Surgeons at Boston Children’s Hospital have long sought a better solution for long-gap esophageal atresia, a rare birth defect in which part of the esophagus is missing. The current state-of-the art operation, called the Foker process, uses sutures anchored to children’s backs to gradually pull the unjoined ends of esophagus until they’re long enough to be stitched together. To keep the esophagus from tearing, children must be paralyzed in a medically induced coma, on mechanical ventilation, for one to four weeks. The lengthy ICU care means high costs, and the long period of immobilization can cause complications like bone fractures and blood clots.
Now, a Boston Children’s Hospital team has created an implantable robot that could lengthen the esophagus — and potentially other tubular organs like the intestine — while the child remains awake and mobile. As described today in Science Robotics, the device is attached only to the tissue being lengthened, so wouldn’t impede a child’s movement.
Lengthening the esophagus, robotically
The motorized, programmable device, covered with a smooth, waterproof “skin,” has two rings that are placed around the tissue and sutured firmly into place. A control unit outside the body applies adjustable traction forces to the rings, slowly and steadily pulling the tissue in the desired direction. Tested a large animal model, it stimulated the esophagus to regenerate while the animals went about their business, showing no apparent discomfort. They were even able to continue eating.
“This project demonstrates proof-of-concept that miniature robots can induce organ growth inside a living being for repair or replacement, while avoiding the sedation and paralysis currently required for the most difficult cases of esophageal atresia,” says Russell Jennings, MD, surgical director of the Esophageal and Airway Treatment Center at Boston Children’s and a co-investigator on the study.
Spurring tissue regeneration
Dupont and colleagues tested the device in five pigs, programming the two rings to pull in opposite directions. The distance between the two rings increased by 2.5-millimeter increments each day for 8 to 9 days.
On day 10, the segment of esophagus being lengthened had grown by an average of 77 percent. (Three untreated animals that served as controls had no such growth.) The esophagus maintained its normal diameter, and histologic examination of the tissue showed a proliferation of the cells that make up the esophagus.
“This shows we didn’t simply stretch the esophagus — it lengthened through cell growth,” says project leader Pierre Dupont, PhD, the study’s senior investigator and chief of Pediatric Cardiac Bioengineering at Boston Children’s.
Lengthening a short bowel?
The team is now starting to test the robotic system in a large animal model of short bowel syndrome — another debilitating condition that can be caused by necrotizing enterocolitis in the newborn, Crohn’s disease and various conditions requiring removal of part of the intestine.
“Short bowel syndrome is a devastating illness frequently requiring patients to be fed intravenously,” says gastroenterologist Peter Ngo, MD, a coauthor on the study. “This, in turn, can lead to liver failure, sometimes requiring a multivisceral (liver-intestine) transplant, an outcome that can be both devastating and costly.”
While long-gap esophageal atresia is extremely rare, short bowel syndrome is much more common. So it could prove to be the “killer app” that attracts industry interest. The team hopes to get support to continue testing the device in large animal models, and eventually conduct clinical trials. They will also test other features.
“No one knows the best amount of force to apply to an organ to induce growth,” explains Dupont. “Today, in fact, we don’t even know what forces we are applying clinically. It’s all based on surgeon experience. A robotic device can figure out the best forces to apply and then apply those forces precisely.”
The fine print
The study was supported by the Translational Research Program and Manton Center for Orphan Disease Research at Boston Children’s Hospital and by the Swiss National Science Foundation.
Dana Damian, PhD and Karl Price, MaSC in Dupont’s lab were co-first authors on the paper. Damian currently directs the Sheffield Biomedical Robotics Laboratory at the University of Sheffield and Centre of Assistive Technology and Connected Healthcare.
Coauthors were Slava Arabagi (Helbling Precision Engineering, Cambridge, MA); Ignacio Berra (National Pediatric Hospital J.P. Garrahan, Buenos Aires); Zurab Machaidze, Gustavo Arnal, David Van Story and Jeffrey D. Goldsmith (Boston Children’s); Sunil Manjila (McLaren Bay Neurosurgery Associates, Bay City, MI); Shogo Shimada (University of Tokyo Hospital); Assunta Fabozzo (The Hospital of Padua, Italy); Agoston T. Agoston (Brigham and Women’s Hospital); Chunwoo Kim (Korea Institute of Science and Technology, Seoul); and Russell Jennings, MD, Peter Ngo, MD, and Michael Manfredi, MD, of Boston Children’s.