3D-printed ear, bone and muscle structures come to life after implantation in mice
3D printed tissues and organs have shown real potential in addressing shortages of available donor tissue for people in need of transplants, but having them take root and survive after implantation has proven difficult to achieve. In a positive move for the technology, researchers have used with a newly-developed 3D printer to produce human-scale muscle structures that matured into functional tissue after being implanted into animals.
Researchers have been exploring bioprinting as a means of replacing damaged tissue for several years now. The difficulty in replicating the complexities of human tissue has proven no simple undertaking, however, with scientists testing the waters with specialized bio-inks and various purpose-built printers in an effort to produce usable, engineered tissue.
Researchers at Wake Forest Baptist Medical Center have taken this latter path to engineering structures of adequate size and strength to implant in the human body. More than a decade in the making, the team's Integrated Tissue and Organ Printing System (ITOP) is claimed to overcome the limitations of previous bioprinting approaches. It spouts water-based gels that contain the cells, along with biodegradable polymers arranged in a latticed pattern and a temporary outer structure.
The water-based gels were optimized to promote cell growth and health. This, combined with micro-channels that allow nutrients and oxygen from the body to permeate the structure, allows the system to remain alive while it develops a system of blood vessels.
The researchers say that previously, engineered tissue structures without ready-made blood cells needed to be smaller than 200 microns in order for the cells to survive, but that their new approach solves this problem. They used ITOP to produce baby-sized ear structures measuring 1.5 in (3.8 cm) long, which were implanted under the skin of mice in the lab and went on to show signs of vascularization one and two months later.
To demonstrate its capabilities when it comes to soft tissue structures, the team used the system to produce muscle tissue, implanting it in rats and finding that two weeks later it was robust enough to vascularize and induce nerve formation. Using human stem cells, the system also printed jaw bone fragment large enough for a facial reconstruction and implanted them in rats. Five months later, the structures had matured into vascularized bone tissue.
"Our results indicate that the bio-ink combination we used, combined with the micro-channels, provides the right environment to keep the cells alive and to support cell and tissue growth," says Anthony Atala, senior author on the study.
Further adding to ITOP's potential is its ability to take data from CT or MRI scans and make bespoke tissue for patients. So if a patients is missing a particular piece of tissue, such as a section of ear or nose, for example, the system could reproduce a precise replica.
"This novel tissue and organ printer is an important advance in our quest to make replacement tissue for patients," says Anthony Atala, senior author on the study. "It can fabricate stable, human-scale tissue of any shape. With further development, this technology could potentially be used to print living tissue and organ structures for surgical implantation."
The researchers will continue to explore the approach to track longer term results. Their current study is published in the journal Nature Biotechnology.