Review articleThe use of bioactive matrices in regenerative therapies for traumatic brain injury
Graphical Abstract
Introduction
Traumatic brain injury (TBI) is one of the leading causes of death and disability in industrialized countries, occurring predominantly in young adults. Survivors of severe TBI have a shorter life expectancy, in addition to permanent functional impairments that can altogether, impose significant socioeconomic consequences on the individual [1]. The prognosis for TBI remains poor due to the lack of viable treatments, which are predominantly aimed at supporting vital functions of the patient and minimizing neural tissue loss. Clinical trials for neuroprotective compounds, hypothermia treatment and decompressive craniectomy have not only failed to show efficacy in improving functional outcome, but have also exacerbated the neuronal loss in some cases [2], [3], [4], [5], [6]. While these findings highlight the need for therapeutics that can rescue neurological functions post-TBI, they also suggest that treatment strategies focused on providing neuroprotection are not sufficient to attenuate the debilitating effects of severe intracerebral injuries. Reconstructing functional neural circuitry via cell-based therapies therefore represents a viable, alternative therapeutic strategy to improve clinical outcome.
Section snippets
Pathophysiology
TBI occurs via an external mechanical force, leading to tissue strain or deformation. The primary brain tissue damage can cause contusions, haematoma and diffuse axonal injuries [7]. This results in immediate cell death and the initiation of secondary cascades involving physiological changes that can develop over an extended period of time after the injury. It induces secondary brain tissue damage that involves processes such as necrosis, excitotoxicity, oxidative stress, vascular disruption
Cell-based therapies
Stem cell-based restorative strategies are directed at facilitating cell replacement and regeneration at the injury site by providing a source of specific cell types and trophic support, and shaping a permissive microenvironment at the injury site for neural repair to occur [9]. Neural transplantation has been explored using different cell types, such as embryonic stem cells (ESCs), mesenchymal stem cells (MSCs), induced pluripotent stem cells (iPSCs) and their derivatives to treat CNS injuries
Neurogenesis
The potential for neural regeneration after an insult via endogenous recovery mechanisms in the adult brain has been extensively studied with neurogenesis in the adult mammalian brain first observed in the 1960s [55,56]. Adult neurogenesis is confined to stem-cell niches within the brain, namely the subgranular zone in the hippocampal dentate gyrus (DG) and the subventricular zone (SVZ) in the lateral ventricles (Refer to Fig. 1). These neurogenic regions contain multipotent NPSCs that are
Bioactive matrices for neural repair in TBI
Neural tissue engineering has been a prominent area of research as a viable strategy to treat CNS injuries and diseases [87,88]. Recent advances in the field have demonstrated the potential for bioactive matrices to augment neural repair and regeneration by providing physical and biochemical support for cellular migration and survival, and an alternative drug administration route. Bioactive matrices can be synthesized via the use of natural and/or synthetic polymers, which are aimed at
Conclusion
Advances in biomaterial science have been applied to neural tissue engineering by complementing cell-based therapies in regenerative medicine. While stem cell transplantation has been explored extensively, the capacity for endogenous reparative mechanisms within the brain to facilitate functional recovery following a neural injury remains elusive. This review has examined desirable traits in hydrogels used for the enhancement of reparative processes involving endogenous NPSCs in the brain, in
Declaration of Competing Interest
The authors declare no conflict of interest.
Acknowledgments
All authors contributed equally to this work.
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