A Novel 3D-Printed Implant for Neuroglial Regeneration: Advancing Central Nervous System Recovery

Abstract

Neurological disorders, including traumatic brain injuries (TBIs), spinal cord injuries (SCIs), peripheral nerve injuries (PNIs), and neurodegenerative disorders (NDs), affect 1 in 6 individuals globally. The central nervous system (CNS) has a limited regenerative capacity following injury or disease leaving long-lasting cognitive dysfunction. The field’s current gold standard, nerve grafts, poses risks of infection, functional limitations, and substantial costs. Neuroglia, specifically astrocytes with distinct A1 and A2 categories play a crucial role in homeostasis and neurogenesis in the CNS. A1 reactive astrocytes induce neuron death while A2 reactive astrocytes promote neuron growth. This investigation aimed to enhance CNS recovery by developing a 3D-printed hydrogel-integrated scaffold. A novel scaffold was printed with polyethylene terephthalate glycol (PETG) chemically crosslinked with a gelatin/chitosan/silk fibroin hydrogel incorporated with nerve growth factor (NGF) and chondroitinase ABC (ChABC) to stimulate nerve growth and mitigate tissue scarring. Biomaterial and biological characterization was done against the positive control, a murine nerve graft. An SEM analysis indicated a 75µm pore size and a porosity appropriate for astrocyte growth. A rheological frequency sweep found a complex modulus up to 162 Pascals. The implant absorbed water up to 92% of its dry mass and exhibited slow degradability. Cell growth increased 167% within a 3-day period with 94% cell viability. The implant also displayed a significantly lower amount of neuroinflammatory markers and axon growth of 45µm. Overall, this novel integrated implant holds promise for CNS regeneration and neural engineering applications, offering a biocompatible, functional, cost-effective alternative to current standards.