Hydrogel Scaffolds: Towards Restitution of Ischemic Stroke-Injured Brain

Abstract

Chronic brain injury following cerebral ischemia is a severe debilitating neurological condition, where clinical intervention is well known to decrease morbidity and mortality. Despite the development of several therapeutic strategies, clinical outcome in the majority of patients could be better improved, since many still face life-long neurological deficits. Among the several strategic options that are currently being pursued, tissue engineering provides much promise for neural tissue salvage and regeneration in brain ischemia. Specifically, hydrogel biomaterials have been utilized to docket biomolecules, adhesion motifs, growth factors, and other proneural cues for stable stem cell encapsulation. Here, we provide an overview of therapeutic applications of hydrogels in stroke treatment. Special focus is given to design considerations for generation of efficient hydrogel systems for neurological applications. Therapeutic applications of hydrogels in stroke as conducive microenvironments for stem cell transplantation and drug delivery have been discussed. Finally, we present our perspectives on clinical translation of hydrogels for neural tissue regeneration.

Applying hiPSCs and Biomaterials Towards an Understanding and Treatment of Traumatic Brain Injury

“…Alternatively, hiPSC-derived cells can be grown as 2D and 3D cultures (brain organoids) that can be used for drug screening or in vitro disease modeling. (Khaing et al, 2014;George and Steinberg, 2015;Boisserand et al, 2016;Nih et al, 2016;González-Nieto et al, 2018;Gopalakrishnan et al, 2019). This is a strategy that has been largely unexplored in the context of TBI treatment but that could have extensive benefits.…”

“…For instance, high molecular weight hyaluronic acid has been shown to decrease microglial inflammatory signaling (Austin et al, 2012). In addition to physical supports, biomaterials can provide trophic support by acting as a depot for soluble factors either delivered with the biomaterial (Wang et al, 2012;Cook et al, 2017;Nih et al, 2018) or secreted by infiltrating cells, thereby maintaining a high concentration of those factors where they are most needed (Pakulska et al, 2012;Khaing et al, 2014;George and Steinberg, 2015;Boisserand et al, 2016;Nih et al, 2016Nih et al, , 2018González-Nieto et al, 2018;Gopalakrishnan et al, 2019). In general, biomaterials have garnered significant interest as drug delivery vehicles, for their abilities to provide local, controlled release of a therapeutic over time.…”

“…Other issues faced by stroke therapies that are pertinent to TBI include the dispersion away from the transplantation site and low survival rates of exogenous SCs, the low numbers of migrating endogenous SCs, and the low levels of differentiation and integration with existing tissue. These issues are shared by TBI stem cell therapies, and attempts are being made in the context of stroke to address all of them via the incorporation of biomaterials (Nih et al, 2016;González-Nieto et al, 2018;Gopalakrishnan et al, 2019;Ho et al, 2019;Obermeyer et al, 2019). Biomaterials have been used in stroke treatments as scaffolds to support endogenous cell infiltration (Ghuman et al, 2016(Ghuman et al, , 2017Nih et al, 2017), and as delivery vehicles for small molecules (Wang et al, 2012;Cook et al, 2017;Nih et al, 2018) and SCs with encouraging results (Moshayedi and Carmichael, 2013;Lam et al, 2014;Moshayedi et al, 2016;Nih et al, 2018;Payne et al, 2019).…”

Effects of Recombinant Spidroin rS1/9 on Brain Neural Progenitors After Photothrombosis-Induced Ischemia

“…The difficulty of implementation of primary neuroprotection is the limited length of the therapeutic window, which cannot go beyond 5-6 h after damage. On the other hand, approaches aimed at enhancing brain plasticity, i.e., those considering effects on the damaged brain independent on the pharmacologic therapeutic window, such as stem cell or extracellular vesicle transplantation (Bang and Kim, 2019;Borlongan, 2019), or scaffold transplantation (Gopalakrishnan et al, 2019) have shown high therapeutic efficiency.…”

An injectable refrigerated hydrogel for Inducing local hypothermia and neuroprotection against traumatic brain injury

“…Injectable hydrogels can be used for the local delivery of drugs and have been widely used for the treatment of brain diseases (TBI and stroke) due to their good biocompatibility, biofunctionality, and ability to form via an in situ gelling process (21,22). The hydrogels themselves can be used as carriers to load various drugs, and the drug utilization e ciency can be improved while prolonging the action time of the drug by injecting it in situ or directly on the tissue surface (20).…”