K+-H+ coupling strategy for immune regulation and bone defect repair
Ion homeostasis is crucial for maintaining cell function. Potassium ion (K+) is one of the most important cations in the human body, and it plays key role in maintaining biological activities and cellular functions, including the intricate balance of ion homeostasis that underpins both physiological...
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Elsevier
2025-06-01
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2590006425003035 |
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| author | Lintao Hu Ke Yang Yiyu Chen Haoli Wang Zezhou Fu Lejian Jiang Jiachen Xu Hongsen Tian Yiwei Zhu Zhanqiu Dai Yijun Li Xianhua Chen Xianfeng Lin Pengfei Chen Chenhui Gu Shunwu Fan |
| author_facet | Lintao Hu Ke Yang Yiyu Chen Haoli Wang Zezhou Fu Lejian Jiang Jiachen Xu Hongsen Tian Yiwei Zhu Zhanqiu Dai Yijun Li Xianhua Chen Xianfeng Lin Pengfei Chen Chenhui Gu Shunwu Fan |
| author_sort | Lintao Hu |
| collection | DOAJ |
| description | Ion homeostasis is crucial for maintaining cell function. Potassium ion (K+) is one of the most important cations in the human body, and it plays key role in maintaining biological activities and cellular functions, including the intricate balance of ion homeostasis that underpins both physiological and pathological processes. This study explored a novel role of K+ ions in regulating immune cell function and promoting tissue repair, especially in macrophage-mediated environments after severe tissue injury. We designed and synthesized a platelet-liposome vesicles loaded KHCO3 (KHCO3@PLV) that precisely delivered potassium bicarbonate to the site of injury extracellular after intravenous injection; then, precise ultrasound-triggered K+ release regulated extracellular K+ concentrations in the local macrophage environment. These effects collectively validate the K+-H+ coupling strategy - a novel mechanism whereby extracellular K+ elevation induces intracellular pH modulation, subsequently activating the AMPK/Nrf2 axis to reprogram macrophage metabolism and facilitating tissue regeneration through resolution of chronic inflammation. The main conclusion of the study is that an elevated extracellular K+ environment, which is an innovative treatment, is a potentially effective strategy for regulating immune responses and promoting repair after severe tissue injury. |
| format | Article |
| id | doaj-art-426dc32ea04a47feb50786f6cc6932c6 |
| institution | OA Journals |
| issn | 2590-0064 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Materials Today Bio |
| spelling | doaj-art-426dc32ea04a47feb50786f6cc6932c62025-08-20T02:12:15ZengElsevierMaterials Today Bio2590-00642025-06-013210174410.1016/j.mtbio.2025.101744K+-H+ coupling strategy for immune regulation and bone defect repairLintao Hu0Ke Yang1Yiyu Chen2Haoli Wang3Zezhou Fu4Lejian Jiang5Jiachen Xu6Hongsen Tian7Yiwei Zhu8Zhanqiu Dai9Yijun Li10Xianhua Chen11Xianfeng Lin12Pengfei Chen13Chenhui Gu14Shunwu Fan15Department of Orthopaedics Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310016, China; Key Laboratory of Mechanism Research and Precision Repair of Orthopaedics Trauma and Aging Diseases of Zhejiang Province, Hangzhou, China, Hangzhou, Zhejiang 310016, ChinaDepartment of Orthopaedics Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310016, China; Key Laboratory of Mechanism Research and Precision Repair of Orthopaedics Trauma and Aging Diseases of Zhejiang Province, Hangzhou, China, Hangzhou, Zhejiang 310016, ChinaDepartment of Orthopaedics Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310016, China; Key Laboratory of Mechanism Research and Precision Repair of Orthopaedics Trauma and Aging Diseases of Zhejiang Province, Hangzhou, China, Hangzhou, Zhejiang 310016, ChinaDepartment of Orthopaedics Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310016, China; Key Laboratory of Mechanism Research and Precision Repair of Orthopaedics Trauma and Aging Diseases of Zhejiang Province, Hangzhou, China, Hangzhou, Zhejiang 310016, ChinaDepartment of Orthopaedics Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310016, China; Key Laboratory of Mechanism Research and Precision Repair of Orthopaedics Trauma and Aging Diseases of Zhejiang Province, Hangzhou, China, Hangzhou, Zhejiang 310016, ChinaDepartment of Orthopaedics Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310016, China; Key Laboratory of Mechanism Research and Precision Repair of Orthopaedics Trauma and Aging Diseases of Zhejiang Province, Hangzhou, China, Hangzhou, Zhejiang 310016, China; Department of Orthopaedics Surgery, The Fourth Affiliated Hospital of Zhejiang University School of Medicine, Yiwu, Zhejiang 322000, ChinaDepartment of Orthopaedics Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310016, China; Key Laboratory of Mechanism Research and Precision Repair of Orthopaedics Trauma and Aging Diseases of Zhejiang Province, Hangzhou, China, Hangzhou, Zhejiang 310016, China; School of Basic Medical Sciences and Forensic Medicine, Hangzhou Medical College, Hangzhou, Zhejiang 310000, ChinaDepartment of Orthopaedics Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310016, China; Key Laboratory of Mechanism Research and Precision Repair of Orthopaedics