3D triply periodic minimal surface gyroid hydrogel scaffolds for soft tissue engineering

Abstract Engineering functional soft tissue constructs remains difficult because scaffolds must meet the mechanical, physicochemical, and biological requirements simultaneously. Here, we present a cell-laden hydrogel gyroid scaffold designed to support vascularisation, long-term multicellular culture, and implantation for the development of 3D tissue constructs. The scaffold is structurally optimised to balance nutrient transport and mechanical stability, and is fabricated with high fidelity by mitigating cell-induced light scattering. The gyroid architecture supports the formation of dense microvascular networks throughout the 3D construct, and its curved Gaussian curvature promotes endothelial self-assembly. The scaffold also enables high-density co-culture of HepG2 cells and HUVECs without active perfusion, resulting in a vascularised 3D liver tumour model with enhanced tissue-specific function. Upon subcutaneous implantation in mice, the constructs show enhanced neovascularisation and facilitate tumour formation. These findings identify the gyroid scaffold as a biologically favourable architecture for generating bulk vascularised constructs, with potential applications in disease modelling, drug screening and regenerative medicine.