Therapeutic potential of concentrated growth factor for spinal cord injury: Targeting microglial polarization and inflammation regulation

Excessive neuroinflammation following spinal cord injury is a key obstacle that hinders neurological functional recovery. Concentrated growth factor greatly enhances structural repair and functional recovery in damaged spinal cord, providing sustained and spatially specific anti-inflammatory regulation during the acute, subacute, and chronic stages of spinal cord injury. Therefore, this study aimed to evaluate the therapeutic potential of concentrated growth factor in a mouse model of traumatic spinal cord injury and its underlying mechanism. Our results showed that local injection of concentrated growth factor immediately after injury facilitated neurological functional recovery, indicated by improved gait parameters, increased motor evoked potential amplitude, reduced cystic cavities formation, enhanced neuronal survival, strengthened synaptic connections between serotonergic axons and resident neurons, and inhibited collagen deposition forming fibrotic scars. Concentrated growth factor demonstrated spatiotemporally specific anti-inflammatory effects, modulating the immune response by decreasing mediators of inflammation and enhancing anti-inflammatory signaling. The findings indicated that the core mechanism involved regulating microglial polarization states. In both the in vivo spinal cord injury model and an in vitro lipopolysaccharide-stimulated cell model, concentrated growth factor stimulated the polarization of microglial cells away from the inflammation-associated M1 type toward the restorative M2 type. The results further showed that concentrated growth factor inhibited the Toll-like receptor 4/nuclear factor κB and phosphatidylinositol 3-kinase/protein kinase B signaling pathways, suppressing NOD-like receptor family pyrin domain containing 3 inflammasome activation, which may drive the microglial polarization shift and alleviate neuroinflammation. This study focused on the core challenge of secondary neuroinflammation after spinal cord injury, and suggests that concentrated growth factor has potential as a multitarget biological treatment approach. By identifying the key role of microglial polarization in regulation and the core molecular mechanism of simultaneously inhibiting the Toll-like receptor 4/nuclear factor κB and phosphatidylinositol 3-kinase/protein kinase B signaling pathways, our work highlights concentrated growth factor as a potential strategy to achieve neuroprotection, inflammatory regulation and functional reconstruction in spinal cord injury.