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In this study, a single\u2010component self\u2010assembling hydrogel is developed using the recombinant protein CsgA, and its successful application for spinal cord injury repair is demonstrated. Gelation is achieved by the physical entanglement of CsgA nanofibrils, resulting in a self\u2010supporting hydrogel at low concentrations (\u22655\u00a0mg mL<jats:sup>\u22121<\/jats:sup>). By leveraging the programmability of the CsgA gene sequence, the bioactive hydrogel is enhanced by fusing functional peptide GHK. GHK is recognized for its anti\u2010inflammatory, antioxidant, and neurotrophic factor\u2010stimulating properties, making it a valuable addition to the hydrogel for spinal cord injury repair applications. In vitro experiments demonstrate that the CsgA\u2010GHK hydrogel can modulate microglial M2 polarization, promote neuronal differentiation of neural stem cells, and inhibit astrocyte differentiation. Additionally, the hydrogel shows efficacy in alleviating inflammation and promotes neuronal regeneration at the injury site, leading to significant functional recovery in a rat model with compression injury spinal cord cavity. These findings lay the groundwork for developing a modular design platform for recombinant CsgA protein hydrogels in tissue repair applications.<\/jats:p>","DOI":"10.1002\/advs.202405054","type":"journal-article","created":{"date-parts":[[2025,1,10]],"date-time":"2025-01-10T13:29:39Z","timestamp":1736515779000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Genetically Programmed Single\u2010Component Protein Hydrogel for Spinal Cord Injury Repair"],"prefix":"10.1002","volume":"12","author":[{"given":"Yi","family":"Wei","sequence":"first","affiliation":[{"name":"Wenzhou Institute University of Chinese Academy of Sciences  Wenzhou Zhejiang 325001 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolin","family":"Zhou","sequence":"additional","affiliation":[{"name":"Wenzhou Institute University of Chinese Academy of Sciences  Wenzhou Zhejiang 325001 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenhua","family":"Li","sequence":"additional","affiliation":[{"name":"Wenzhou Institute University of Chinese Academy of Sciences  Wenzhou Zhejiang 325001 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Liu","sequence":"additional","affiliation":[{"name":"Wenzhou Institute University of Chinese Academy of Sciences  Wenzhou Zhejiang 325001 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han","family":"Ding","sequence":"additional","affiliation":[{"name":"Wenzhou Institute University of Chinese Academy of Sciences  Wenzhou Zhejiang 325001 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunlong","family":"Zhou","sequence":"additional","affiliation":[{"name":"Wenzhou Institute University of Chinese Academy of Sciences  Wenzhou Zhejiang 325001 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruo\u2010feng","family":"Yin","sequence":"additional","affiliation":[{"name":"China\u2010Japan Union Hospital Jilin University  Changchun Jilin 130031 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2819-4172","authenticated-orcid":false,"given":"Lifei","family":"Zheng","sequence":"additional","affiliation":[{"name":"Wenzhou Institute University of Chinese Academy of Sciences  Wenzhou Zhejiang 325001 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,1,10]]},"reference":[{"key":"e_1_2_8_1_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2017.18"},{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41413-022-00199-9"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3053"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aav5086"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-022-00562-y"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-022-01010-1"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-020-00770-9"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(14)70144-9"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.4103\/1673-5374.375304"},{"key":"e_1_2_8_10_1","first-page":"16","volume":"9","author":"Wang Y.","year":"2022","journal-title":"Mil. 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