Table 1.

Hydrogels used for SCs/SCLCs transplantation.

	Biomaterial	Origin	Advantages	Disadvantages	Application
Protein-based hydrogel	Collagen	Animal tissues, a structural protein of the ECM	Easy to be isolated, purified, and can spontaneously form hydrogels Biocompatible and biodegradable Provide essential ECM molecules to support cellular functions Nanofibrous structures	Potential immunoreaction Inadequate mechanical property Rapid degradation in vivo	The raw material of FDA-approved nerve conduits Promote cellular survival, retention, and neurite regeneration as a cell carrier (Guan et al., 2013; Georgiou et al., 2015)
	Gelatin/GelMA	A product of hydrolyzed collagen	Good biocompatibility, degradability, low immunogenicity, and stable mechanical properties.	Potential damage to the transplanted cells during UV light crosslinking	The base of bio-ink in 3D bioprinting and cell encapsulation (Zhao et al., 2016; Sun et al., 2018; Xiao et al., 2019).
	Fibrin	An insoluble protein polymer of plasmic proteins	Highly compatible with blood and tissues Inhibit the expression of myelin and keep SCs in a non-myelin state to induce regeneration through ERK1/2 phosphorylation	Poor stiffness, fast degradation, and the risk of transmitting blood disease.	Enhanced SCs viability and nerve regeneration by introducing fibrin hydrogel (Schuh et al.) Promote EMSC differentiation into SCLCs (Chen et al., 2015).
Polysaccharides-based hydrogel	HA	Animal tissues, rich in eyes and joints, a glycosaminoglycan type of ECM content	Biocompatible and biodegradable Easy to be chemical functionalized Promote cell proliferation by binding to CD44 receptor on cell surface Shear-thinning	Poor cell attachment property due to the high-water retention rate	Combined with alginate hydrogel to promote SCs survival and proliferation (Wang et al., 2013) Provide injectability, printability, and bioactivity to protect SCs and SCLCs during transplantation (May et al., 2018; Ho et al., 2019)
	Alginate	A linear polysaccharide extracted from brown algae	Non-immunogenicity, slow degradation properties and high hydrophilicity Quickly and reversibly crosslinked by Ca2+	Need biological modification	Bridging materials for both spinal cord and peripheral nerve injury repair (Mosahebi et al., 2002; Wu et al., 2020).
Decellularized matrix-based hydrogel	Tissue-derived dECM hydrogels	The native mammal tissues/organs	Retain large amount of ECM components, and recapitulate the biological characteristics of native ECM Biocompatible, biodegradable, and bioactive	Lower moduli, difficult to be modified Unknown immunoreaction in human	Peripheral nerve-derived dECM hydrogel significantly improved SCs survival and axonal remyelination (Cerqueira et al., 2018)
	Matrigel	Cultured EHS tumor cell lines	Excellent biological activity in promoting cell growth and proliferation.	Potential risk in clinical translation	Base material for cell culture (Kamada et al., 2005; Lopatina et al., 2011).
Synthetic hydrogels	PEG		Non-toxicity, good biocompatibility, low protein adsorption, and noninflammatory invasion. Reduces ROS to protect neurons.	Hydrophilic and biological inert Undegradable	Modified with RGD peptides or other functional peptides to support NSCs and SCs survival (Franco et al., 2011; Marquardt et al., 2020)
	PHEMA		Porosity and moduli are easily manipulated	Bio-inert	Supporting materials of the multicomponent hydrogels (Hejcl et al., 2010)