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3D bioprinting complex vessel networks for implantable tissues

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Ali Khademhosseini, a bioengineering professor at UCLA specializing in tissue engineering and bioprinting, and his team have developed a new and innovative technique for bioprinting tubular structures that mimic complex vessel networks and ducts. The breakthrough research, recently published in the journal Advanced Materials, could enable the bioprinting of tissues for implanting or drug testing.

The project, supported by the National Institutes of Health, is being pursued in collaboration with researchers from Harvard University and the Brigham and Women’s Hospital. It follows on Khademhosseini’s previous bioprinting effort in which he developed a customized multi-material bioprinter designed for producing complex artificial tissues.

While there are a number of efforts in the biomedical field to integrate vessels into bioprinted tissues, not many have succeeded in matching the complexity and variability of natural blood vessel networks. The recent method proposed by the joint research team reportedly comes closer to mimicking complex vessel networks than ever before.

“The vessels in the body are not uniform,” explained Yu Shrike Zhang, PhD, senior author on the study and an associate bioengineer in BWH’s Department of Medicine. “This bioprinting method generates complex tubular structures that mimic those in the human system with higher fidelity than previous techniques.”

The process consists begins with specialized bioink made from human cells and a hydrogel material. The hydrogel, composed of hydrophilic polymers, has been optimized so that it encourages human cells to proliferate throughout the ink. Next, a cartridge of the bioink is loaded into a bioprinter equipped with a nozzle customized for continuously printing tubular structures with up to three layers.

Crucially, the tubular structures printed using the novel method are perfusable, meaning that fluids and nutrients can effectively be transported through them to be carried throughout the tissue. Blood vessels, of course, play a critical role in bringing nutrients throughout organic tissue and enabling it to thrive. In artificial tissues, the same functionality is required.

In their study, the researchers successfully printed artificial vascular and urothelial tissues. For the latter, they used a combination of human urothelial and bladder smooth muscle cells, while for the vascular tissue they mixed human endothelial cells and smooth muscle cells with the hydrogel.

As the researchers further establish their method for bioprinting tissues and blood vessel constructs, the ultimate aim is to fabricate complex artificial tissues which are patient-specific (in other words, created from their cells).

“3D printing allows you to make tissues that are actually the same shape as the defect that the patient has,” explained Khademhosseini, the Levi James Knight, Jr. Chair in Engineering at UCLA. “If we can make tissues, not only can we transplant them into people and fix their diseases, but also we can use the tissues outside the body to test drugs on patients and on the tissues of the patients to see the drug is going to be useful or not. This allows us to make any kind of therapy specialized to that individual person.”

Challenges do remain, however. For instance, the team must ensure that the bioprinted tissues are implantable and will remain viable for long periods of time inside the body. Still, the researchers are confident that this challenge and others will be solved in the near future.

“We’re currently optimizing the parameters and biomaterial even further,” concluded Zhang. “Our goal is to create tubular structures with enough mechanical stability to sustain themselves in the body.”

3D bioprinting complex vessel networks for implantable tissues