A Polydopamine-coated Engineered Type II Collagen Scaffold for Motor Neuron Organization and Spinal Cord Injury Regeneration.

Spinal cord injury (SCI) leads to severe motor neuron depletion and glial scar formation, limiting endogenous regeneration and motor functional recovery. While engineered collagen scaffolds offer a promising strategy for supporting neural repair, the optimal scaffold composition and functionalization remain to be explored. This study investigates the efficacy of a novel polydopamine-coated engineered type II collagen (Col 2-PDA) scaffold and evaluates its efficacy for inducing differentiation of motor neural progenitors (MNPs) into motor neurons and for promoting motor functional recovery in the SCI model. In vitro, the Col 2-PDA scaffolds significantly enhance MNPs proliferation and differentiation into motor neurons while reducing apoptosis compared to crosslinked type I collagen controls. In the transected SCI model, hindlimb motor function improved. The Col 2-PDA scaffolds attenuate astrogliosis, suppress glial scar formation, and potently modulate the local immune response, as evidenced by an increased proportion of CD206+ macrophages. Critically, the lesion site in the Col 2-PDA group exhibits robust expression of the axonal regeneration marker GAP43, along with the formation of SYP+ new synaptic connections. Collectively, these findings prove that the engineered Col 2-PDA scaffolds provide a conducive microenvironment for motor neuron organization and that PDA functionalization synergistically enhances the therapeutic potential by mitigating inflammation, driving anti-inflammatory macrophage polarization, and facilitating neurogenesis and axon regeneration. Thus, the Col 2-PDA scaffolds represent a multifunctional platform for advanced neural tissue engineering and SCI treatment.