Photonics helps bioprinting translate to clinical use

14 Jun 2023

Utrecht team addresses three significant hurdles facing biofabrication methods.

Laser-based bioprinting is already part of novel medical research techniques, assisting with the precise placement of cells for study and their transfer from one location to another.

Clinical and larger scale uses for the same techniques are also attractive for a number of demanding applications, perhaps ultimately being used to grow organs from patients' own cells and address donor shortages.

Printing living tissues and cells remains very complicated, however, with a number of acknowledged challenges remaining to be solved before highly detailed and differentiated functional tissues suitable for implant can be made on clinically relevant scales.

A research group at University Medical Center Utrecht (UMCU) has now announced three individual innovations in the field of bioprinting, which together should contribute to the technique's progress towards broad clinical use.

The research focused on volumetric additive bioprinting, in which a laser selectively solidifies light-sensitive gel to from intricate 3D structures within which cells are located. Although this process can be rapid, controlling which cell ends up where is difficult, and once in place the cells might not interact with each other freely, according to the project team.

One Utrecht finding, published in Advanced Materials Technologies, involved the formulation of a novel photo-cross-linkable norbornene-modified gelatin and suitable modifications to the irradiation regime used to solidify it. Prematurely stopping the illumination, for example, can avoid cross-linking of out-of-target regions and reduce printing artefacts.

"This work really takes the first steps into the development and characterization of smart materials that allow biochemical editing in 3D," said Marc Falandt of UMCU. "It could allow us to closely mimic the complex biochemical environment of native tissues and organs with our 3D bioprints."

Printing blood vessels

In a second paper, published at bioRxiv as a preprint, UMCU described a novel technique termed embedded extrusion-volumetric printing (EmVP). In this method, the use of granulated resins allows cells to be positioned as desired using an extrusion approach prior to illumination and cross-linking of the resin.

This needs careful control of the illumination procedure, but the project successfully used the thermal properties of the microgel when irradiated as a stimuli to be sensed by the embedded cells, offering a way to precisely tune the mechanical and optical properties of the final product.

A third UMCU breakthrough, published in Advanced Materials, combined two distinct bioprinting techniques, bioprinting and melt electrowriting, to create functional blood vessels while avoiding the inherent structural weakness of vessel structures made using just one method.

"Melt electrowriting works by directing a narrow filament of molten biodegradable plastic to produce intricate scaffolds that are mechanically strong and able to deal with force," commented UMCU. "The downside is that they can't be printed with cells in there directly, because of the high temperatures involved. Therefore, volumetric bioprinting was used to solidify cell-laden gels onto the scaffolds."

In proof-of-principle trials using two differently labeled stem cells, UMCU was able to print a blood vessel with two layers of stem cells, and then seeded epithelial cells in the center to cover the lumen of the vessel.

"What we now need to do is replace the stem cells with functional cells that are part of a real blood vessel," said Gabriel Größbacher of UMCU. "That means adding muscle cells and fibrous tissue around the epithelial cells. Our goal now is to print a functional blood vessel."