(From the January 2014 issue of Research Now)
Tissue-engineered intestine could provide a permanent fix to a potentially fatal condition called short bowel syndrome, which affects many premature infants following surgery to treat necrotizing enterocolitis. Scientists in The Research Institute at Nationwide Children’s are making progress toward identifying a material for the scaffold that the body won’t reject and that will enable the replacement tissue to perform each of the intestine’s many functions. The work was reported in a recent issue of the Journal of Biomedical Materials Research.
For the study, a team led by Gail E. Besner, MD, chief of pediatric surgery and principal investigator in the Center for Perinatal Research, examined seven scaffold materials in search of one with the biodegradability, biocompatibility, strength and elasticity needed for safe implantation and proper function in the human body. They identified two leading candidates—known as PGA and PDLGA polymer materials—that have many of the necessary characteristics upon which replacement intestine can be built.
By using biodegradable materials to support the growth of a patient’s own cells, a tissue-engineered intestine scaffold will gradually dissolve as new human tissue replaces it. The challenge lies in finding a material that degrades at the right speed without eliciting a strong immune response. PGA and PDLGA both have desirable biocompatibility and degradation outcomes.
“So far, these materials seem to be good options,” says Dr. Besner, who also is a professor of surgery and pediatrics at The Ohio State University College of Medicine. “But we need to keep improving the design and exploring other materials to make sure that when tissue-engineered intestine makes it to clinical trials in humans, we have everything right—from the thickness of the fibers themselves to the amount of open space between the fibers in which cells can grow.”
Short bowel syndrome, the condition Dr. Besner’s lab hopes to treat with the tissue-engineered intestinal implants, results in severe malabsorption of nutrients and is often caused by surgical removal of large sections of the small bowel due to a variety of severe conditions affecting the gut.
Current treatments for short bowel syndrome are suboptimal and may entail long-term nutritional support, intestinal transplantation, repeat surgeries or other therapies with high complication rates and short-term effectiveness. In severe cases, the syndrome and its treatments may lead to end-stage liver disease or fatal malnutrition. Estimates of the fatality rate of short bowel syndrome among infants approach 40 percent.
“A treatment that could increase the length of the small intestine available to absorb nutrients could offer these patients a permanent cure and spare them from lifelong parenteral nutrition,” says Dr. Besner. “And if we can construct a new segment of intestine with the patient’s own cells, instead of transplanting tissue from other individuals, we could also help patients avoid lifelong immunosuppression.”
Similar tissue-engineering work has already been done with blood vessels and tracheas, both of which are currently in human trials. A tissue-engineered intestine, however, would need to perform both nutrient absorption and food transport in a non-sterile environment—challenges that other tissue-engineered body parts have not had to overcome.
“Advancements in the area of tissue engineering come gradually,” says Dr. Besner, who has been working on the concept for the past several years and anticipates that it may be several more years before the scaffolds are ready for human trials. “It’s a continuous process of research and improvement. We want the best possible product before we test this in humans.”
The team’s next step will be to seed intestinal stem cells onto the engineered intestinal scaffolds and subject them to a series of tests similar to those performed in this study. They plan to improve the design of the scaffold and connect it to functioning intestine in an animal model of short bowel syndrome in 2014.
“The implant needs to function just like healthy, native intestine,” says Dr. Besner. “It’s a very challenging process, but the potential reward for short bowel syndrome patients is enormous.”
The team’s latest publication results from a collaborative project with bioengineering experts at The Ohio State University and an Ohio start-up company called Nanofiber Solutions, LLC, which works with the researchers to construct the scaffolds according to their specifications. The groups received multiple awards for technology development in 2013 to continue improving the scaffolds for eventual use in patients.
Boomer L, Liu Y, Mahler N, Johnson J, Zak K, Nelson T, Lannutti J, Besner GE. Scaffolding for challenging environments: materials selection for tissue engineered intestine. Journal of Biomedical Materials Research. 2013 Nov 28. [Epub ahead of print.]