Bioactive Calcium Hydride‐Driving “Triple” Hydrogen/Alkaline/Calcium Therapy for Efficient Treatment of Osteomyelitis

Author:

Chen Lin12,Cheng Shuning3,Lu Shunyi4,Gao Xiang1,Gong Fei3,Shi Junwu2,Han Zhihui3,Wang Yuanjie3,Yang Xiaoyuan3,Zhou Xiaozhong1,Cheng Liang35ORCID

Affiliation:

1. Department of Orthopedics The Second Affiliated Hospital of Soochow University Suzhou 215000 China

2. Department of Orthopedics Wenzhou Central Hospital Wenzhou 325027 China

3. Institute of Functional Nano & Soft Materials (FUNSOM) Jiangsu Key Laboratory for Carbon‐Based Functional Materials & Devices Soochow University Suzhou 215123 China

4. Department of Orthopaedic Surgery The First Affiliated Hospital of Soochow University Suzhou 215006 China

5. Macao Institute of Materials Science and Engineering Macau University of Science and Technology Taipa Macau SAR 999078 China

Abstract

AbstractOsteomyelitis with high mortality and disability rates is a common clinical disease caused by a bacterial infection that is difficult to cure. Considering the stubborn nature and depth of tissue infection, rapid and effective treatments for osteomyelitis remain an enormous challenge. Calcium hydride (CaH2), as efficient hydrogen/alkaline/calcium donors, is employed for combined osteomyelitis therapy. CaH2 reacts with water to sufficiently generate a strong alkali environment with hydroxide anions (OH) to inhibit bacterial proliferation and induce bacterial death. The released calcium ions (Ca2+) induce calcium overload to kill bacteria first and then serves as calcium source to promote new bone formation. Another byproduct, hydrogen enhances the bacterial membrane permeability and scavenges excess reactive oxygen species (ROS). After incubation with bacteria, CaH2 significantly increases the permeability of the bacterial membrane, therefore increasing the entry of OH and Ca2+ into bacterial cells, thereby leading to significant bacterial death. After being applied to S. aureus‐infected mouse tibia osteomyelitis, CaH2 materials efficiently kill bacteria, relieve local inflammation, and promote new bone formation in a short time. Overall, bioactive metal hydride‐associated “triple” hydrogen/alkaline/calcium therapy provides a new idea for the treatment of deep‐site bacterial infection, which is beneficial for relieving the pressure caused by antibiotic‐resistant bacteria.

Funder

National Natural Science Foundation of China

Collaborative Innovation Center of Suzhou Nano Science and Technology

Higher Education Discipline Innovation Project

China Postdoctoral Science Foundation

Publisher

Wiley

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