BOB Ped Surg 2023 - Christina Theodorou, CAPS - Presentation

Thank you for the opportunity to present our pilot study on the repair of diaphragmatic hernia in a rat model using a novel biodegradable polyurethane patch. We have no conflicts of interest to declare. The optimal management of congenital diaphragmatic hernia is an area of active research. In cases of large defects, diaphragmatic replacements are used, most commonly synthetic patches such as PTFE or Gore-Tex. However, these replacements are associated with significant morbidity including hernia recurrence, bowel obstructions, and chest wall deformities as the child grows. The ideal diaphragm replacement would integrate with native tissue, mechanically match the function of the diaphragm and allow for growth with the child. Our lab has collaborated with a bioengineering team in Texas, who are actively investigating the use of polyurethanes, or PU, which are elastomeric polymers. In particular, biodegradable forms of PU have been used in tissue repair recently such as vascular and muscular tissue replacement and have high mechanical strength. We tested the PU patch in a rat model comparing it to diaphragm repair with Gore-Tex. We hypothesized that this novel PU-based patch would be durable and would not result in recurrent herniation. Additionally, the elastic nature of the patch would allow for more diaphragmatic excursion than Gore-Tex. We created a surgical model of diaphragmatic defects in rats, creating 4 mm defects followed by immediate patch repair. Each cohort had six animals, as well as a sham cohort of six rats who underwent laparotomy without diaphragm defect creation or repair. After repair, animals were survived for four weeks with fluoroscopic evaluation of diaphragmatic excursion with respiration at one and four weeks post-op. At four weeks they were euthanized and dissected to evaluate for hernia recurrence and adhesions to the patch. H&E staining was also performed. No recurrences were seen in either cohort. At one week, there was no difference in diaphragmatic excursion between sham, Gore-Tex, and PU animals. At four weeks, Gore-Tex had limited diaphragm rise compared to sham, but no difference was found between PU and sham. There were no differences between PU and Gore-Tex at any time point. Moving on to the histology, an inflammatory capsule was formed surrounding both patches and there was no significant difference in the size of that inflammatory capsule between the cohorts. In conclusion, the novel PU patch was similar to Gore-Tex in its short-term durability with no recurrences at four weeks. The PU patch allowed for diaphragmatic excursion that better matched the sham cohort. Both patches formed surrounding inflammatory capsules. However, further work is needed to evaluate long-term functional outcomes and to further optimize the properties of the PU patch. There are several limitations to this small pilot study. We had small numbers of animals in each cohort, thus likely under powering us to detect significant differences. Additionally, the 4 mm defect size is small, and we are performing additional studies using larger defects. Longer-term follow-up will be important, as most recurrences occur at least a few months out from surgery, most commonly within the first two years. As the biodegradation rate of the PU patch can be altered, by performing serial studies over a variety of time points, we hope to match the degradation rate to the rate of tissue in growth with the goal of complete replacement over time with native diaphragm tissue. Thank you.