A Neuroprotective Sericin Hydrogel As an Effective Neuronal Cell Carrier for the Repair of Ischemic Stroke

Abstract

Ischemic stroke causes extensive cellular loss that impairs brain functions, resulting in severe disabilities. No effective treatments are currently available for brain tissue regeneration. The need to develop effective therapeutic approaches for treating stroke is compelling. A tissue engineering approach employing a hydrogel carrying both cells and neurotrophic cytokines to damaged regions is an encouraging alternative for neuronal repair. However, this approach is often challenged by low in vivo cell survival rate, and low encapsulation efficiency and loss of cytokines. To address these limitations, we propose to develop a biomaterial that can form a matrix capable of improving in vivo survival of transplanted cells and reducing in vivo loss of cytokines. Here, we report that using sericin, a natural protein from silk, we have fabricated a genipin-cross-linked sericin hydrogel (GSH) with porous structure and mild swelling ratio. The GSH supports the effective attachment and growth of neurons in vitro. Strikingly, our data reveal that sericin protein is intrinsically neurotrophic and neuroprotective, promoting axon extension and branching as well as preventing primary neurons from hypoxia-induced cell death. Notably, these functions are inherited by the GSH's degradation products, which might spare a need of incorporating costly cytokines. We further demonstrate that this neurotrophic effect is dependent on the Lkb1-Nuak1 pathway, while the neuroprotective effect is realized through regulating the Bcl-2/Bax protein ratio. Importantly, when transplanted in vivo, the GSH gives a high cell survival rate and allows the cells to continuously proliferate. Together, this work unmasks the neurotrophic and neuroprotective functions for sericin and provides strong evidence justifying the GSH's suitability as a potential neuronal cell delivery vehicle for ischemic stroke repair.

Toward Customized Extracellular Niche Engineering: Progress in Cell‐Entrapment Technologies

“…Studies need to include unconventional protein‐based matrix molecules. One such molecule sericin, derived from silk worms, has shown to promote axonal growth of primary neuronal cells, offering neuroprotection by modulating apoptosis signaling pathway …”

Tissue engineering scaffolds in the treatment of brain disorders in geriatric patients

“…Wang and co‐workers developed a genipin‐crosslinked sericin hydrogel (GSH), and seeded it with primary cortical neurons (PCN). The researchers observed that the degradation product, Lkb1‐Nuak1 , of the scaffold was neurotropic; that is, it promoted neural growth . The scaffold was also observed to possess neuroprotective properties, thus improving neural survivability in vivo.…”

The Action of Sericin Protein on Initial Nerve Repair, Associated or Not With Swimming in Wistar Rats

“…11 Sericin has been shown to have an influence on the regeneration of cartilaginous tissue, favoring cell proliferation, 12 accelerating cutaneous tissue regeration, 13 acting on the healing process and possibly leading to lower levels of inflammatory mediators. 14,15 Wang et al 16 demonstrated its neuroprotector effect in neuronal repair, promoting the growth of neurons in vitro. In addition, other potential effects have made sericin the focus of interest by several segments, given its possible uses.…”