Multifunctional nanoplatforms for optic nerve regeneration integrating anti-inflammatory, epigenetic, and ionic...

Optic nerve injury represents a common pathological basis underlying various blinding diseases and remains without effective regenerative therapies. The review focuses on three key mechanisms: the inflammatory microenvironment, epigenetic dysregulation, and ionic imbalance, clarifying their temporal dynamics and mutual interactions after injury. It highlights the major factors that limit retinal ganglion cell (RGC) axonal regeneration and synaptic remodeling.Within this framework, representative single and dual mechanism nanodelivery strategies in murine and nonhuman primate models are analyzed, focusing on tissue targeting, therapeutic time windows, and functional outcomes to define their applicability and limitations.The review further summarizes the design principles, pharmacological performance, and engineering optimization of tri mechanistic synergistic platforms that integrate biomimetic membranes, targeting peptides, and stimuli responsive materials. For translational application, an AI assisted framework is proposed for target identification and time window optimization, combined with a closed loop control system that unifies sensing, drug delivery, and evaluation. Key requirements for formulation consistency and quality control are also discussed. The main contribution lies in establishing a unified conceptual framework describing the interplay among the three mechanisms, providing systematic evaluation criteria for nanodelivery strategies, and outlining operational AI driven closed loop platforms with engineering standards. These advances collectively offer a foundation for developing intelligent, precise, and personalized interventions in optic nerve regeneration.