The frontier of biomedical research is rapidly advancing with the development of “organs-on-a-chip,” or microphysiological systems, which offer unprecedented accuracy in studying human biology outside of living organisms. These miniature tissue structures, cultivated within precisely controlled microfluidic chips, are poised to revolutionize drug discovery and our understanding of complex biological interactions. However, a significant hurdle has persisted: the challenge of reliably and reproducibly creating functional blood vessels within these artificial mini-organs. Now, a collaborative effort has achieved a breakthrough in laser-precision photonics, leveraging ultrashort laser pulses to rapidly fabricate intricate, perfusable blood vessel networks that behave just like their natural counterparts.
For accurate biomedical research, especially when investigating drug transport, metabolism, and absorption in various human tissues, a sophisticated vascular network is essential. Ideally, these delicate blood vessels need to be formed directly within specialized materials known as hydrogels. Hydrogels mimic the permeable nature of natural tissues while providing crucial structural support for living cells. By creating tiny channels within these hydrogels, researchers can guide the precise formation of blood vessel-like structures, allowing endothelial cells – the very cells that line real blood vessels – to colonize and form functional, perfusable networks. The major challenge until now has been controlling the exact geometry of these microvascular networks; self-organization methods often result in significant variations between samples, hindering reproducible and controlled experiments vital for reliable scientific outcomes.
The team overcame this geometric control challenge by employing advanced laser technology, specifically ultrashort femtosecond laser pulses. This laser-precision photonics approach allows for the direct “writing” of highly precise 3D structures directly into the hydrogel, offering both speed and efficiency. The ability to create channels spaced as little as a hundred micrometers apart is critical for replicating the natural density of blood vessels found in specific organs.
Beyond precision, the artificial blood vessels must also be structurally stable once populated with living cells, as cells actively remodel their environment, which could lead to vessel deformation or collapse. To address this, the researchers improved the hydrogel preparation process itself. Instead of a standard single-step gelation, they implemented a two-step thermal curing process with different temperatures. This innovative laser-precision photonics approach alters the hydrogel’s network structure, resulting in a more robust and stable material. Consequently, the fabricated vessels remain open and maintain their shape over extended periods, ensuring consistent experimental conditions.
This new scalable laser-precision photonics technology is a significant step forward, capable of patterning 30 channels in just 10 minutes – a remarkable 60 times faster than other existing techniques. Crucially, the researchers demonstrated that these artificial blood vessels, once colonized by endothelial cells, exhibit natural biological responses. For example, they react to inflammation by becoming more permeable, precisely mirroring the behavior of real blood vessels in the body. This validated functionality is paramount for establishing lab-on-a-chip technology as an industry standard in various fields of medical research.
As a compelling demonstration, the team successfully vascularized a liver model, creating a liver lobule-on-chip. This sophisticated laser-precision photonics model incorporates a precisely controlled 3D vascular network that closely mimics the complex arrangement of central veins and sinusoids found in vivo. Replicating the liver’s dense and intricate microvasculature has long been a significant challenge. By building multiple layers of microvessels throughout the tissue volume, the researchers ensured adequate nutrient and oxygen supply, leading to improved metabolic activity in the liver model. These advancements represent a pivotal step towards integrating organ-on-a-chip technology into preclinical drug discovery, offering researchers more reliable models to study disease, drug interactions, and ultimately, pave the way for better treatments and healthcare in the future.
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