MgFe-LDH-doped GelMA hydrogel scaffold repaired spinal cord injury via immunoregulation and enhancement of neuronal differentiation

Spinal cord injury (SCI) is a traumatic condition of the nervous system that leads to severe disability. Its poor prognosis is largely attributed to uncontrolled inflammation and the intrinsically limited regenerative capacity of the spinal cord, which together severely restrict functional recovery. Hydrogel-based scaffolds represent a prospective strategy for SCI repair, offering structural support and a conducive microenvironment for regeneration. Here, we developed a gelatin methacrylate (GM) hydrogel scaffold incorporating MgFe-layered double hydroxide (LDH) nanoparticles functionalized with brain-derived neurotrophic factor (BDNF). This multifunctional GM-BDNF-LDH scaffold enables sustained release of BDNF, which promotes neuronal survival and regeneration, while LDH contributes additional therapeutic benefits through immunomodulation and neurogenic support. In both in vivo and in vitro experiments, LDH promoted the differentiation of neural stem cells (NSCs) while suppressing the expression of M1 markers and promoting the expression of M2 markers in microglia. Furthermore, the functional scaffold significantly improved motor function restoration, inflammation suppression, and neural differentiation in rats. Together, these results demonstrate that the LDH-functionalized scaffold we proposed can simultaneously modulate the immune microenvironment and promote neuronal regeneration, offering a potential treatment strategy for SCI recovery.