Innovative implant delivers sustained hydrogen therapy

Diabetes, a chronic metabolic disease marked by high blood sugar, is linked to complications that hinder tissue repair and immunity. Diabetic patients face significantly higher orthopedic implant failure rates, mainly due to hyperglycemia-induced inflammation, oxidative stress, neuropathy, and vasculopathy.

Molecular hydrogen (H₂) has anti-inflammatory and antioxidant potential, but current delivery methods lack localized, sustained release and implant integration. Ammonia borane (AB), though high in hydrogen content, faces challenges such as uncontrolled hydrolysis causing toxic byproducts and gas embolism risk, and cytotoxicity when reacting with hydrogen peroxide (H₂O₂) in inflamed tissues.

In a study published in Advanced Materials, a team led by Prof. WANG Guocheng from the Shenzhen Institute of Advanced Technology (SIAT) of the Chinese Academy of Sciences, Prof. KONG Liang from Air Force Medical University, and Prof. ZHAO Xiaobing from Changzhou University, developed an innovative H₂ delivery technology and H₂-releasing titanium implant, allowing for controlled and sustained H₂ release to facilitate bone repair in diabetic conditions.

Researchers developed a novel nanoconfinement strategy. They first engineered a hybrid micro/nano-structured, oxygen vacancy-rich titanate nanocrystal coating (HyPT) on the surface of titanium alloy implant via plasma spraying and hydrothermal treatment. They then constructed the AB@HyPT-Mg composite coating by sequentially loading magnesium ion (Mg²⁺) and AB.

The innovation lies in the mechanism whereby AB molecules are anchored at one end within the titanate interlayers. This unique confinement effectively restricts AB release, allowing only water molecules to penetrate for gradual hydrolysis. As a result, sustained and controllable H₂ release is achieved over a period of up to 11 days, with the prevention of AB molecules and their potential cytotoxic interaction with H₂O₂.

In vitro research demonstrated that the coating effectively scavenged reactive oxygen species, upregulated antioxidant gene expression, and significantly promoted nerve regeneration, vascularization, and M2 macrophage polarization under high-glucose conditions. Notably, the sustained release of H₂ synergized with Mg²⁺ ions, enhancing the regeneration of neuro-vascular networks and promoting the osteogenic differentiation of bone marrow mesenchymal stem cells.

In a diabetic rabbit bone defect model, AB@HyPT-Mg implants exhibited superior bone regeneration, accompanied by robust neural and vascular regeneration. The technology also showed promising efficacy and biosafety in normoglycemic models, underscoring its broad therapeutic potential across diverse physiological conditions.

This study repurposes the nanoconfinement strategy to controlled and sustained hydrolysis within a biomedical implant delivery system, addressing the key limitations of conventional H₂ therapy. By integrating the therapeutic effects of H₂ and Mg²⁺, it elucidates their synergistic mechanism in promoting "innervated-vascularized bone regeneration."