Trauma and Aging Diseases of Zhejiang Province, Hangzhou, China, Hangzhou, Zhejiang 310016, ChinaDepartment of Orthopaedics Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310016, China; Key Laboratory of Mechanism Research and Precision Repair of Orthopaedics Trauma and Aging Diseases of Zhejiang Province, Hangzhou, China, Hangzhou, Zhejiang 310016, ChinaDepartment of Orthopaedics Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310016, China; Key Laboratory of Mechanism Research and Precision Repair of Orthopaedics Trauma and Aging Diseases of Zhejiang Province, Hangzhou, China, Hangzhou, Zhejiang 310016, China; Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325035, ChinaDepartment of Orthopaedics Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310016, China; Key Laboratory of Mechanism Research and Precision Repair of Orthopaedics Trauma and Aging Diseases of Zhejiang Province, Hangzhou, China, Hangzhou, Zhejiang 310016, ChinaZhejiang Institute of Medical Device Supervition and Testing, Hangzhou, Zhejiang 310016, ChinaDepartment of Orthopaedics Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310016, China; Key Laboratory of Mechanism Research and Precision Repair of Orthopaedics Trauma and Aging Diseases of Zhejiang Province, Hangzhou, China, Hangzhou, Zhejiang 310016, China; Cixi Institute of Biomedicine, Wenzhou Medical University, Ningbo, Zhejiang 315000, China; Corresponding author. Department of Orthopaedics Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310016, China.Department of Orthopaedics Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310016, China; Key Laboratory of Mechanism Research and Precision Repair of Orthopaedics Trauma and Aging Diseases of Zhejiang Province, Hangzhou, China, Hangzhou, Zhejiang 310016, China; Corresponding author. Department of Orthopaedics Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310016, China.Department of Orthopaedics Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310016, China; Key Laboratory of Mechanism Research and Precision Repair of Orthopaedics Trauma and Aging Diseases of Zhejiang Province, Hangzhou, China, Hangzhou, Zhejiang 310016, China; Corresponding author. Department of Orthopaedics Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310016, China.Department of Orthopaedics Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310016, China; Key Laboratory of Mechanism Research and Precision Repair of Orthopaedics Trauma and Aging Diseases of Zhejiang Province, Hangzhou, China, Hangzhou, Zhejiang 310016, China; Corresponding author. Department of Orthopaedics Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310016, China.Ion homeostasis is crucial for maintaining cell function. Potassium ion (K+) is one of the most important cations in the human body, and it plays key role in maintaining biological activities and cellular functions, including the intricate balance of ion homeostasis that underpins both physiological and pathological processes. This study explored a novel role of K+ ions in regulating immune cell function and promoting tissue repair, especially in macrophage-mediated environments after severe tissue injury. We designed and synthesized a platelet-liposome vesicles loaded KHCO3 (KHCO3@PLV) that precisely delivered potassium bicarbonate to the site of injury extracellular after intravenous injection; then, precise ultrasound-triggered K+ release regulated extracellular K+ concentrations in the local macrophage environment. These effects collectively validate the K+-H+ coupling strategy - a novel mechanism whereby extracellular K+ elevation induces intracellular pH modulation, subsequently activating the AMPK/Nrf2 axis to reprogram macrophage metabolism and facilitating tissue regeneration through resolution of chronic inflammation. The main conclusion of the study is that an elevated extracellular K+ environment, which is an innovative treatment, is a potentially effective strategy for regulating immune responses and promoting repair after severe tissue injury.http://www.sciencedirect.com/science/article/pii/S2590006425003035Ion homeostasisPotassiumIntracellular pHImmune regulationTissue repair |
| spellingShingle | Lintao Hu Ke Yang Yiyu Chen Haoli Wang Zezhou Fu Lejian Jiang Jiachen Xu Hongsen Tian Yiwei Zhu Zhanqiu Dai Yijun Li Xianhua Chen Xianfeng Lin Pengfei Chen Chenhui Gu Shunwu Fan K+-H+ coupling strategy for immune regulation and bone defect repair Materials Today Bio Ion homeostasis Potassium Intracellular pH Immune regulation Tissue repair |
| title | K+-H+ coupling strategy for immune regulation and bone defect repair |
| title_full | K+-H+ coupling strategy for immune regulation and bone defect repair |
| title_fullStr | K+-H+ coupling strategy for immune regulation and bone defect repair |
| title_full_unstemmed | K+-H+ coupling strategy for immune regulation and bone defect repair |
| title_short | K+-H+ coupling strategy for immune regulation and bone defect repair |
| title_sort | k h coupling strategy for immune regulation and bone defect repair |
| topic | Ion homeostasis Potassium Intracellular pH Immune regulation Tissue repair |
| url | http://www.sciencedirect.com/science/article/pii/S2590006425003035 |
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