Rice University & Baylor College of Medicine Researchers 3D Print Functional Capillaries

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A recent paper shows that researchers are making fascinating progress in creating tissue with capillaries that have been 3D printed. While bioprinting is certainly one of the hottest areas of innovation in the scientific arena today–made possible by the concepts behind 3D printing technology–this new study and its findings show that with the initiation of a process called tubulogenesis, the scientists can create capillaries that are functioning and able to transport blood throughout a system.

This latest in bioprinting emanates from work being performed at both Rice University and Baylor College of Medicine. Bioengineers and scientists from both of these distinguished learning institutions have begun combining human endothelial and mesenchymal stem cells to make the capillaries. Their research, ‘Tubulogenesis of co-cultured human iPS-derived endothelial cells and human mesenchymal stem cells in fibrin and gelatin methacrylate gels’ was published in BioMaterials Science last month.

“We implement 3D quantification of the network character and validate that transduced and untransduced iPS-ECs can form tubules in fibrin with or without supporting hMSCs. In addition to natural fibrin gels, we also investigated tubulogenesis in GelMA, a semi-synthetic material that has received increased interest due to its ability to be photopatterned and 3D printed, and which may thus boost development of complex 3D models for regenerative medicine studies,” state the researchers in their abstract.

“Our work bolsters previous findings by validating established tubulogenic mechanisms with commercially available iPS-ECs, and we expect our findings will benefit biologic studies of vasculogenesis and will have applications in tissue engineering to pre-vascularize tissue constructs which are fabricated with advanced photopatterning and three-dimensional printing.”

From the research paper, published in BioMaterials Science.

This research is notable as the team has been able to make such progress with fragile cells that can be drawn from any patient. Not only that, with such patient-specific cells, the researchers see potential for creating tissue and replacement organs. This would allow for transplants without the risk of rejection.

“Our work has important therapeutic implications because we demonstrate utilization of human cells and the ability to live-monitor their tubulogenesis potential as they form primitive vessel networks,” said study lead author Gisele Calderon, a graduate student in Jordan Miller’s Physiologic Systems Engineering and Advanced Materials Laboratory.

“We’ve confirmed that these cells have the capacity to form capillary-like structures, both in a natural material called fibrin and in a semisynthetic material called gelatin methacrylate, or GelMA,” Calderon said. “The GelMA finding is particularly interesting because it is something we can readily 3D print for future tissue-engineering applications.”

Gisele Calderon (left) and Patricia Thai co-authored the research paper recently published in BioMaterials Science. [Image: Jeff Fitlow/Rice University]

While there has been great success in bioprinting and the creation of tissue thus far by researchers, the challenge has remained to fabricate capillaries that can supply the blood.

“Ultimately, we’d like to 3D print with living cells, a process known as 3D bioprinting, to create fully vascularized tissues for therapeutic applications,” said Jordan Miller, assistant professor of bioengineering at Rice. “To get there, we have to better understand the mechanical and physiological aspects of new blood-vessel formation and the ways that bioprinting impacts those processes. We are using 3D bioprinting to build tissues with large vessels that we can connect to pumps, and are integrating that strategy with these iPS-ECs to help us form the smallest capillaries to better nourish the new tissue.”

Tubulogenesis is a process for making capillaries that includes numerous transformations within the endothelial cells. They must form vacuoles and then connect with adjacent cells—forming endothelial-lined tubes to grow into capillaries.

“We expect our findings will benefit biological studies of vasculogenesis and will have applications in tissue engineering to prevascularize tissue constructs that are fabricated with advanced photo-patterning and three-dimensional printing,” said Mary Dickinson, the Kyle and Josephine Morrow Chair in Molecular Physiology and Biophysics at Baylor College of Medicine and adjunct professor of bioengineering at Rice.

This work was the result of dozens of experiments spanning several months. The research team eventually created a process for ‘robust’ tubulogenesis. While there is great potential for 3D printed organs in the future, this type of research may be able to help in immediate research such as drug testing.

“You could foresee using these three-dimensional, printed tissues to provide a more accurate representation of how our bodies will respond to a drug,” Miller said. “Preclinical human testing of new drugs today is done with flat two-dimensional human tissue cultures. But it is well-known that cells often behave differently in three-dimensional tissues than they do in two-dimensional cultures.

“There’s hope that testing drugs in more realistic three-dimensional cultures will lower overall drug development costs. And the potential to build tissue constructs made from a particular patient represents the ultimate test bed for personalized medicine. We could screen dozens of potential drug cocktails on this type of generated tissue sample to identify candidates that will work best for that patient.”

Discuss in the 3D Printed Capillaries forum at 3DPB.com.

[Source: Phys.Org]

 

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