Researchers Develop Inexpensive 3D Printing Technique That Generates Molecular Patterns in Hydrogels

Earlier this month, a paper was published by Imperial College London which posited that 3D printing could be made faster, more consistent, and less expensive by combining engineering and molecular science. Now, researchers from Queen Mary University of London (QMUL) have developed new molecular 3D printing technology, which could help recreate complex biological environments that resemble the human body.

QMUL, well-known for its work in making objects disappear with the use of additive manufacturing technology, has created a simple, inexpensive technique, called 3DEAL, that can generate complex molecular patterns in soft matter, like hydrogels, up to the centimeter scale in depth and with a resolution on the microscale.

Fluorescently-labeled protein patterns within different types of 3D hydrogels.

“The human body is largely made up of anisotropic, hierarchical, and mostly three dimensional structures,” said Professor Alvaro Mata, with QMUL’s School of Engineering and Materials Science. “New ways to fabricate environments that can recreate physical and chemical features of such structures would have important implications in the way more efficient drugs are developed or more functional tissue and organ constructs can be engineered.”

Professor Mata was the lead researcher on the project, which was funded by an ERC Starting Grant, and the team recently published the results of its work in a paper, titled “3D Electrophoresis-Assisted Lithography (3DEAL): 3D Molecular Printing to Create Functional Patterns and Anisotropic Hydrogels,” in the journal Advanced Functional Materials; co-authors include Juan P. Aguilar, Michal Lipka, Gastón A. Primo, Edxon E. Licon-Bernal, Juan M. Fernández-Pradas, Andriy Yaroshchuk, Fernando Albericio, and Professor Mata.

The abstract reads, “The ability to easily generate anisotropic hydrogel environments made from functional molecules with microscale resolution is an exciting possibility for the biomaterials community. This study reports a novel 3D electrophoresis-assisted lithography (3DEAL) platform that combines elements from proteomics, biotechnology, and microfabrication to print well-defined 3D molecular patterns within hydrogels. The potential of the 3DEAL platform is assessed by patterning immunoglobulin G, fibronectin, and elastin within nine widely used hydrogels and characterizing pattern depth, resolution, and aspect ratio. Furthermore, the technique’s versatility is demonstrated by fabricating complex patterns including parallel and perpendicular columns, curved lines, gradients of molecular composition, and patterns of multiple proteins ranging from tens of micrometers to centimeters in size and depth. The functionality of the printed molecules is assessed by culturing NIH-3T3 cells on a fibronectin-patterned polyacrylamide-collagen hydrogel and selectively supporting cell growth. 3DEAL is a simple, accessible, and versatile hydrogel-patterning platform based on controlled molecular printing that may enable the development of tunable, chemically anisotropic, and hierarchical 3D environments.”

Electrophoresis refers to the movement of charged particles, in a fluid or gel, under the influence of an electric field, and has been used in combination with 3D printing technology before. QMUL’s 3DEAL technique makes it possible to engineer 3D hydrogel environments with what QMUL refers to as “spatial control of of the chemical composition.”

This gives them the chance to recreate actual biological scenarios, like 3D patterns and molecular gradients, which could have applications in building complex tissue-engineered constructs and designing new drug screening platforms.

“A major advantage of the technique is its robustness and cost-effectiveness,” explained Primo, a PhD student at QMUL. “It is simple and can be used with different types of readily available hydrogels and be patterned with different types of molecules.”

The most important design features of the 3DEAL technique are an electrical field and a porous mask, which moves and localizes different types of molecules inside hydrogels at microscale resolution, within large volumes.

“Fabrication of biomimetic and anisotropic hydrogels exhibiting direction-dependent structure and properties has attracted great interest in the scientific community,” said Dietmar Hutmacher, an expert in Regenerative Medicine Science and Engineering from Queensland University of Technology. “The Mata lab has widened the toolbox with this innovative 3DEAL technology.”

The QMUL research team has a goal of creating variations of the innovative new 3DEAL technique, both to allow for more complex patterning and to focus specifically on in vitro models for biological studies and tissue engineering applications.

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