2. Academic Validation
  3. K+-H+ coupling strategy for immune regulation and bone defect repair

K+-H+ coupling strategy for immune regulation and bone defect repair

  • Mater Today Bio. 2025 Apr 9:32:101744. doi: 10.1016/j.mtbio.2025.101744.
Lintao Hu 1 2,  Ke Yang 1 2,  Yiyu Chen 1 2,  Haoli Wang 1 2,  Zezhou Fu 1 2,  Lejian Jiang 1 2 3,  Jiachen Xu 1 2 4,  Hongsen Tian 1 2,  Yiwei Zhu 1 2,  Zhanqiu Dai 1 2 5,  Yijun Li 1 2,  Xianhua Chen 6,  Xianfeng Lin 1 2 7,  Pengfei Chen 1 2,  Chenhui Gu 1 2,  Shunwu Fan 1 2
Affiliations

Affiliations

  • 1 Department of Orthopaedics Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310016, China.
  • 2 Key Laboratory of Mechanism Research and Precision Repair of Orthopaedics Trauma and Aging Diseases of Zhejiang Province, Hangzhou, China, Hangzhou, Zhejiang 310016, China.
  • 3 Department of Orthopaedics Surgery, The Fourth Affiliated Hospital of Zhejiang University School of Medicine, Yiwu, Zhejiang 322000, China.
  • 4 School of Basic Medical Sciences and Forensic Medicine, Hangzhou Medical College, Hangzhou, Zhejiang 310000, China.
  • 5 Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
  • 6 Zhejiang Institute of Medical Device Supervition and Testing, Hangzhou, Zhejiang 310016, China.
  • 7 Cixi Institute of Biomedicine, Wenzhou Medical University, Ningbo, Zhejiang 315000, China.
PMID: 40275952 DOI: 10.1016/j.mtbio.2025.101744
Abstract

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.

Keywords

Immune regulation; Intracellular pH; Ion homeostasis; Potassium; Tissue repair.

Figures
Products