Copper-Enhanced Bioactive Glasses for Tissue Engineering

Copper-enhanced bioactive glasses are silica-based biomaterials doped with therapeutic levels of copper ions to harness their antimicrobial, pro-angiogenic and immunomodulatory properties. Synthesised via sol-gel or melt-derived routes, these glasses can be engineered as bulk scaffolds, nanoparticles or surface coatings with tailored compositions and mesoporous architectures for controlled ion release. In physiological environments, copper-doped glasses rapidly precipitate a hydroxyapatite-like layer, supporting osteogenic differentiation of stem cells and encouraging vascular invasion through endothelial cell stimulation. Concurrently, copper ions direct macrophage polarisation toward anti-inflammatory phenotypes, reducing chronic inflammation and promoting tissue repair. Advances in additive manufacturing and post-functionalisation enable precise control over scaffold porosity, mechanical strength and ion delivery kinetics. By combining antimicrobial action against drug-resistant pathogens with enhancement of angiogenesis and bone regeneration, copper-enhanced bioactive glasses address the global challenge of infected bone defects, osteochondral repair and implant-associated complications.

Research from Nature Portfolio

Recent studies have interrogated the concentration-dependent effects of copper ions on macrophage polarisation within pro-inflammatory environments. One investigation demonstrated that low micromolar levels of copper promote anti-inflammatory M2 phenotypes, while higher concentrations induce pro-inflammatory markers, highlighting the need to fine-tune ion release profiles in bioactive glass systems. The work further revealed synergistic interactions between copper and magnesium ions in attenuating M1 responses under mild inflammatory stimuli, offering insights for the design of immunomodulatory glass compositions that support tissue healing.

Research from all publishers

Approaches to synthesise copper-doped mesoporous bioactive glass nanoparticles have utilised chelating post-modification strategies to achieve high copper loadings without compromising particle homogeneity or porosity. These nanoparticles rapidly induce apatite deposition in simulated body fluids and exhibit potent, dose-dependent bactericidal activity against methicillin-resistant Staphylococcus aureus, while maintaining preosteoblast viability and enabling intracellular delivery for combating bone infections.

A comprehensive review of copper-based biomaterials has underscored their dual antibacterial and osteogenic functions, detailing copper’s disruption of bacterial membranes, generation of reactive oxygen species and activation of host osteogenic signalling. Design guidelines emphasise the optimisation of copper concentration and delivery kinetics to balance antimicrobial efficacy with cytocompatibility.

Earlier work on copper-incorporated bioactive glass-ceramics demonstrated that copper release from 3D-printed scaffolds enhances chondrocyte proliferation, shifts macrophages toward anti-inflammatory phenotypes and promotes osteochondral interface regeneration, mediated by hypoxia-inducible factor signalling.

Copper-Enhanced Bioactive Glasses for Tissue Engineering publication trend

The graph below shows the total number of articles in copper-enhanced bioactive glasses for tissue engineering across all publications each year (not limited to Nature Index journals).

Technical terms

Bioactive glass: A silica-based amorphous material that forms a hydroxyapatite-like layer in physiological fluids and bonds to bone.

Ionic doping: Incorporation of therapeutic ions (e.g., Cu²⁺) into a glass network to confer bioactive functionalities.

Osteoimmunomodulation: The modulation of immune cell behaviour to support bone healing and prevent chronic inflammation.

Angiogenesis: The process of new blood vessel formation essential for nutrient delivery in regenerating tissues.

Scaffold: A three-dimensional framework that supports cell attachment, proliferation and differentiation in tissue engineering.

References

1. Copper-incorporated bioactive glass-ceramics inducing anti-inflammatory phenotype and regeneration of cartilage/bone interface. Theranostics (2019).
2. Bioactive Copper-Doped Glass Scaffolds Can Stimulate Endothelial Cells in Co-Culture in Combination with Mesenchymal Stem Cells. PLOS ONE (2014).
3. Evaluation of the immunomodulatory effects of cobalt, copper and magnesium ions in a pro inflammatory environment. Scientific Reports (2021).
4. Advances in Copper-Based Biomaterials With Antibacterial and Osteogenic Properties for Bone Tissue Engineering. Frontiers in Bioengineering and Biotechnology (2022).
5. Facile post modification synthesis of copper-doped mesoporous bioactive glass with high antibacterial performance to fight bone infection. Biomaterials Advances (2022).
6. 3D Scaffolds of Polycaprolactone/Copper-Doped Bioactive Glass: Architecture Engineering with Additive Manufacturing and Cellular Assessments in a Coculture of Bone Marrow Stem Cells and Endothelial Cells. ACS Biomaterials Science & Engineering (2019).