Complexation-induced resolution enhancement of 3D-printed hydrogel constructs

Jiaxing Gong,Arturo López,Wanlu Li,Jennifer Manríquez,Ruiquan Li,Clément Delavaux,Yu Shrike Zhang,Huiming Wang,Pamela E Capendale,Carl C L Schuurmans,Jingwei Xie,Mengfei Yu,Valentín Huerta ,Rosalinde Masereeuw,Anne Metje Van Genderen,Tina Vermonden,Feng Cheng,Jacqueline Jialu He,Hongbin Li,Shikha Sebastian,Xia Cao

doi:10.1038/s41467-020-14997-4

Abstract

Three-dimensional (3D) hydrogel printing enables production of volumetric architectures containing desired structures using programmed automation processes. Our study reports a unique method of resolution enhancement purely relying on post-printing treatment of hydrogel constructs. By immersing a 3D-printed patterned hydrogel consisting of a hydrophilic polyionic polymer network in a solution of polyions of the opposite net charge, shrinking can rapidly occur resulting in various degrees of reduced dimensions comparing to the original pattern. This phenomenon, caused by complex coacervation and water expulsion, enables us to reduce linear dimensions of printed constructs while maintaining cytocompatible conditions in a cell type-dependent manner. We anticipate our shrinking printing technology to find widespread applications in promoting the current 3D printing capacities for generating higher-resolution hydrogel-based structures without necessarily having to involve complex hardware upgrades or other printing parameter alterations.

Highlights

Three-dimensional (3D) hydrogel printing enables production of volumetric architectures containing desired structures using programmed automation processes
When a hyaluronic acid methacrylate (HAMA) hydrogel is placed in the presence of polycations of high charge densities, such as chitosan, a type of glucosamine featuring reasonable biocompatibility and densely cationic nature due to the abundantly available amino groups[11], charge compensation occurs leading to expulsion of water and eventual size reduction of the HAMA hydrogel (Fig. 1a and Supplementary Fig. 1)
That when a solution of positively charged lysozyme was introduced to microfluidics-fabricated HAMA microspheres, the size of these microspheres was decreased due to a mechanism akin to complex coacervation, facilitating their use in drug delivery[13]

Summary

Introduction

Three-dimensional (3D) hydrogel printing enables production of volumetric architectures containing desired structures using programmed automation processes. Some other printing strategies, such as those based on light (e.g., two-photon lithography) can achieve varying degrees of higher resolutions[6], their instrumentation is usually complicated limiting the broader adoption for general use. To this end, efforts have conventionally been focused on improving the printer hardware or ink properties. While efficient for two-photon lithography, this method is not amenable to most other 3D printing modalities due to the necessity of a preexisting, swollen hydrogel matrix to allow anchoring points for secondary biomolecules or inorganic species subsequently patterned in the volumetric space Such shrinking is unstable and would revert once the stimulus is removed. We anticipate wide adoption of this technology in future printing of acellular or cellularized structures with further optimizations

Objectives

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Conclusion