Fabrication of RADA32/Ngf_EE/MSCs composite hydrogel and its protective mechanism against radiation-induced ototoxicity.

Source: PubMed, NCBI / U.S. National Library of Medicine

Radiotherapy is a cornerstone in head and neck tumor treatment, but 47.4% of treated patients experience radiation-induced hearing loss despite precise techniques. To address inner ear barriers and drug delivery limits, we developed an injectable peptide self-assembling hydrogel-RNM-composed of RADA32, Ngf_EE, and mesenchymal stem cells (MSCs). This system forms stable nanofibrous networks, is efficiently endocytosed by hair cells, and enhances MSC activity. RNM significantly reduces radiation-induced reactive oxygen species (ROS) and inflammation, thereby decreasing cell apoptosis and DNA damage. In irradiated mice, minimally invasive intratympanic injection of RNM partially repaired cochlear outer hair cell and spiral ganglion structural damage and restored auditory function. This protection is mediated by inhibiting the NF-κB signaling pathway and reversing M1 polarization of cochlear macrophages. Additionally, intratympanic delivery showed good biosafety. In conclusion, RNM exerts a dual mechanism of immunomodulation and enhanced inner ear cell viability, effectively protecting against radiation-induced inner ear injury, with promising clinical translation potential.