Photo‐Responsive H2S Composite System Regulates the Nerve Regeneration Microenvironment Through Multiple Pathways

After injury, the imbalance of the regeneration microenvironment caused by inflammation, oxidative stress, insufficient neurovascularization, and inadequate energy supply affects nerve regeneration. Drug-delivery nerve conduits play a role in repairing the regenerative microenvironment. However, traditional drugs often fail to cross the blood-nerve barrier and lack multifunctionality, limiting the effectiveness of conduit therapy. Therefore, it is necessary to construct a multifunctional conduit that regulate the regeneration microenvironment timely and effectively. Herein, a photo-responsive hydrogen sulfide (H₂S) composite nerve conduit, artificially controlled H₂S release, is developed. A new structure of zinc-citric acid organic metal framework (Zn-CA MOFs) is utilized to improve its drug loading rate, achieving the joint regulation of the nerve regeneration microenvironment by H₂S and Zn²⁺. In addition, RGD modification of polyester amide (P(CL-MMD-MAC)-RGD)) combined with aligned structure is used to improve the performance of the conduit. Relevant results demonstrate that H₂S and Zn²⁺ can regulate inflammatory response and oxidative stress and promote mitochondrial function recovery and angiogenesis. Furthermore, the aligned structure can promote cell adhesion and guide cell directed migration. Overall, this study provides a method of combining gas neurotransmitters with ions to improve the nerve regeneration microenvironment, accelerate nerve regeneration, and restore motor function.