A team of bioengineers from the University of California San Diego is developing a bioprinting method that could enable scientists and pharmaceutical companies to easily create human organ models for research purposes and drug screening. At this stage in the research, the UC San Diego team has demonstrated the technique’s ability to produce blood vessel networks that can keep a breast cancer tumor alive outside the body (ex vivo).
The novel bioprinting process begins with the design of a scaffold in Autodesk software, which is then 3D printed on a commercial desktop 3D printer using polyvinyl alcohol, a printable, water-soluble material. Once the scaffold is printed, the researchers coat it in a natural material made up of fibrinogen (a compound found in blot clots) and Matrigel (a commercial form of mammalian extracellular matrix).
The coating is then cured to solidify the natural material and the original 3D printed structure is dissolved, resulting in a form made up of hollow blood vessel-like channels. The channels are then filled with endothelial cells, cells which coat the inside of blood vessels in the body. Finally, cell culture media is flowed through the entire structure to keep the endothelial cells alive.
The bioprinting process was developed with simplicity in mind, as the UC San Diego researchers set out to develop an accessible bioprinting process that would not require extensive additive manufacturing know-how to implement.
“We want to make it easier for everyday scientists—who may not have the specialization required for other 3D printing techniques—to make 3D models of whatever human tissues they’re studying,” said Michael Hu, a bioengineering Ph.D. student at the UC San Diego Jacobs School of Engineering, and the first author of the bioprinting study. “The models would be more advanced than standard 2D or 3D cell cultures, and more relevant to humans when it comes to testing new drugs, which is currently done on animal models.”
Prashant Mali, a bioengineering prof at the UC San Diego Jacobs School of Engineering and the study’s senior author, reinforced this by saying: “You don’t need anything complicated to adopt this into your lab. Our hope is that multiple labs will be able to work with this and experiment with this. The more it gets adopted, the more impact it could have.”
The bioengineering team has already conducted a number of experiments using its bioprinting technique. For instance, it utilized the printed blood vessels to successfully keep a breast cancer tumor alive ex vivo. In this experiment, pieces of tumors were removed from mice and were implanted into the printed blood vessel network as well as into a traditional 3D cell culture. After three weeks, though the cells in the 3D cell culture had mostly died, the tumor tissues in the printed blood vessel structure were still alive.
The researchers also tested their method by printing a vascularized gut model. This network consisted of two channels: one lined with intestinal epithelial cells and one lined with endothelial cells which spiralled around the former. Within two weeks, the gut channel with intestinal epithelial cells started to grow villi—small finger-like projections that line the inside of the intestines.
“This was a proof of concept showing we can culture different types of cells together, which is important if we want to model multi-organ interactions in the body,” explained Hu. “In a single print, we can create two distinct local environments, each keeping a different type of cell alive, and placed close enough together so that they can interact.”
The next phase of the bioprinting project will see the team further refine the process with the goal of optimizing the printed blood vessels and developing vascularized tumor models that closely mimic those that form inside the human body.
The research was recently published in the journal Advanced Healthcare Materials.