Gelatin Methacrylic Acid Hydrogel-Based Nerve Growth Factors Enhances Neural Stem Cell Growth and Differentiation to Promote Repair of Spinal Cord Injury

Mingkui Shen,1,* Lulu Wang,2,* Kuankuan Li,1 Jun Tan,1,3 Zhongxin Tang,1 Xiaohu Wang,4 Hejun Yang1 1Department of Mini-Invasive Spinal Surgery, The Third People’s Hospital of Henan Province, Zhengzhou, Henan, 450006, People’s Republic of China; 2Department of Plastic Surgery, The Third People’s Hospital of Henan Province, Zhengzhou, Henan, 450006, People’s Republic of China; 3Department of Clinical Medicine, Zhengzhou University, Zhengzhou, 450001, People’s Republic of China; 4Department of Orthopedics, Zhengzhou Central Hospital, Zhengzhou, 450007, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hejun Yang, Department of Mini-invasive Spinal Surgery, The Third People’s Hospital of Henan Province, Intersection of Zhengguang Road and Minsheng Road, Jinshui District, Zhengzhou, Henan, 450006, People’s Republic of China, Email [email protected]: The challenge in treating irreversible nerve tissue damage has resulted in suboptimal outcomes for spinal cord injuries (SCI), underscoring the critical need for innovative treatment strategies to offer hope to patients.Methods: In this study, gelatin methacrylic acid hydrogel scaffolds loaded with nerve growth factors (GMNF) were prepared and used to verify the performance of SCI. The physicochemical and biological properties of the GMNF were tested. The effect of GMNF on activity of neuronal progenitor cells (NPCs) was investigated in vitro. Histological staining and motor ability was carried out to assess the ability of SCI repair in SCI animal models.Results: Achieving nerve growth factors sustained release, GMNF had good biocompatibility and could effectively penetrate into the cells with good targeting permeability. GMNF could better enhance the activity of NPCs and promote their directional differentiation into mature neuronal cells in vitro, which could exert a good neural repair function. In vivo, SCI mice treated with GMNF recovered their motor abilities more effectively and showed better wound healing by macroscopic observation of the coronal surface of their SCI area. Meanwhile, the immunohistochemistry demonstrated that the GMNF scaffolds effectively promoted SCI repair by better promoting the colonization and proliferation of neural stem cells (NSCs) in the SCI region and targeted differentiation into mature neurons.Conclusion: The application of GMNF composite scaffolds shows great potential in SCI treatment, which are anticipated to be a potential therapeutic bioactive material for clinical application in repairing SCI in the future.Keywords: hydrogel scaffold, nerve growth factor, spinal cord injury, neuronal regeneration