(392) Research Progress of Regenerative Therapy in the Treatment of Neurogenic Erectile Dysfunction

Introduction Cavernous nerve injury-induced erectile dysfunction (CNIED) is a common complication following prostate cancer treatment, with traditional therapies like phosphodiesterase type 5 inhibitors (PDE5is) showing limitations due to their dependence on neural integrity and the nitric oxide (NO) pathway. Regenerative therapies, which aim to promote nerve regeneration, angiogenesis, and improvement of the penile cavernous microenvironment, have emerged as promising strategies for long-term alleviation or even radical cure of CNIED. This review summarizes the current progress, mechanisms, and challenges of various regenerative approaches for CNIED. Objective This review aims to comprehensively summarize the therapeutic strategies and underlying mechanisms of regenerative therapies for CNIED, including stem cell therapy, platelet-rich plasma therapy, micro-energy therapy, tissue engineering, small-molecule drugs, and photobiomodulation. It also seeks to discuss the current research progress, developmental directions, practical challenges, and limitations of these strategies, while proposing suggestions and prospects for future development. Methods This review is based on the retrieval and analysis of English original articles and narrative reviews published in PubMed databases up to July 2025. The keywords for retrieval include regenerative therapy, low-intensity extracorporeal shockwave therapy, low-intensity pulsed ultrasound, stem cell therapy, platelet-rich plasma, nerve transplantation, nerve regeneration, tissue engineering, biomaterials, erectile dysfunction, cavernous nerve injury, prostatectomy, and photobiomodulation. It is not a systematic review or meta-analysis of the topic, but includes clinical trials and animal model studies. The review aims to summarize the known therapies and research progress of male erectile dysfunction after cavernous nerve injury, focus on discussing penile rehabilitation strategies, explain the mechanisms of various regenerative therapies, and prospect the future development directions of related technologies. Results Regenerative therapies for CNIED involve multiple strategies with distinct mechanisms:  Stem cell therapy acts via multi-differentiation potential and paracrine effects, with enhanced efficacy when combined with biomaterials or drugs. Platelet-rich plasma (PRP) promotes repair through autologous growth factors, showing clinical benefits in improving erectile function scores. Micro-energy therapies exert effects via mechanical stimulation, aiding neuroregeneration and angiogenesis. Tissue engineering and biomaterials provide structural support and drug delivery, with proven efficacy in animal models. Other approaches, such as photobiomodulation, exhibit potential in preclinical studies. However, most therapies remain in preclinical stages, facing challenges like inconsistent protocols, unclear mechanisms, and limited long-term safety data. Conclusions Although currently facing multiple challenges of mechanism, transformation and standardization, with the deepening of multidisciplinary cross integration, regenerative therapy is expected to gradually achieve clinical transformation, providing core support for improving the quality of life of cnied patients. Disclosure No