Airflow‐Assisted 3D Bioprinting of Human Heterogeneous Microspheroidal Organoids with Microfluidic Nozzle

Abstract

Hydrogel microspheroids are widely used in tissue engineering, such as injection therapy and 3D cell culture, and among which, heterogeneous microspheroids are drawing much attention as a promising tool to carry multiple cell types in separated phases. However, it is still a big challenge to fabricate heterogeneous microspheroids that can reconstruct built-up tissues' microarchitecture with excellent resolution and spatial organization in limited sizes. Here, a novel airflow-assisted 3D bioprinting method is reported, which can print versatile spiral microarchitectures inside the microspheroids, permitting one-step bioprinting of fascinating hydrogel structures, such as the spherical helix, rose, and saddle. A microfluidic nozzle is developed to improve the capability of intricate cell encapsulation with heterotypic contact. Complex structures, such as a rose, Tai chi pattern, and single cell line can be easily printed in spheroids. The theoretical model during printing is established and process parameters are systematically investigated. As a demonstration, a human multicellular organoid of spirally vascularized ossification is reconstructed with this method, which shows that it is a powerful tool to build mini tissues on microspheroids.

From Shape to Function: The Next Step in Bioprinting

“…In biofabrication, grafting of short peptide sequences or full‐length proteins selected from the ECM onto the main constituent of the bioink can be exploited. The fine‐tuning of physical properties of the hydrogel combined with the presentation of multiple molecular signals, regulate integrin attachment, (stem) cell differentiation, and create a microenvironment in which multiple cell types can thrive, including organoids and heterocellular spheroids . High‐throughput screening approaches to evaluate vast libraries of functional peptides have been developed and are already applied to hydrogel‐based bioink development .…”

Microfluidic Platforms toward Rational Material Fabrication for Biomedical Applications

“…e) Heterogeneous microspheroidal organoids with spiral distribution of multiple cells formed on a coflow microfluidic device with the assistance of air‐flow. Reproduced with permission . Copyright 2018, John Wiley & Sons.…”

“…Compared to conventional methods to prepare heterogeneous multicellular spheroids that involve of multistep procedures of sequential seeding of different cell types in microwells with dynamically tunable volumes (Figure c), microfluidics have offered a simple yet robust way enabling precise control over the spatial distribution of different cell types by using water‐in‐water‐in‐oil (W/W/O) emulsions as templates (Figure d) . By using a coflow microfluidic device with the assistance of air‐flow directing effects, heterogeneous microspheroidal organoids with spiral distribution of different cell types could be formed (Figure e), offering promising approaches to resemble the complicated anatomy of human tissues/organs . In addition to prepare cell‐encapsulated structures with similar geometries and cell incorporation to human tissues/organs, reconstituting the biochemistries of native extracellular matrix (ECM) by synthetic 3D spherical cell microenvironments via microfluidics is also important.…”

Fabrication and modification of wavy multicomponent vascular grafts with biomimetic mechanical properties, antithrombogenicity, and enhanced endothelial cell affinity

“…Vascular grafts made of decellularized extracellular matrices (ECMs) or rolled cell membranes have been highly recognized in recent years because they resemble the native structure and biological configuration of blood vessels . However, these methods are highly customized, have high cost and variability, and require long cell culture times.…”

“…Vascular grafts made of decellularized extracellular matrices (ECMs) or rolled cell membranes have been highly recognized in recent years because they resemble the native structure and biological configuration of blood vessels. [23][24][25][26] However, these methods are highly customized, have high cost and variability, and require long cell culture times. Therefore, developing cost-effective SDVGs that can fully mimic the properties of blood vessels, prevent thrombosis, and do not require (or require a short) maturation time are in high demand for the practical treatment of CVDs.…”