In a move that could one day lead to artificial transplant organs and sophisticated regenerative therapies, a UCLA team led by bioengineer Ali Khademhosseini has developed a new technique for printing complex bio-tissues using multiple materials. Using a specially modified 3D printer, it promises to one day create therapeutic biomaterials on demand.
Organ transplants and other advanced tissue treatments face a seemingly impassable bottleneck. There are only a finite number of organ donors or other sources of biomaterials, and even in the best of cases the organs and tissues are never perfectly compatible with the recipient and may not be suitable for purpose.
Ideally, bioengineers would like to bypass conventional sources altogether and grow organs and tissues in the lab. This would not only provide the medical community with an unlimited supply of healthy, sterile materials, but would also allow doctors and surgeons to have biomaterials made to their specifications.
The trouble is, living tissue is incredibly complex with many different kinds of cells, blood vessels, nerves, and mechanical structures. Try to grow a heart in a Petri dish by mixing some heart muscle cells with nutrients and all you'll get is a lump of cells that will soon cease to divide.
The alternative is to build a scaffold out of biocompatible material like the hydrogels poly(ethylene glycol) diacrylate (PEGDA) and gelatin methacryloyl (GelMA). This scaffold, which mimics the structure of living tissue, acts like the cartilage in an infant's body. When first born, much of a human baby's skeleton is cartilage, but as it grows and matures, this is replaced by bone tissue. In the artificial tissue, stem cells are introduced that grow into the scaffolding and replace it.
One technique for creating these scaffolds is called stereolithography. This is a light-based process where hydrogel mixed with stem cells is laid down by a 3D printer as a beam of light causes molecular bonds to form, hardening the gel.
The UCLA bioprinter designed by Khademhosseini is based on this technique, but it also incorporates a bespoke microfluidic chip about the size and shape of a microchip. This has multiple inlets, so it can print with more than one cell-infused material at a time. This is joined by a digital micromirror made of an array of a million mirrors that move independently of one another.
According to UCLA, in operation the automated mirrors create a pattern for each layer of the object being printed while the light cures the gel. At present, the printer uses four "bio-inks," but this number can be expanded.
So far, the printer has been used to create simple shapes, 3D simulations of muscle tissue and muscle-skeleton connective tissues, as well as fake tumors complete with blood vessels. In addition, the structures have been implanted in rats without being rejected.
"Tissues are wonderfully complex structures, so to engineer artificial versions of them that function properly, we have to recreate their complexity," says Khademhosseini. "Our new approach offers a way to build complex biocompatible structures made from different materials."
The research, which was funded by the Office of Naval Research and the National Institutes of Health, is published in Advanced Materials.
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