A H2-bioreactor for mitochondrial rehabilitation in infected bone defects regeneration

Abstract

The repair of infected bone defects (IBDs) presents a significant clinical challenge due to recurrent infections and inflammation. Characterized by reactive oxygen species (ROS) bursts and mitochondrial dysfunction, IBDs generates to a vicious oxidation-inflammation cycle that impairs bone remodeling. To address this, we developed a double-network hydrogel scaffold composed of phenylboronic acid-modified quaternary chitosan and glycidyl methacrylated poly(vinyl alcohol) (QP-P), crosslinked via dynamic boronic ester bonds and covalent bonds, loaded with magnesium microspheres (Mg spheres) (QP-P/Mg). This double-crosslinking network confers excellent injectability and tissue adhesion while integrating potent antibacterial, ROS-scavenging, pro-angio genic, and osteogenic functions. Notably, Mg spheres enable controlled hydrolysis through a boronic ester- magnesium ion (Mg2+) complexation mechanism, providing sustained release of hydrogen (H2) and Mg2+, with H2 potently alleviating oxidative stress and restoring mitochondrial homeostasis via the Nrf2/HO-1 pathway and Mg2+ promoting vascularized bone regeneration. In a rat IBDs model, QP-P/Mg achieved sub stantial bone regeneration, with a BV/TV ratio of 45.32 % ± 8.22 % after 4 weeks, representing a 6.27-fold improvement over controls. These findings underscore the potential of this H2-releasing hydrogel scaffold with multifunctional properties to promote vascularized bone regeneration in IBDs through ROS elimination and mitochondrial rehabilitation, offering promising clinical translational opportunities for the treatment of IBDs.

Study details

Article type

Original Research

Disease / injury model

Infected bone defects (IBDs) in rats (alveolar bone defect model with S. aureus infection)

Duration

4 weeks

Dose comparison

Different concentrations of Mg spheres (1, 5, 10 mM) in the hydrogel were tested for antioxidant and osteogenic effects, showing concentration-dependent activity.

Dose-dependent effect

Yes

Outcome

Positive

Findings

The study demonstrates that a hydrogen-releasing double-network hydrogel scaffold (QP-P/Mg) significantly enhances bone regeneration in a rat model of infected bone defects by alleviating oxidative stress, restoring mitochondrial function, and promoting angiogenesis and osteogenesis. The scaffold achieved a 6.27-fold improvement in bone volume fraction (BV/TV) over controls after 4 weeks, with potent antibacterial, antioxidant, and tissue regenerative properties.