Numerical modeling of hydrogel scaffold anisotropy during extrusion-based 3D printing for tissue engineering

TL;DR

This paper develops a multiscale numerical model to predict how hydrogel scaffold anisotropy develops during extrusion-based 3D printing, aiding the design of tissue engineering scaffolds with desired cellular responses.

Contribution

It introduces a micro-macro modeling framework using the Fokker-Planck equation to simulate polymer orientation during hydrogel extrusion, advancing scaffold anisotropy prediction.

Findings

High shear rates align hydrogel constituents during extrusion.

Interaction coefficient C_i improves orientation prediction accuracy.

The model offers a computationally feasible tool for process optimization.

Abstract

Extrusion-based 3D printing is a widely utilized tool in tissue engineering, offering precise 3D control of bioinks to construct organ-sized biomaterial objects with hierarchically organized cellularized scaffolds. The internal organization of scaffold constituents must replicate the structural anisotropy of the targeted tissue to effectively promote cellular behavior during 3D cell culture. The choice of polymers in the bioink and extrusion process topological properties significantly impact tissue engineering constructs' structural anisotropy and cellular response. Our study employed a hydrogel bioink consisting of fibrinogen, alginate, and gelatin, providing biocompatibility, printability, and shape retention post-printing. Topological properties in flowing polymers are determined by macromolecule conformation, namely orientation and stretch degree. We utilized the micro-macro approach to describe hydrogel macromolecule orientation during extrusion, offering a two-scale fluid behavior description. The study aimed to use the Fokker-Planck equation to represent constituent population (polymer chain) state within a hydrogel's representative elementary volume during extrusion-based 3D printing. Our findings indicate that a high shear rate drives constituent orientation in tubular nozzle syringe setups, overcoming fluid rheological behavior. Additionally, the interaction coefficient (C_i), representing microscopic fluid particle interaction, surpasses hydrogel behavior for constituent orientation prediction. This approach provides an initial but robust framework to model scaffold anisotropy, enabling optimization of the extrusion process while maintaining computational feasibility.