An injectable and adaptable hydrogen sulfide delivery system for modulating neuroregenerative microenvironment
Xianzhen Dong, Hao Zhang, Ping Duan, Kun Liu, Yifeng Yu, Wenying Wei, Weixing Wang, Yuhang Liu, Qiang Cheng, Xinyue Liang, Yuanfang Huo, Lesan Yan, Aixi Yu, Honglian Dai
Abstract
Peripheral nerve regeneration is a complex physiological process. Single-function nerve scaffolds often struggle to quickly adapt to the imbalanced regenerative microenvironment, leading to slow nerve regeneration and limited functional recovery. In this study, we demonstrate a “pleiotropic gas transmitter” strategy based on endogenous reactive oxygen species (ROS), which trigger the on-demand H 2 S release at the defect area for transected peripheral nerve injury (PNI) repair through concurrent neuroregeneration and neuroprotection processing. This H 2 S delivery system consists of an H 2 S donor (peroxyTCM) encapsulated in a ROS-responsive polymer (mPEG-PMet) and loaded into a temperature-sensitive poly (amino acid) hydrogel (mPEG-PA-PP). This multi-effect combination strategy greatly promotes the regeneration of PNI, attributed to the physiological effects of H 2 S. These effects include the inhibition of inflammation and oxidative stress, protection of nerve cells, promotion of angiogenesis, and the restoration of normal mitochondrial function. The adaptive release of pleiotropic messengers to modulate the tissue regeneration microenvironment offers promising peripheral nerve repair and tissue engineering opportunities.