Development of a functional airway-on-a-chip by 3D cell printing

Abstract

We used 3D cell printing to emulate an airway coupled with a naturally-derived blood vessel network in vitro. Decellularized extracellular matrix bioink derived from porcine tracheal mucosa (tmdECM) was used to encapsulate and print endothelial cells and fibroblasts within a designated polycarprolactone (PCL) frame. Providing a niche that emulates conditions in vivo, tmdECM gradually drives endothelial re-orientation, which leads to the formation of a lumen and blood vessel network. A fullydifferentiated in vitro airway model was assembled with the printed vascular platform, and collectively reproduced a functional interface between the airway epithelium and the vascular network. The model presented respiratory symptoms including asthmatic airway inflammation and allergen-induced asthma exacerbation in physiological context. Because of the adaptable and automated nature of direct 3D cell printing, we expect that this will have relevance in vivo and high reproducibility for production of high-content platforms for preclinical trials in biomedical research.

Recreating Physiological Environments In Vitro: Design Rules for Microfluidic‐Based Vascularized Tissue Constructs

“…Shim et al built a sophisticated multihead 3D printer that enables dual extrusion of bioinks which therefore allows simultaneous printing of two different cell types . Through this method, Park et al developed bioinks embedded with endothelial cells and another with lung fibroblasts . As a result, they developed a functional in vitro lung‐on‐a‐chip through cell‐loaded 3D extrusion, which successfully recapitulated physiological responses.…”

Vascularized Lower Respiratory-Physiology-On-A-Chip

“…These studies showed that the vascularized airway-on-a-chip by 3D bioprinting more faithfully reflects the structural and functional resemblance of the actual tissue. Park et al [75] applied 3D bioprinting to simply and quickly construct a chip. To mimic the microenvironment of a trachea, decellularized trachea ECM bioink was used for printing.…”

“…The poly (I: C) triggered inflammatory responses similar to in vivo. In addition, Park et al [75] used 3D bioprinting to mimic the combination of airways with vascular networks in vitro. They developed a vascular platform via 3D printing of cell-containing dECM bioinks and also integrated them with epithelial models.…”

Processed Tissue–Derived Extracellular Matrices: Tailored Platforms Empowering Diverse Therapeutic Applications

“…While the physical properties of synthetic polymers are easily controllable, they generally exhibit poor biocompatibility, toxic degradation products, and lack of bioactivity . The utilization of dECM as a bioink for 3D printing of tissue engineered constructs is, therefore, increasingly being employed by numerous research groups . For its printing, the dECM must first be solubilized or “fluidized” to enable its extrusion through the printing apparatus.…”