Aligned Biofunctional Electrospun PLGA-LysoGM1 Scaffold for Traumatic Brain Injury Repair

Due to poor regenerative capabilities of the brain, a treatment for traumatic brain injury (TBI) presents a serious challenge to modern medicine. Biofunctional scaffolds that can support neuronal growth, guide neurite elongation, and re-establish impaired brain tissues are urgently needed. To this end, we developed an aligned biofunctional scaffold (aPLGA-LysoGM1), in which poly (lactic-co-glycolic acid) (PLGA) was functionalized with sphingolipid ceramide N-deacylase (SCDase)-hydrolyzed monosialotetrahexosylganglioside (LysoGM1) and electrospinning was used to form an aligned fibrous network. As a ganglioside of neuronal membranes, the functionalized LysoGM1 endows the scaffold with unique biological properties favoring the growth of neuron and regeneration of injured brain tissues. Moreover, we found that the aligned PLGA-LysoGM1 fibers acted as a topographical cue to guide neurite extension, which is critical for organizing the formation of synaptic networks (neural networks). Systematic in vitro studies demonstrated that the aligned biofunctional scaffold promotes neuronal viability, neurite outgrowth, and synapse formation and also protects neurons from pressure-related injury. Additionally, in a rat TBI model, we demonstrated that the implantation of aPLGA-LysoGM1 scaffold supported recovery from brain injury, as more endogenous neurons were found to migrate and infiltrate into the defect zone compared with alternative scaffold. These results suggest that the aligned biofunctional aPLGA-LysoGM1 scaffold represents a promising therapeutic strategy for brain tissue regeneration following TBI.