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

Abstract Osteomyelitis 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 (CaH 2 ), as efficient hydrogen/alkaline/calcium donors, is employed for combined osteomyelitis therapy. CaH 2 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 (Ca 2+ ) 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, CaH 2 significantly increases the permeability of the bacterial membrane, therefore increasing the entry of OH − and Ca 2+ into bacterial cells, thereby leading to significant bacterial death. After being applied to S. aureus ‐infected mouse tibia osteomyelitis, CaH 2 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.