Algae give life to 3D engineered fabrics

3D bioprinted algae can be harnessed as a sustainable source of oxygen for human cells in engineered vascularized tissues, researchers report Nov.18 in the journal It matters. They incorporated bioprinted photosynthetic algae, along with human liver-derived cells, into a 3D hydrogel matrix to create honeycomb-shaped tissues with lobules, similar to human liver. In the future, the researchers say, the eco-friendly and cost-effective 3D bioprinting approach could have potential for applications such as disease modeling, drug development, regenerative and personalized medicine, and even food engineering.

“The study is the first true example of symbiotic tissue engineering that combines plant cells and human cells in a physiologically meaningful way, using 3D bioprinting,” says senior study author Y. Shrike Zhang (@shrikezhang) a bioengineer at Harvard Medical School and Brigham and Women’s Hospital. “Our study provides a unique example of how we can leverage the symbiotic strategy, very often seen in nature, to promote our ability to design functional human tissues.”

There is a growing demand for artificial tissues to replace those that have been damaged in order to restore organ function and, over the past decade, 3D bioprinting techniques have been used to fabricate tissue scaffolds for biomedical and tissue engineering applications. This approach typically involves depositing a bioink onto a surface to produce 3D structures with desired architectures and shapes to recapitulate organs and tissues, including the vascular system, which plays a vital role in the transport of oxygen and nutrients throughout the body. A bioink is essentially a hydrogel containing living cells, biomaterials, and other growth supplements. It mimics the extracellular matrix of the desired tissue and supports the growth of embedded cells.

Despite advances in 3D tissue fabrication, the main limitation has been the maintenance of sufficient oxygen levels throughout the engineered tissue to promote cell survival, growth, and functioning. Researchers have tried to address this problem by incorporating oxygen-releasing biomaterials, but these typically don’t work long enough and are sometimes toxic to cells because they produce molecules like hydrogen peroxide or other reactive oxygen species. “A method of enabling the sustained release of oxygen from within engineered tissues is urgent,” says Zhang.

To meet this demand, Zhang and his colleagues developed an algae-based 3D bioprinting method to embed vascular patterns within engineered tissues and provide a sustainable source of oxygen for human cells in the tissues. Specifically, they used photosynthetic single-celled green algae called Chlamydomonas reinhardtii. This symbiotic strategy also benefits algae, whose growth is partially supported by carbon dioxide released from surrounding human cells.

The first step involved 3D bioprinting of the algae. Researchers encapsulated C. reinhardtii in a bioink composed primarily of cellulose, the main structural component of plants, algae and fungi. The bioink was loaded into a syringe fitted with a needle and extrusion bioprinting was performed using a bioprinter.

Next, the researchers incorporated both bioprinted algae and human liver-derived cells into a 3D hydrogel matrix. Bioprinted C. reinhardtii released oxygen photosynthetically and improved the vitality and functions of human cells, which grew to a high density and produced liver specific proteins. “High cell densities in engineered vascularized human tissues were difficult to achieve before,” says Zhang.

Finally, the researchers used the cellulase enzyme to degrade the cellulose-based bioink, then filled the hollow microchannels left with human vascular cells to create vascular networks in liver-like tissue. “The development of such a fugitive bioink that allows for initial oxygenation and subsequent vessel formation within a single tissue construct has not been reported before,” Zhang says. “This is a critical step towards the successful engineering of vital and functional tissues.”

Eventually, vascularized and oxygenated 3D tissues have the potential for a future implant to achieve tissue regeneration in humans. These tissues could also be used for drug screening and development, the study of disease mechanisms, and possibly personalized medicine if patient-specific cells are used.

Another potential application of 3D bioprinting technology is food engineering. Microalgae are a rich source of proteins, carbohydrates, polyunsaturated fatty acids, carotenoids, essential vitamins and minerals. These bioactive compounds could be incorporated into innovative and cultured food products to increase their nutritional value and promote health.

But in the meantime, more effort is needed to optimize the method. For example, the culture media could be improved to facilitate the growth of both C. reinhardtii and human cells, and the lighting conditions could be adjusted to optimize the oxygen supply from the algae. Furthermore, detailed studies on the biosecurity, toxicity and immunocompatibility of algae will be important for clinical translation in the future. “This technology cannot be used immediately by humans,” says Zhang. “It’s still a proof of concept and will require significant follow-up studies to translate.”

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This work was supported by the National Institutes of Health, the National Science Foundation, and the New England Anti-Vivisection Society.

Matter, Maharjan et al.: “Bionic photosynthetic oxygenation within 3D bioprinted vascularized tissues”
https://www.cell.com/matter/fulltext/S2590-2385(20)30576-2

It matters (@Matter_CP), published by Cell Press, is a new journal for multidisciplinary and transformative research in materials sciences. Articles explore scientific advances across the materials development spectrum, from fundamentals to application, nano to macro.
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