Direct Cell Writing of 3D Microorgan for <i>In Vitro</i> Pharmacokinetic Model

TLDR

In vitro pharmacokinetic models are emerging in tissue engineering for drug screening and toxicology. The study aims to develop an in vitro pharmacokinetic model that realistically predicts human responses to drug administration and toxic exposure. The authors fabricate a 3D microorgan via automated syringe‑based layered direct cell writing and integrate it into a microscale microfluidic device fabricated by soft lithographic micropatterning, creating a physiologically relevant pharmacokinetic model. The DCW process successfully produces reproducible 3D hydrogel constructs integrated into microfluidic devices, yielding predictable cell viability, proliferation, and enhanced functionality compared to traditional culture.

Abstract

A novel targeted application of tissue engineering is the development of an in vitro pharmacokinetic model for drug screening and toxicology. An in vitro pharmacokinetic model is needed to realistically and reliably predict in vivo human response to drug administrations and potential toxic exposures. This paper details the fabrication process development and adaptation of microfluidic devices for the creation of such a physiologically relevant pharmacokinetic model. First, an automated syringe-based, layered direct cell writing (DCW) bioprinting process creates a 3D microorgan that biomimics the cell's natural microenvironment with enhanced functionality. Next, soft lithographic micropatterning techniques are used to fabricate a microscale in vitro device to house the 3D microorgan. This paper demonstrates the feasibility of the DCW process for freeform biofabrication of 3D cell-encapsulated hydrogel-based tissue constructs with defined reproducible patterns, direct integration of 3D constructs onto a microfluidic device for continuous perfusion drug flow, and characterization of 3D tissue constructs with predictable cell viability/proliferation outcomes and enhanced functionality over traditional culture methods.