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 organ-specific 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 <i>via</i> 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 self-assembly and a 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.