A Novel Two-Component, Expandable Bioadhesive for Exposed Defect Coverage: Applicability to Prenatal Procedures
Stefanie P. Lazow, MD1, Daniel F. Labuz, MD1, Benjamin R. Freedman, PhD2,3, Anna Rock, BS2, David Zurakowski, PhD1, David J. Mooney, PhD2,3, Dario O. Fauza, MD, PhD1
1Boston Children's Hospital, Boston, MA, 2Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, 3Harvard John A. Paulson School of Engineering and Applied Sciences at Harvard University, Cambridge, MA
Background: Prenatal coverage of congenital defects involves unique challenges, including defect expansion over time and continuous exposure to amniotic fluid. We sought to test whether a novel bioadhesive composite could overcome these obstacles.
Methods: New Zealand rabbit fetuses (n=23) underwent surgical creation of spina bifida on gestational day 22-25 (term 32-33 days). Defects were immediately covered with a two-component bioadhesive consisting of a hydrogel made of a double network of ionically crosslinked alginate and covalently crosslinked polyacrylamide linked to a bridging chitosan polymer adhesive (figure). Animals were euthanized prior to term for different analyses, including hydraulic pressure testing. Statistical comparisons were by Mann-Whitney U tests (p<0.05).
Results: Hydrogels remained adherent in 70% (16/23) of the recovered fetuses and in all of the last 14 fetuses, as the procedure was optimized. Adherent hydrogels showed a median two-fold (IQR:1.7-2.4) increase in area at euthanasia, with defect coverage further confirmed by histology and ultrasound (Figure). The median maximum pressure to repair failure, defined as leak/detachment or rupture, was 15mmHg (IQR:7.8-55.3). These pressures exceed reported neonatal cerebrospinal fluid pressures.
Conclusion: This novel bioadhesive composite allows for selective and stable attachment to specific areas of the spina bifida defect in a fetal rabbit model, while the hydrogel expands with the defect over time. It could become a valuable alternative for the prenatal repair of spina bifida and other congenital anomalies.
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