NSC-derived extracellular matrix-modified GelMA hydrogel fibrous scaffolds for spinal cord injury repair

Abstract

Cell-derived extracellular matrix (ECM) has been applied in spinal cord injury (SCI) regeneration because of its various biological functions. However, insufficient mechanical properties limit its wide application. Herein, we developed GelMA/ECM hydrogel fibrous scaffolds (GelMA/ECM scaffolds) that can recruit and enhance the differentiation of neural stem cells (NSCs) by electrospinning and decellularization techniques. Moreover, the GelMA/ECM scaffolds had good mechanical properties and reinforced cell adhesion and proliferation. Compared to GelMA hydrogel fibrous scaffolds (GelMA scaffolds), GelMA/ECM scaffolds promoted more NSCs toward neurons by markedly enhancing the expression of MAP-2 and Tuj-1 and decreasing GFAP expression. In addition, the GelMA/ECM scaffolds significantly reduced the proportion of M1-phenotype macrophages, which is favorable for SCI repair. In vivo, the GelMA/ECM scaffolds recruited NSCs at the injured site, promoted neuron regeneration, and reduced the formation of glial scars and the inflammatory response, which further led to a significant improvement in the functional recovery of SCI. Therefore, this scaffold shows potential in regenerative medicine, mainly in SCI.

The impact of electrical stimulation protocols on neuronal cell survival and proliferation using cell-laden GelMA/graphene oxide hydrogels

“…Furthermore, the similarities between the GelMA structure and neuronal extracellular matrix might be helping the PC12s to survive and proliferate. 51–53 Even though GelMA is considered a non-conductive material, the current going through the hydrogels is related to the dispersion of ions, from the proliferation media, into the GelMA. The absence of cell death on GelMA/GO samples may be related to the electrochemical properties of GO, which might help to distribute the charge through the hydrogel homogeneously.…”

Hydrogel encapsulated stem cells facilitate successful repair after spinal cord injury in rats and monkeys

“…Scaffolds for cell encapsulation need to con ne grafted cells to the injury site, minimize hostile effects of the SCI physiological environment, be biocompatible and biodegradable, safe, and have low immunogenicity 19 . Gelatin methacrylol (GelMA) and methacrylated hyaluronic acid (HAMA) meet these requirements and are widely used as tissue engineering scaffolds 35,36 . Combining hydrogels with microspheres can further provide a larger surface area to carry more cells and a microenvironment that supports cell survival, nutrient exchange and waste delivery.…”

Injectable, Hierarchically Degraded Bioactive Scaffold for Bone Regeneration

“…In most cases, the defect is unable to be resolved via self-repair. Thus, there is an urgent need for bone repair implants to aid in repairing bone defects, an ongoing challenge in clinical treatment. − Autogenous bone transplantation is currently the most effective strategy for bone regeneration and has excellent osteoconductivity and osteoinductivity . Despite this, it is not widely used in clinics due to latent infection, nerve damage, and chronic pain at the donor site .…”

“…1−3 Autogenous bone transplantation is currently the most effective strategy for bone regeneration and has excellent osteoconductivity and osteoinductivity. 4 Despite this, it is not widely used in clinics due to latent infection, nerve damage, and chronic pain at the donor site. 5 Limited sources, immune rejection, and disease spread greatly hinder the clinical application of allogeneic bone.…”