Photocrosslinkable chitosan based hydrogels for neural tissue engineering

Abstract

Hydrogel based scaffolds for neural tissue engineering can provide appropriate physico-chemical and mechanical properties to support neurite extension and facilitate transplantation of cells by acting as ‘cell delivery vehicles’. Specifically, in situ gelling systems such as photocrosslinkable hydrogels can potentially conformally fill irregular neural tissue defects and serve as stem cell delivery systems. Here, we report the development of a novel chitosan based photocrosslinkable hydrogel system with tunable mechanical properties and degradation rates. A two-step synthesis of amino-ethyl methacrylate derivitized, degradable, photocrosslinkable chitosan hydrogels is described. When human mesenchymal stem cells were cultured in photocrosslinkable chitosan hydrogels, negligible cytotoxicity was observed. Photocrosslinkable chitosan hydrogels facilitated enhanced neurite differentiation from primary cortical neurons and enhanced neurite extension from dorsal root ganglia (DRG) as compared to agarose based hydrogels with similar storage moduli. Neural stem cells (NSCs) cultured within photocrosslinkable chitosan hydrogels facilitated differentiation into tubulin positive neurons and astrocytes. These data demonstrate the potential of photocrosslinked chitosan hydrogels, and contribute to an increasing repertoire of hydrogels designed for neural tissue engineering.

Physiochemical and optical study of chitosan–terephthaldehyde derivative for biomedical applications

“…Crosslinkers are molecules with at least two reactive functional groups that allow the formation of bridges between polymeric chains [15]. Various methods have been developed for the cross-linking of chitosan biopolymer, which result in gel formation [16][17][18][19][20][21]. Cross-linking chitosan has been reported with small molecular dialdehydes, such as glyoxal and glutaraldehyde to create directly hydrogels [22][23][24].…”

Chitosan Hydrogels for Regenerative Engineering

“…Photocrosslinked chitosan hydrogels are also employed in neural tissue engineering. Reports suggest that these hydrogels can enhance the differentiation and extension of neuritis and neural stem cells [120]. Chitosan hydrogels are also implemented for neurosurgical applications.…”

Photopolymerized Injectable Water-soluble Maleilated Chitosan/ Poly(ethylene glycol) Diacrylate Hydrogels as Potential Tissue Engineering Scaffolds

“…Photopolymerized injectable hydrogels are extensively investigated for various tissue engineering applications [1,2], primarily due to their unique merits such as direct application to the targets in a minimally invasive manner, spatially-controlled fast gel transition at physiological condition [3], and more importantly, local delivery of growth factors or cells to promote tissue repair rapidly by mimicking natural tissues environments [4]. Several synthetic and natural polymers, such as poly (ethylene glycol) [5], hyaluronic acid [6], alginate [7] and chitosan, have been explored to synthesize photocrosslinked injectable hydrogels.…”

“…However, these synthesis protocols normally involve multistep chemical modification, which could lead to relatively low yields of final products. Besides, azo-derivitized chitosan hydrogels was found to have high storage moduli or pore sizes that are not ideal for neurite out growth [1]. A simple one-step modification of chitosan, photocrosslinkable water-soluble maleic chitosan (MCS), was also prepared [16].…”

“…The mixture was precipitated by acetone and then dialyzed (membrane molecular weight cut-off 12000 g·mol -1 ) against water for 2 days and lyophilized to obtain pure MCS. 1 H NMR spectrum was recorded on a Bruker AV 400 NMR instrument.…”