Living Tissues by Design: The Rise of Hybrid Models in Biofabrication

Current in vitro tissue models struggle to recapitulate the structural, vascular, and mechanical complexity of human tissues, limiting their physiological relevance for disease modelling and preclinical testing. Self-organising three-dimensional cultures such as spheroids and organoids capture key aspects of cellular organisation and differentiation, but they commonly lack controlled geometry, perfusable vasculature, and reproducible mechanical microenvironments. Conversely, biofabrication strategies, such as three-dimensional (3D) bioprinting and organ-on-chip (OoC) microfluidic devices, offer spatial control, integrated perfusion, and dynamic mechanical stimulation, yet often fall short in recapitulating the full cellular diversity and self-organisation of native tissues. Notably, emerging hybrid approaches that embed self-organising biological units (e.g., organoids and spheroids) into engineered scaffolds or microfluidic platforms combine biological relevance, architectural fidelity, and functional control. Advances in bioink chemistry, sacrificial-printing vascularisation, and chip-organoid interfaces now enable perfusable, multicompartment tissues suitable for disease modelling and preclinical testing. This review highlights the most recent (2020-2025) progress in organoid vascularisation, bioprinting strategies for prevascularised constructs, and OoC integration, outlining remaining challenges and emphasising priorities for next-generation hybrid cellular and tissue models.