Oriented porous microtubules combined with CNTF-delivery directional guide axonal regeneration after traumatic optic neuropathy.

Neuroinflammation microenvironment and retinal ganglion cell (RGC) apoptosis are two critical barriers to axonal regeneration following traumatic optic neuropathy (TON). To overcome these challenges, we developed an innovative dual drug delivery strategy utilizing oriented porous nanofiber (OF) and ciliary neurotrophic factor (CNTF)-loaded delivery systems, aiming to promote axonal regeneration and restore RGC survival. Cerium oxide nanoparticles (Ce NPs) were physically mixed with poly(L-lactic acid)/polycaprolactone (PLA/PCL) solution to prepare oriented porous nanofibers (OF-Ce) via electrospinning and solvent evaporation techniques. The aligned porous nanofiber architecture supports drug loading, guides cell directional growth, and integrates Ce NPs properties to modulate the neuroinflammatory environment. Subsequently, neural stem cell-derived exosomes (NSC Exo) were applied onto the porous OF-Ce nanofiber microtubule (OF-Ce/Exo), stabilizing exosomes, improving hydrophilicity, and significantly reducing neuroinflammation while inhibiting glial scar formation. Importantly, these OF-Ce/Exo microtubules effectively guide the directional growth and migration in various cell types. Furthermore, CNTF was encapsulated into PEGylated mesoporous silica nanoparticles (PMSN-CNTF NPs) for sustained release, reducing PC12 cell apoptosis in inflammatory conditions. Notably, in situ implantation of OF-Ce/Exo microtubules, coupled with intravitreal injection of PMSN-CNTF NPs, significantly promoted axonal regeneration and alleviated RGC death in a rat optic crush model, highlighting their potential for treating TON.