Fast Degrading Bioactive Elastic Scaffold Loaded with Neural Stem Cells Promote Rapid Spinal Cord Regeneration

Despite decades of research, spinal cord injury (SCI) still causes irreparable damage to the human body. Key challenges that must be overcome include the glial scars and inflammatory responses within the injury site that hinder the regeneration and extension of neurons following SCI. Transplantation of neural stem cells (NSCs) represents a promising SCI therapy, but these approaches still do not result in comprehensive recovery due to the limited neuronal differentiation of NCSs. Recently, functional scaffolds have been combined with NSCs to treat SCI. Accordingly, we therefore fabricated elastic poly (sebacoyl diglyceride) (PSeD) scaffolds with similar mechanical properties to natural spinal cord. Then, poly (sebacoyl diglyceride)-isoleucine-lysine-valine-alanine-valine-serine (PSeD-IKVAVS) was coated on the PSeD scaffolds to create a bioactive interface. The resultant scaffolds loaded with NSCs were implanted in a complete transection model of SCI in the rat. Graft integrated well with host spinal cord. Grafted NSCs exhibited neuronal differentiation rather than typical scar and very few inflammatory cells infiltrated the lesion site, leading to the significant functional recovery of the rats in 4 weeks. Next, our in vitro analyses showed that degradation products of PSeD-IKVAVS promoted NSCs differentiate into neurons, inhibited neuronal apoptosis induced by hydrogen peroxide, and alleviated inflammation stimulated by lipopolysaccharide (LPS). Overall, we demonstrated PSeD-IKVAVS scaffold containing the characteristics of suitable mechanical properties, bioactivity and fast degradability combined with NSCs would significantly promote neuronal regeneration indicating a novel approach for effectively treating SCI.