3D Bioprinting of Multifunctional Dynamic Nanocomposite Bioinks Incorporating Cu-Doped Mesoporous Bioactive Glass Nanoparticles for Bone Tissue Engineering

Bioprinting has seen significant progress in recent years for the fabrication of bionic tissues with high complexity. However, it remains challenging to develop cell-laden bioinks exhibiting superior physiochemical properties and bio-functionality. In this study, a multifunctional nanocomposite bioink is developed based on amine-functionalized copper (Cu)-doped mesoporous bioactive glass nanoparticles (ACuMBGNs) and a hydrogel formulation relying on dynamic covalent chemistry composed of alginate dialdehyde (oxidized alginate) and gelatin, with favorable rheological properties, improved shape fidelity, and structural stability for extrusion-based bioprinting. The reversible dynamic microenvironment in combination with the impact of cell-adhesive ligands introduced by aminated particles enables the rapid spreading (within 3 days) and high survival (>90%) of embedded human osteosarcoma cells and immortalized mouse bone marrow-derived stroma cells. Osteogenic differentiation of primary mouse bone marrow stromal stem cells (BMSCs) and angiogenesis are promoted in the bioprinted alginate dialdehyde-gelatin (ADA-GEL or AG)-ACuMBGN scaffolds without additional growth factors in vitro, which is likely due to ion stimulation from the incorporated nanoparticles and possibly due to cell mechanosensing in the dynamic matrix. In conclusion, it is envisioned that these nanocomposite bioinks can serve as promising platforms for bioprinting complex 3D matrix environments providing superior physiochemical and biological performance for bone tissue engineering.

Automated summary

Bioprinting has made significant progress in recent years in the fabrication of complex bionic tissues. However, developing cell-laden bioinks with superior physiochemical properties and bio-functionality remains challenging. In this study, a multifunctional nanocomposite bioink was developed using amine-functionalized copper-doped mesoporous bioactive glass nanoparticles and a hydrogel formulation based on dynamic covalent chemistry. This bioink showed favorable rheological properties, improved shape fidelity, and structural stability for extrusion-based bioprinting. The introduction of aminated particles and the reversible dynamic microenvironment enabled rapid spreading and high survival of embedded cells. The bioprinted scaffolds promoted osteogenic differentiation and angiogenesis of cells without additional growth factors in vitro. These nanocomposite bioinks have great potential for bioprinting complex 3D environments in bone tissue engineering.