducing Synergistic Effects of Cell Therapy and Neurorehabilitation on Motor Function: A Narrative Review of Pre-Clinical Studies

“…These are more easily able to mimic the appropriate microenvironments of transplanted cells, and therefore can improve survivability and promote differentiation of transplanted cells. Further, if a large section of cerebral parenchyma is lost, the substrates evoking the biological effects of therapy, such as rehabilitation, are also lost, meaning de novo functional tissue is necessary [28,29]. Therefore, optimizing the microenvironment of the transplantation site is considered essential for the success of cell therapy ( Figure 2).…”