(China 3D Printing) Nov. 25, 2020 - Scientists at Harvard Medical School have developed a new algae-based bioink that shows enhanced cellular viability once it is 3D printed into soft tissue structures. The team formed the bioink by combining photosynthetic algae and human liver cells into a hydrogel matrix, which was then used to 3D print hexagonal structures with realistic liver "lobules. Because of the algae's natural tendency to release oxygen, the bioimprinted human cells were able to multiply, display increased functionality, and produce liver-specific proteins.
In the future, the researchers believe their new bioprinting technology could be applied to areas ranging from drug development and personalized medicine to algae-based healthy snacks. This study is the first real-world example of symbiotic tissue engineering combining plant and human cells in a physiologically meaningful way," said Y. Shrike Zhang, senior author of the paper. Our research provides a unique example of how we can use symbiotic strategies commonly found in nature to enhance our ability to engineer functional human tissues."
The research team's hexagonal bioprinted structure (shown here) was shown to support 92% of the cells within 7 days
The research team's hexagonal bioprinted structures (shown) were shown to be able to support 92 percent of the cells in 7 days. Photo courtesy of the journal Matter Matters.
The urgent need for bio-3D printed tissue
The shortage of organ donors remains a major problem worldwide, with only about 10 percent of transplant needs currently being met, according to the World Health Organization. As a result, there is a growing urgency to develop artificial alternatives, and 3D bioprinting has made significant progress in this area in recent years. Despite the different approaches researchers have taken, the resulting cell-filled structures often lack the cell viability that would make them useful in end-use scenarios. For example, scientists at Washington State University (WSU) have also created a naturally enhanced hydrogel that is not yet ready for medical use.
Cell viability depends heavily on their level of oxygen exposure, and uniform distribution of oxygen has been shown to contribute to cell growth. However, previous attempts to use oxygen-distributing biomaterials to oxygenate cell-filled hydrogels have been halted due to damaging byproducts and inconsistent release profiles. To overcome these limitations, the team adapted an algae-rich hydrogel developed at the Technical University of Dresden to contain a higher concentration of cellulose, according to China3DPrint.com. The natural polymer not only provided integrity to the scientists' hydrogel, but ultimately proved capable of enriching the tissue they 3D printed.
The scientists hope that their combined 3D printing and cross-linking approach (shown here) will form the basis for a tissue scaffold with enhanced cell viability
Scientists hope their combined 3D printing and cross-linking approach (shown here) will form the basis for a tissue scaffold with enhanced cell viability. Image from the journal Matter Matters.
Harvard team's algae hydrogel
The team created their hydrogel by combining carboxymethylcellulose with gelatin, PVA and alginate and adjusting the amount of each to optimize the viscosity of the ink. Once the team determined the ideal mixture, they used it to 3D print a series of honeycomb structures, each containing seven hexagonal leaflets.
During the printing process, the researchers created a series of six, ten and twenty layers of thin paper that formed a 3D tubular grid-like pattern. The scientists then mixed varying levels of Rhodophyta photosynthetic algae and 10 percent fetal bovine serum into the additive constructs and observed encouraging results. The bioprinted algae released oxygen in a photosynthetic manner, thus enhancing the viability and function of the liver cells without affecting the printability of the bioink. In addition, in a final step, the team added cellulase to dissolve its bioink and found that it left hollowed-out microchannels.
Filling these chambers with human vascular cells allowed the scientists to create liver-like tissues that exhibited good cell growth and produced natural proteins. Cell structures that did not contain algae infusions were able to show only 70 percent survival, while those that contained algae infusions were able to show up to 92 percent survival," concluded Zhang. "The development of such an escaped bioink that allows initial oxygenation and subsequent vascular formation in a single tissue construct has not been reported before. This is a critical step towards the successful completion of viable and functional tissue engineering."
Benefits of using algae
Algae are not only healthy for humans, but also play a role in reducing greenhouse gas emissions, and their green literacy is increasingly making it the subject of 3D printing-related research. Scientists from Wageningen University in the Netherlands and the University of Valencia in Spain have deployed algae algae to 3D print a variety of healthy cereal snacks. The team believes they can customize the shape, texture and color of the algae food to make it more attractive.
Elsewhere, a joint team from the University of Cambridge and the University of San Diego San Diego has 3D bioprinted structures that mimic coral, capable of growing microalgae. By fine-tuning the cultivation of algae, the scientists aim to develop a way to reduce greenhouse gas emissions in developing countries.