28 May 2025
Femtosecond source produces precise, stable channels for blood supply in tissue models.
A project from TU Wien (Technical University of Vienna, Austria) has demonstrated how laser patterning can be used to create microvascular channels within microfluidic chips.The breakthrough, described in Biofabrication, could assist the manufacture of organs-on-chips (OoC), 3D models replicating the in vitro functions of human organs or tissues.
Although OoC technology has helped researchers to understand physiological functions under controlled laboratory conditions, the complexities of manufacturing and embedding vascular networks within growing tissue samples have remained challenging, noted TU Wien.
The best methods for doing this until now have involved self-assembly of cells within carefully created environments, but this can cause vessel geometry to vary significantly from one sample to another, interfering with the defined experimental conditions that researchers are looking for. Precise and controlled laser patterning should be a better way.
TU Wien's approach involved using a femtosecond near-IR source to pattern 3D hollow cylindrical channels, 100 microns in diameter and 200 microns apart, through ablation of a collagen matrix in a microfluidic chip. Endothelial cells were subsequently introduced into the laser-patterned microchannels, allowing them to adhere and become incorporated within the engineered structures.
The team also optimized the hydrogel material employed, to make sure that the channels remained structurally sound after the laser had done its work, and so reduce the likelihood of structural change or degradation once the living cells were in place and growing.
Organ-on-chip for new drug development
Instead of using a standard single-step gelation method, the team used a two-step thermal curing process in which the hydrogel is warmed in two phases using different temperature, rather than just one. This alters its network structure, according to TU Wien, producing a more stable material. The vessels formed within such a material remain open and maintain their shape over time.
Trials showed that the artificial blood vessels created this way were successfully colonized by endothelial cells, which later reacted to inflammation in the same way as cells in the body.
"We have shown that we can produce artificial blood vessels that can actually be perfused," commented Aleksandr Ovsianikov from TU Wien. "But the more important thing is to have developed a scalable technology that can be used on an industrial scale. It takes only 10 minutes to pattern 30 channels, which is at least 60 times faster than other techniques."
In collaboration with Japan's Keio University, the project also applied its technique to create a liver-on-chip model designed to mimic a hepatic lobule of the liver and its microvascular network.
Published separately in Materials Today Bio, the team's results showed that laser patterning produced a lobule-on-chip model closely mimicking the in vivo arrangement of the central vein and sinusoids in the natural organ.
"Replicating the liver’s dense and intricate microvasculature has long been a challenge in organ-on-chip research," said Masafumi Watanabe from Keio University.
"By building multiple layers of microvessels spanning the entire tissue volume, we were able to ensure adequate nutrient and oxygen supply, which in turn led to improved metabolic activity in the liver model. We believe that these advancements bring us a step closer to integrating organ-on-chip technology into preclinical drug discovery."
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