Most drug candidates and therapeutic strategies advance to preclinical testing but ultimately fail to achieve clinical approval. A major contributor to this high failure rate is the reliance on conventional 2D monolayer cell cultures, which inadequately recapitulate the native microenvironments from which cells originate. To better predict physiological responses, there is a critical need for 3D in vitro disease models that incorporate key features of the native microenvironment and enable the study of multiscale interactions at both local and distant sites. 

Reconstructing complex tissue and organ architectures in 3D requires the precise spatial organization of living cells and functional biomaterials with high hierarchical fidelity and structural heterogeneity—capabilities that exceed those of conventional fabrication technologies. Addressing this challenge demands fundamental advances in both materials science and bioengineering.

Our approach integrates advanced manufacturing technologies, including 3D bioprinting and micro-/nanofabrication, to enable the spatiotemporal assembly of integrated biological microsystems with device-level functionality. Specifically, we aim to establish and control key biological cues that govern cell fate, thereby recapitulating critical aspects of disease progression. These 3D organotypic models are programmably fabricated through (i) precise deposition of cell-laden bioinks and (ii) guided cell self-organization through cell–cell and cell–ECM interactions, enabling dynamic (4D) modulation over time. These in vitro platforms provide powerful testbeds to (i) model disease progression and investigate underlying mechanisms from the molecular to tissue scale, and (ii) support preclinical evaluation of therapeutic strategies, drug candidates, and biomedical devices.