Hydrogel protection: a novel approach to reduce bowel inflammation in experimental gastroschisis.
OBJECTIVE
In gastroschisis there is herniation of the fetal bowel into the amniotic cavity that results in severe intestinal dysfunction. In order to reduce bowel exposure to amniotic fluid we used a hydrogel of N-isopropylacrylamide copolymerized with acrylic acid (P(NIPAAm-co-AAc)) to coat the herniated bowel through the use of a fibrin adhesive (Beriplast).


METHODS
Gastroschisis was created in fetuses of 31 pregnant Sprague-Dawley rats by evisceration of the bowel through a right paramedian incision in the abdominal wall on day 18.5 of pregnancy. The fetuses were separated in four groups of 12 fetuses: control (C), gastroschisis (G), gastroschisis+fibrin adhesive (GA) and gastroschisis+fibrin adhesive+dry hydrogel (GAH). Animals were harvested at day 21.5 of pregnancy and the hydrogel was removed. Fetuses and bowels were weighed and morphometric analysis was performed. Isoelectric focusing of the amniotic fluid determined its electrical charge. We evaluated the hydrogel swelling ratio (Q) in the amniotic fluid. Histological analysis and scanning electronic microscopy (SEM) of the bowel and hydrogel were performed. Our primary outcome was bowel intactness after hydrogel removal and our secondary outcome was the effectiveness of the hydrogel in protecting the bowel against amniotic fluid and its components. Differences among the groups were tested by the ANOVA and Tukey-Kramer post-test method and the statistical significance accepted was for p values <0.05.


RESULTS
The mass of swollen hydrogel was 34 times the mass of dry hydrogel. Isoelectric focusing of the amniotic fluid showed that most of its proteins are negatively charged as the hydrogel. SEM showed that removal of the hydrogel did not damage bowel serosa. Bowel weight, diameter and wall thickness were similar between groups C and GAH but bowel diameter and wall thickness was significantly reduced in C and GAH compared to G and GA (p<0.001).


CONCLUSIONS
The P(NIPAAm-co-AAc) hydrogel does not harm the bowel and provides a safe effective protection with reduction of bowel damage in gastroschisis.
Gonçalves
Frances Lilian Lanhellas
FL
Division of Pediatric Surgery, Department of Surgery, School of Medical Sciences, University of Campinas, UNICAMP, CP 6111, Campinas, SP, Brazil.
da Silva
Regiane
R
Schmidt
Augusto Frederico
AF
de Oliveira
Marcelo Ganzarolli
MG
Sbragia
Lourenço
L
D000178:Acrylamides / Q000627:therapeutic use*; D000653:Amniotic Fluid / Q000737:chemistry; D000818:Animals; D005260:Female; D015718:Fibrin Tissue Adhesive / Q000627:therapeutic use; D020139:Gastroschisis / Q000150:complications* / Q000188:drug therapy*; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000627:therapeutic use*; D007249:Inflammation / Q000517:prevention & control*; D007422:Intestines / Q000002:abnormalities; D007525:Isoelectric Focusing; D008855:Microscopy, Electron, Scanning; D023421:Models, Animal; D011108:Polymers / Q000627:therapeutic use*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley
D000178:Acrylamides; D015718:Fibrin Tissue Adhesive; C090629:N-isopropylacrylamide-acrylic acid copolymer; D011108:Polymers; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate