Fabrication of neuroprotective silk-sericin hydrogel: potential neuronal carrier for the treatment and care of ischemic stroke

Abstract Ischemic stroke results in severe disabilities due to extensive cellular loss and the resulting impairment of brain functions. Current methods for regenerating brain tissue are ineffective. Stroke treatment requires innovative therapeutic techniques that are both safe and effective. For neuronal repair, a promising alternative is using a hydrogel-based tissue engineering technique that delivers neurotrophic cytokines and cells to injured sites. However, the limited encapsulation effectiveness, less in vivo cell survival ratio and cytokine loss make this strategy difficult to implement. We aim to design a biomaterial that can efficiently construct a matrix enriching the survival of cells and minimizing loss in vivo cytokines to overcome these constraints. We report the development of genipin conjugated sericin hydrogels (Gen-SH) with a high porous morphology and a moderate swelling rate utilizing sericin, a natural silk protein. In vitro, Gen-SH aids in the attachment and development of neurons. Our results indicate that sericin is inherently neuroprotective and neurotrophic, branching and publicizing axon extension and avoiding hypoxia-induced cell death in primary neurons. Notably, the breakdown products of Gen-SH inherit these capabilities, saving the expense of cytokines. Furthermore, we show that the Lkb1–Nuak1 pathway is required for this neurotrophic impact, whereas the Bcl-2/Bax protein ratio is necessary for the neuroprotective effect. Transplanted in vivo, Gen-SH has a high percentage of cell survival and promotes cell proliferation. Taking all this information into account, it's clear that Gen-SH can serve as a viable carrier for treatment and care for ischemic stroke healing, both in terms of delivering neuronal cells and protecting them from oxidative damage.