QMUL Researchers Use Inkjet 3D Printing and Self-Assembly Technologies to Create Constructs Using Cells and Molecules

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Typically when we hear about self-assembling technology in the 3D printing world, it’s usually referring to robots or pieces of furniture that can build themselves. But researchers from Queen Mary University of London (QMUL) are continuing to research molecular 3D printing, and recently developed a new technique, which uses molecular self-assembly, to create constructs that look like biological structures, using the molecules and cells typically found in natural human tissues. The method also uses inkjet 3D printing technology to build the complex structures out of molecules, similar to assembling Lego pieces.

“The technique opens the possibility to design and create biological scenarios like complex and specific cell environments, which can be used in different fields such as tissue engineering by creating constructs that resemble tissues or in vitro models that can be used to test drugs in a more efficient manner,” explained Professor Alvaro Mata, from the university’s School of Engineering and Materials Science.

Researchers can observe how cells work within their native environments, as the structures are embedded in an ink similar to where cells live, giving them the potential to behave as they normally would in the human body. In addition to this observation, the team could also potentially study real-life biological scenarios, like how immune cells interact with other cells or where exactly cancer grows, in order to develop new drugs.

Gel structures made using hierarchical biofabrication. [Image: Clara Hedegaard]

The team recently published a paper on their work, titled “Hydrodynamically Guided Hierarchical Self-Assembly of Peptide-Protein Bioinks,” in the Advanced Functional Materials journal; co-authors include QMUL’s Clara L. Hedegaard, Estelle C. Collin, and Carlos Redondo-Gómez; Luong T. H. Nguyen and Kee Woei Ng with Nanyang Technological University; Alfonso A. Castrejón-Pita from the University of Oxford; and J. Rafael Castrejón-Pita and Mata with QMUL.

The abstract reads, “Effective integration of molecular self-assembly and additive manufacturing would provide a technological leap in bioprinting. This article reports on a biofabrication system based on the hydrodynamically guided co-assembly of peptide amphiphiles (PAs) with naturally occurring biomolecules and proteins to generate hierarchical constructs with tuneable molecular composition and structural control. The system takes advantage of droplet-on-demand inkjet printing to exploit interfacial fluid forces and guide molecular self-assembly into aligned or disordered nanofibers, hydrogel structures of different geometries and sizes, surface topographies, and higher-ordered constructs bound by molecular diffusion. PAs are designed to co-assemble during printing in cell diluent conditions with a range of extracellular matrix (ECM) proteins and biomolecules including fibronectin, collagen, keratin, elastin-like proteins, and hyaluronic acid. Using combinations of these molecules, NIH-3T3 and adipose derived stem cells are bioprinted within complex structures while exhibiting high cell viability (>88%). By integrating self-assembly with 3D-bioprinting, the study introduces a novel biofabrication platform capable of encapsulating and spatially distributing multiple cell types within tuneable pericellular environments. In this way, the work demonstrates the potential of the approach to generate complex bioactive scaffolds for applications such as tissue engineering, in vitro models, and drug screening.”

Cells spreading on the outside of a PA based scaffold. [Image: Clara Hedegaard]

The structures can be manufactured with molecular precision, under digital control, which gives the researchers the ability to create constructs that mimic tissues or body parts for work in regenerative medicine and tissue engineering (TE).

According to the paper, “Additive manufacturing (3D printing) has enabled the fabrication of reproducible and structurally complex scaffolds, overcoming a major limiting factor in TE. Within the field of bioprinting (additive manufacturing with living matter), droplet-on-demand (DoD)-based inkjet printing has shown promise owing to its precision, flexibility, and compatibility with cells. However, many of the printing inks used in extrusion and inkjet based bioprinting for TE are constrained by stringent printing requirements (e.g., low viscosity, high gel stiffness, fast gelation time, and biocompatibility), which significantly limits the choice of materials and the opportunity to build with, or even recreate, key ECM components.”

An example of the print-head precision: (left) a square, (middle) a star, and (right) an array for sheet formation, all done with water and a 500 µm nozzle.

A major goal of tissue engineering is the ability to recreate features of the natural ECM which can signal specific cells. Many different approaches have been taken to develop bioinks with better support of cell culture, such as using spheroids as building blocks, synthetic materials supplemented with growth factors, and now the QMUL team’s method, which integrates the micro- and macroscopic control of structural features, provided by 3D printing, with the molecular and nano-scale control that’s possible with self-assembly technology.

“This method enables the possibility to build 3D structures by printing multiple types of biomolecules capable of assembling into well defined structures at multiple scales,” said PhD student and lead author Hedegaard. “Because of this, the self-assembling ink provides an opportunity to control the chemical and physical properties during and after printing, which can be tuned to stimulate cell behaviour.”

The self-assembly and 3D printing technologies used in the team’s technique look to take on an existing limitation in 3D printing in that common inks have a limited capacity for stimulate the cells being printed.

Discuss this and other 3D printing topics at 3DPrintBoard.com or share your thoughts below. 

[Source: Phys.org]


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