Ultrasound-driven wireless piezoelectric hydrogel synergizes with cotransplantation of NSCs–hUCMSCs for structural and functional recovery in spinal cord injury
Spinal cord injury (SCI) is a devastating condition of the central nervous system, characterized by disrupted regulation of the immune microenvironment and the loss of electrical signaling, which poses significant challenges to repair. Neural stem cells (NSCs) have the potential to promote functiona...
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Elsevier
2025-06-01
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2590006425003655 |
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| author | Hao Zhong Mi Zhou Junrui Guo Danyang Chen Cong Xing Song Liu Hongjiang Yang Hongpeng Ma Qi Zhang Jianhai Yang Shiqing Feng Guangzhi Ning |
| author_facet | Hao Zhong Mi Zhou Junrui Guo Danyang Chen Cong Xing Song Liu Hongjiang Yang Hongpeng Ma Qi Zhang Jianhai Yang Shiqing Feng Guangzhi Ning |
| author_sort | Hao Zhong |
| collection | DOAJ |
| description | Spinal cord injury (SCI) is a devastating condition of the central nervous system, characterized by disrupted regulation of the immune microenvironment and the loss of electrical signaling, which poses significant challenges to repair. Neural stem cells (NSCs) have the potential to promote functional recovery after SCI; however, their therapeutic potential is limited by poor survival, restricted proliferation, and suboptimal differentiation. Human umbilical cord-derived mesenchymal stem cells (hUCMSCs) possess powerful paracrine and immunomodulatory properties, providing a supportive niche that improves the engraftment and function of NSCs. Recently, piezoelectric materials have attracted increasing attention for their ability to convert mechanical energy into electrical signals, thus providing a noninvasive, wireless alternative to traditional electrode-based therapies for neural regeneration. In this study, we investigated the synergistic effects of NSCs and hUCMSCs, focusing on how hUCMSCs direct NSC differentiation and the mechanisms underlying this action. We also introduce an ultrasound-driven wireless piezoelectric hydrogel, which generates electrical signals through the piezoelectric effect. In vitro, wireless electrical stimulation activated primary cortical neurons, stimulated axonal growth, and promoted neuronal plasticity through the Piezo1 channel and downstream CREB/CAMKII signaling pathways. In a rat SCI model, wireless piezoelectric hydrogel synergized with cotransplanting NSCs–hUCMSCs and modulated the immune microenvironment during the acute phase, thereby restructuring scar cavities during the chronic phase, suppressing scar formation, accelerating neurogenesis, and facilitating axonal regeneration. These results emphasize the potential of synergizing stem cell therapies with wireless piezoelectric stimulation as a promising strategy for SCI repair, providing novel insights into the clinical translation of regenerative treatments. |
| format | Article |
| id | doaj-art-ad4389870ab64f99a9ce014d4c56bb7a |
| institution | OA Journals |
| issn | 2590-0064 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Materials Today Bio |
| spelling | doaj-art-ad4389870ab64f99a9ce014d4c56bb7a2025-08-20T01:55:52ZengElsevierMaterials Today Bio2590-00642025-06-013210180510.1016/j.mtbio.2025.101805Ultrasound-driven wireless piezoelectric hydrogel synergizes with cotransplantation of NSCs–hUCMSCs for structural and functional recovery in spinal cord injuryHao Zhong0Mi Zhou1Junrui Guo2Danyang Chen3Cong Xing4Song Liu5Hongjiang Yang6Hongpeng Ma7Qi Zhang8Jianhai Yang9Shiqing Feng10Guangzhi Ning11International Science and Technology Cooperation Base of Spinal Cord Injury, Tianjin Key Laboratory of Spine and Spinal Cord Injury, Department of Orthopedics, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin, 300052, ChinaInternational Science and Technology Cooperation Base of Spinal Cord Injury, Tianjin Key Laboratory of Spine and Spinal Cord Injury, Department of Orthopedics, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin, 300052, ChinaInternational Science and Technology Cooperation Base of Spinal Cord Injury, Tianjin Key Laboratory of Spine and Spinal Cord Injury, Department of Orthopedics, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin, 300052, ChinaSchool of Materials Science and Engineering Tianjin Key Laboratory of Composite and Functional Materials, Tianjin University, Tianjin, 300350, ChinaInternational Science and Technology Cooperation Base of Spinal Cord Injury, Tianjin Key Laboratory of Spine and Spinal Cord Injury, Department of Orthopedics, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin, 300052, ChinaInternational Science and Technology Cooperation Base of Spinal Cord Injury, Tianjin Key Laboratory of Spine and Spinal Cord Injury, Department of Orthopedics, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin, 300052, ChinaInternational Science and Technology Cooperation Base of Spinal Cord Injury, Tianjin Key Laboratory of Spine and Spinal Cord Injury, Department of Orthopedics, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin, 300052, ChinaInternational Science and Technology Cooperation Base of Spinal Cord Injury, Tianjin Key Laboratory of Spine and Spinal Cord Injury, Department of Orthopedics, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin, 