Microenvironment-responsive living hydrogel containing engineered probiotic for treatment of massive bone defects
Self-activating and microenvironment-responsive biomaterials for tissue regeneration would address the escalating need for bone grafting, but remain challenging. The emergence of microbial living therapeutics offers vast potential in regenerative medicine, as genetically engineered probiotics posses...
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KeAi Communications Co., Ltd.
2025-08-01
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| Series: | Bioactive Materials |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2452199X25001665 |
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| author | Haoyu Fang Yanyi Wang Li Li Xiaotong Qin Daoyu Zhu Pei Liu Qianhao Yang Youshui Gao Zhongmin Shi Xin Ma Chao Zhong Yixuan Chen |
| author_facet | Haoyu Fang Yanyi Wang Li Li Xiaotong Qin Daoyu Zhu Pei Liu Qianhao Yang Youshui Gao Zhongmin Shi Xin Ma Chao Zhong Yixuan Chen |
| author_sort | Haoyu Fang |
| collection | DOAJ |
| description | Self-activating and microenvironment-responsive biomaterials for tissue regeneration would address the escalating need for bone grafting, but remain challenging. The emergence of microbial living therapeutics offers vast potential in regenerative medicine, as genetically engineered probiotics possess efficient stimuli-responsiveness and tunable biological functions. Here, using elevated endogenous nitric oxide (NO) signals as a biological trigger in bone fracture injuries, a Living Responsive Regenerative Medicine (LRRM) strategy for in situ bone defect repair through real-time controlled release of bone morphogenetic protein-2 (BMP2) is proposed. The Escherichia coli Nissle 1917 (EcN) strain, genetically engineered to sense NO signals and correspondingly produce and secrete BMP2, was firstly encapsulated in gelatin methacryloyl (GelMA) microspheres and then embedded in a bulky hyaluronic acid methacryloyl (HAMA) hydrogel to form a living hydrogel device that circumvents immune attack and prevents bacterial leakage. In vivo multiple bone defect models demonstrated the efficacy of the living hydrogel in enhancing the maturation of bone callus, promoting neovascularization, and facilitating full-thickness bone union. Strategic incorporation of engineered probiotics and the bilayer-structured encapsulation system may emerge as an effective and microenvironment-responsive medicine approach for tissue regeneration. |
| format | Article |
| id | doaj-art-82484ddafdcd4d418e764d5a58b33d18 |
| institution | Kabale University |
| issn | 2452-199X |
| language | English |
| publishDate | 2025-08-01 |
| publisher | KeAi Communications Co., Ltd. |
| record_format | Article |
| series | Bioactive Materials |
| spelling | doaj-art-82484ddafdcd4d418e764d5a58b33d182025-08-20T03:45:15ZengKeAi Communications Co., Ltd.Bioactive Materials2452-199X2025-08-015055657010.1016/j.bioactmat.2025.04.020Microenvironment-responsive living hydrogel containing engineered probiotic for treatment of massive bone defectsHaoyu Fang0Yanyi Wang1Li Li2Xiaotong Qin3Daoyu Zhu4Pei Liu5Qianhao Yang6Youshui Gao7Zhongmin Shi8Xin Ma9Chao Zhong10Yixuan Chen11Department of Orthopedic Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, ChinaCenter for Materials Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology (SIAT), Chinese Academy of Sciences (CAS), Shenzhen, 518055, China; CAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology (SIAT), Chinese Academy of Sciences (CAS), Shenzhen, 518055, ChinaState Key Laboratory of Food Nutrition & Safety, Tianjin University of Science & Technology, Tianjin, 300457, China; Key Laboratory of Industrial Fermentation Microbiology (Ministry of Education), Tianjin University of Science & Technology, Tianjin, 300457, ChinaState Key Laboratory of Food Nutrition & Safety, Tianjin University of Science & Technology, Tianjin, 300457, China; Key Laboratory of Industrial Fermentation Microbiology (Ministry of Education), Tianjin University of Science & Technology, Tianjin, 300457, ChinaDepartment of Orthopedic Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, ChinaDepartment of Orthopedic Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, ChinaDepartment of Orthopedic Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, ChinaDepartment of Orthopedic Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, ChinaDepartment of Orthopedic Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China; Corresponding author.Department of Orthopedic Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China; Corresponding author.Center for Materials Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology (SIAT), Chinese Academy of Sciences (CAS), Shenzhen, 518055, China; CAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology (SIAT), Chinese Academy of Sciences (CAS), Shenzhen, 518055, China; Corresponding author. Center for Materials Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology (SIAT), Chinese Academy of Sciences (CAS), Shenzhen 518055, China.Department of Orthopedic Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China; Corresponding author.Self-activating and microenvironment-responsive biomaterials for tissue regeneration would address the escalating need for bone grafting, but remain challenging. The emergence of microbial living therapeutics offers vast potential in regenerative medicine, as genetically engineered probiotics possess efficient stimuli-responsiveness and tunable biological functions. Here, using elevated endogenous nitric oxide (NO) signals as a biological trigger in bone fracture injuries, a Living Responsive Regenerative Medicine (LRRM) strategy for in situ bone defect repair through real-time controlled release of bone morphogenetic protein-2 (BMP2) is proposed. The Escherichia coli Nissle 1917 (EcN) strain, genetically engineered to sense NO signals and correspondingly produce and secrete BMP2, was firstly encapsulated in gelatin methacryloyl (GelMA) microspheres and then embedded in a bulky hyaluronic acid methacryloyl (HAMA) hydrogel to form a living hydrogel device that circumvents immune attack and prevents bacterial leakage. In vivo multiple bone defect models demonstrated the efficacy of the living hydrogel in enhancing the maturation of bone callus, promoting neovascularization, and facilitating full-thickness bone union. Strategic incorporation of engineered probiotics and the bilayer-structured encapsulation system may emerge as an effective and microenvironment-responsive medicine approach for tissue regeneration.http://www.sciencedirect.com/science/article/pii/S2452199X25001665Living hydrogelBacterial engineeringSmart biomaterialSensing-reportingRegenerative medicine |
| spellingShingle | Haoyu Fang Yanyi Wang Li Li Xiaotong Qin Daoyu Zhu Pei Liu Qianhao Yang Youshui Gao Zhongmin Shi Xin Ma Chao Zhong Yixuan Chen Microenvironment-responsive living hydrogel containing engineered probiotic for treatment of massive bone defects Bioactive Materials Living hydrogel Bacterial engineering Smart biomaterial Sensing-reporting Regenerative medicine |
| title | Microenvironment-responsive living hydrogel containing engineered probiotic for treatment of massive bone defects |
| title_full | Microenvironment-responsive living hydrogel containing engineered probiotic for treatment of massive bone defects |
| title_fullStr | Microenvironment-responsive living hydrogel containing engineered probiotic for treatment of massive bone defects |
| title_full_unstemmed | Microenvironment-responsive living hydrogel containing engineered probiotic for treatment of massive bone defects |
| title_short | Microenvironment-responsive living hydrogel containing engineered probiotic for treatment of massive bone defects |
| title_sort | microenvironment responsive living hydrogel containing engineered probiotic for treatment of massive bone defects |
| topic | Living hydrogel Bacterial engineering Smart biomaterial Sensing-reporting Regenerative medicine |
| url | http://www.sciencedirect.com/science/article/pii/S2452199X25001665 |
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