Mechanisms of Action
An overview of bioactive glass, the gallium dissolution mechanism, and the laboratory evidence underpinning OncoGlass as a dual-action bone cancer implant
· Aston University · TRL 3
Bioactive Glass
Bioactive glass is a synthetic, silica-based biomaterial first developed by Larry Hench in 1969. Unlike inert implant materials, bioactive glass is capable of forming a direct chemical bond with living bone. This property allows it to actively participate in the healing process rather than simply providing structural support, making it a widely studied material in regenerative medicine.
The most well-known formulation, 45S5 bioactive glass, consists of 45% SiO₂, 24.5% Na₂O, 24.5% CaO, and 6% P₂O₅. This specific composition enables controlled dissolution in physiological environments and the formation of a biologically active surface. 45S5 has been used clinically for decades and is approved for use in orthopaedic and dental applications, demonstrating both safety and effectiveness in bone repair.
Gallium-doped bioactive glass (GaBG) builds on this established platform by incorporating gallium oxide into the glass matrix. In this context, “doping” refers to the intentional addition of a therapeutic ion to modify the material’s biological function. Gallium was selected due to its known anticancer properties and its ability to interfere with iron-dependent cellular processes, making it a promising candidate for localised cancer treatment.
Properties and Mechanisms of Dissolution
When bioactive glass is implanted, it begins to dissolve in biological fluid and releases ionic products through a sequence of surface reactions. This process starts with ion exchange at the glass surface and progresses through silica gel layer formation, calcium phosphate precipitation, and hydroxy-carbonate apatite crystallisation. The end result is a strong interfacial bond between the material and host bone.
These ionic dissolution products do more than change the material surface. Calcium, phosphate, and silicon ions are known to stimulate osteoblast activity and support new bone formation. This regenerative mechanism underpins the clinical use of bioactive glass in bone repair and is a key reason it provides a strong foundation for OncoGlass.
Ion Exchange
Na⁺ and Ca²⁺ exchange with H⁺ from body fluid at the glass surface
Silica Gel Layer
Si–OH groups condense to form a hydrated silica layer
Ca–P Layer
Ca²⁺ and PO₄³⁻ migrate and form an amorphous calcium phosphate layer
HCA Crystallisation
The Ca–P layer crystallises into hydroxy-carbonate apatite, bonding to host bone
Bone Formation
Ionic products stimulate osteoblast proliferation and new bone matrix deposition
In gallium-doped bioactive glass, gallium ions are released alongside the standard dissolution products. This adds a second therapeutic function to the material. Gallium mimics iron in biological systems, is taken up by cancer cells through transferrin receptors, and disrupts iron-dependent metabolic processes. This mechanism enables selective cancer cell death while largely sparing healthy tissue
Gallium Anticancer Mechanism
OncoGlass dissolves at the implant site, releasing Ga³⁺ ions locally into the surrounding tissue alongside standard dissolution products.
Ga³⁺ has a similar ionic radius to Fe³⁺. Transferrin receptors on cell surfaces cannot distinguish between them, and actively transport gallium into the cell.
Cancer cells overexpress transferrin receptors to fuel rapid proliferation, resulting in substantially higher gallium uptake compared to healthy tissue.
Internalised gallium disrupts ribonucleotide reductase and other iron-dependent enzymes critical for DNA synthesis, causing cancer cell death.
Healthy cells express far fewer transferrin receptors and are largely unaffected at concentrations lethal to cancer cells.
In Vitro Study Results
The in vitro performance of gallium-doped bioactive glass has been evaluated using PC3 and SK-RC-46 cancer cell lines, with human osteoblasts, or HOBs, included as a healthy control. A range of GaBG concentrations was tested to assess cytotoxicity, selectivity, and cell response. These results are reported in Hanaei et al., Biomedical Materials (2024).
The study showed that GaBG produced significant cytotoxicity against both cancer cell lines at concentrations that preserved HOB viability. This finding supports the proposed selectivity mechanism in vitro and provides early evidence that the material can combine anticancer activity with compatibility toward healthy bone-forming cells.
Important: All data are from in vitro laboratory studies. OncoGlass is a pre-clinical research material at TRL 3. These findings do not constitute clinical evidence of efficacy or safety in humans. Further pre-clinical and clinical evaluation is required before any clinical application.
References
- Hench, L. L. (1969). Development of bioactive glass for bone bonding applications.
- Hanaei, S. et al. (2024). Gallium-doped bioactive glass for selective anticancer activity. Biomedical Materials.