300052, ChinaInternational Science and Technology Cooperation Base of Spinal Cord Injury, Tianjin Key Laboratory of Spine and Spinal Cord Injury, Department of Orthopedics, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin, 300052, ChinaSchool of Materials Science and Engineering Tianjin Key Laboratory of Composite and Functional Materials, Tianjin University, Tianjin, 300350, China; Corresponding author.International Science and Technology Cooperation Base of Spinal Cord Injury, Tianjin Key Laboratory of Spine and Spinal Cord Injury, Department of Orthopedics, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin, 300052, China; Department of Orthopedics, Qilu Hospital of Shandong University, Shandong University Centre for Orthopedics, Advanced Medical Research Institute, Shandong University, Jinan, Shandong Province, China; Orthopedic Research Center of Shandong University & Advanced Medical Research Institute, Cheeloo College of Medicine, Shandong University, Jinan, Shandong Province, China; Corresponding author. International Science and Technology Cooperation Base of Spinal Cord Injury, Tianjin Key Laboratory of Spine and Spinal Cord Injury, Department of Orthopedics, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin, 300052, China.International Science and Technology Cooperation Base of Spinal Cord Injury, Tianjin Key Laboratory of Spine and Spinal Cord Injury, Department of Orthopedics, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin, 300052, China; Corresponding author.Spinal cord injury (SCI) is a devastating condition of the central nervous system, characterized by disrupted regulation of the immune microenvironment and the loss of electrical signaling, which poses significant challenges to repair. Neural stem cells (NSCs) have the potential to promote functional recovery after SCI; however, their therapeutic potential is limited by poor survival, restricted proliferation, and suboptimal differentiation. Human umbilical cord-derived mesenchymal stem cells (hUCMSCs) possess powerful paracrine and immunomodulatory properties, providing a supportive niche that improves the engraftment and function of NSCs. Recently, piezoelectric materials have attracted increasing attention for their ability to convert mechanical energy into electrical signals, thus providing a noninvasive, wireless alternative to traditional electrode-based therapies for neural regeneration. In this study, we investigated the synergistic effects of NSCs and hUCMSCs, focusing on how hUCMSCs direct NSC differentiation and the mechanisms underlying this action. We also introduce an ultrasound-driven wireless piezoelectric hydrogel, which generates electrical signals through the piezoelectric effect. In vitro, wireless electrical stimulation activated primary cortical neurons, stimulated axonal growth, and promoted neuronal plasticity through the Piezo1 channel and downstream CREB/CAMKII signaling pathways. In a rat SCI model, wireless piezoelectric hydrogel synergized with cotransplanting NSCs–hUCMSCs and modulated the immune microenvironment during the acute phase, thereby restructuring scar cavities during the chronic phase, suppressing scar formation, accelerating neurogenesis, and facilitating axonal regeneration. These results emphasize the potential of synergizing stem cell therapies with wireless piezoelectric stimulation as a promising strategy for SCI repair, providing novel insights into the clinical translation of regenerative treatments.http://www.sciencedirect.com/science/article/pii/S2590006425003655Spinal cord injuryPiezoelectric nanogeneratorWireless electrical stimulationUltrasound |
| spellingShingle | Hao Zhong Mi Zhou Junrui Guo Danyang Chen Cong Xing Song Liu Hongjiang Yang Hongpeng Ma Qi Zhang Jianhai Yang Shiqing Feng Guangzhi Ning Ultrasound-driven wireless piezoelectric hydrogel synergizes with cotransplantation of NSCs–hUCMSCs for structural and functional recovery in spinal cord injury Materials Today Bio Spinal cord injury Piezoelectric nanogenerator Wireless electrical stimulation Ultrasound |
| title | Ultrasound-driven wireless piezoelectric hydrogel synergizes with cotransplantation of NSCs–hUCMSCs for structural and functional recovery in spinal cord injury |
| title_full | Ultrasound-driven wireless piezoelectric hydrogel synergizes with cotransplantation of NSCs–hUCMSCs for structural and functional recovery in spinal cord injury |
| title_fullStr | Ultrasound-driven wireless piezoelectric hydrogel synergizes with cotransplantation of NSCs–hUCMSCs for structural and functional recovery in spinal cord injury |
| title_full_unstemmed | Ultrasound-driven wireless piezoelectric hydrogel synergizes with cotransplantation of NSCs–hUCMSCs for structural and functional recovery in spinal cord injury |
| title_short | Ultrasound-driven wireless piezoelectric hydrogel synergizes with cotransplantation of NSCs–hUCMSCs for structural and functional recovery in spinal cord injury |
| title_sort | ultrasound driven wireless piezoelectric hydrogel synergizes with cotransplantation of nscs hucmscs for structural and functional recovery in spinal cord injury |
| topic | Spinal cord injury Piezoelectric nanogenerator Wireless electrical stimulation Ultrasound |
| url | http://www.sciencedirect.com/science/article/pii/S2590006425003655 |
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