3D stamp-integrated open-top microfluidic organ-on-a-chip for high-fidelity and functional reconstruction of vascularized microtissue models

Abstract

The limited physiological relevance of current organ-on-a-chip models often stems from an inability to integrate organspecific tissue architectures with functional vascularization. Here, we introduce an open-top microfluidic platform that integrates phase-guide flow control with high-resolution 3D stamps to enable programmable fabrication of complex vascularized microtissues via sequential cell seeding and high-fidelity hydrogel patterning. Our approach enables the creation of three distinct vascularized models: a vascularized tumor model demonstrating enhanced doxorubicin spatial accumulation and pharmacological effects mediated by the functional vascular network; a vascularized colonic model featuring biomimetic crypt architectures that exhibited barrier dysfunction and specific inflammatory cytokine release profiles upon lipopolysaccharide challenge; and a vascularized myocardial model with aligned myocardial bundles showing anisotropic contractility and pharmacological responses. For colonic and myocardial model, a bilayered gel strategy is utilized to ensure the stability of the predefined tissue topology while simultaneously supporting the formation of selfassembly and perfusable vascular network. Each model successfully established functional vascular-tissue interfaces, enabling the study of complex physiological interactions. This work provides a robust and versatile platform for constructing high-fidelity organotypic models that recapitulate critical structural, vascular, and functional features of human tissues, with significant implications for precision medicine and drug screening applications.