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Background: Fetal tracheal occlusion (TO) is an experimental therapeutic approach to stimulate lung growth in the most severe congenital diaphragmatic hernia (CDH) cases. We have previously demonstrated a heterogeneous response of normal fetal rabbit lungs after TO with the appearance of at least two distinct zones. The aim of this study was to examine the fetal lung response after TO in a left CDH fetal rabbit model., Methods: Fetal rabbits at 25 d gestation underwent surgical creation of CDH followed by TO at 27 d and harvest on day 30. Morphometric analysis, global metabolomics, and fluorescence lifetime imaging microscopy (FLIM) were performed to evaluate structural and metabolic changes in control, CDH, and CDH + TO lungs., Results: Right and left lungs were different at the baseline and had a heterogeneous pulmonary growth response in CDH and after TO. The relative percent growth of the right lungs in CDH + TO was higher than the left lungs. Morphometric analyses revealed heterogeneous tissue-to-airspace ratios, in addition to size and number of airspaces within and between the lungs in the different groups. Global metabolomics demonstrated a slower rate of metabolism in the CDH group with the left lungs being less metabolically active. TO stimulated metabolic activity in both lungs to different degrees. FLIM analysis demonstrated local heterogeneity in glycolysis, oxidative phosphorylation (OXPHOS), and FLIM "lipid-surfactant" signal within and between the right and left lungs in all groups., Conclusions: We demonstrate that TO leads to a heterogeneous morphologic and metabolic response within and between the right and left lungs in a left CDH rabbit model., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Current therapeutic materials for spina bifida repair showed a limited number of options in the market, and none of them have all the requirements as the ideal patch. In fact, sometimes the surgical procedures pose substantial challenges using different patches to fully cover the spina bifida lesion. For this purpose, a tailored patch made of poly (L-lactic acid) and poly (ε-caprolactone) blend was designed and validated in vitro to accomplish all these requirements but was never tested in vivo., Material and Methods: In our present study, the designed patch was analyzed in terms of rejection from the animal when implanted subcutaneously and as a dural substitute in the spinal cord. Inflammatory reaction (Iba1), astrogliosis (GFAP), was analyzed and functional interaction with spinal cord tissue assessing the (%motor-evoked potentials /compound motor action potential) by electrophysiology., Results: No evidence of adverse or inflammatory reactions was observed in both models of subcutaneous implantation, neither in the neural tissue as a dural substitute. No signs of astrogliosis in the neural tissue were observed, and no functional alteration with improvement of the motor-evoked potential's amplitude was detected after 4 wk of implantation as a dural substitute in the rat spinal cord., Conclusions: Designed patch used as a dural substitute will apparently not produce inflammation, scar formation, or tethering cord and not induce any adverse effect on regular functions of the spinal cord. Further studies are needed to evaluate potential improvements of this novel polymeric patch in the spinal cord regeneration using spina bifida models., (Copyright © 2019. Published by Elsevier Inc.)

Background: Fetal tracheal occlusion (TO) is an emerging surgical therapy in congenital diaphragmatic hernia that improves the fetal lung growth. Different animal models of congenital diaphragmatic hernia and TO present advantages and disadvantages regarding ethical issues, cost, surgical difficulty, size, survival rates, and available genetic tools. We developed a minimally invasive murine transuterine TO model, which will be useful in defining how TO impacts lung molecular biology, cellular processes, and overall lung physiology., Materials and Methods: Time-mated C57BL/6 mice underwent laparotomy at embryonic day 16.5 (E16.5) with transuterine TO performed on two fetuses in each uterine horn. At E18.5, dams were sacrificed and fetuses harvested. The lungs of the TO fetuses were compared with the nonmanipulated counterparts by morphometric and histologic analysis., Results: Successful TO was confirmed in 16 of 20 TO fetuses. Twelve of them survived to E18.5 (75%). Fetal weights were comparable, but lung weights were significantly greater in TO (28.41 ± 5.87 versus 23.38 ± 3.09, P = 0.043). Lung to body weight ratio was also greater (0.26 ± 0.003 versus 0.22 ± 0.002, P = 0.006). E18.5 TO lungs demonstrated dilated central and distal airspaces with increased cellularity. DNA/protein and DNA/lung weight ratios were elevated while protein/lung weight ratio was lower in TO compared to control., Conclusions: Mice fetal transuterine TO is feasible with comparable outcomes to other current animal models. The increase in the lung weight, lung to body weight ratio and the DNA/protein ratio indicate organized lung growth rather than edema or cell hypertrophy., (Copyright © 2018 Elsevier Inc. All rights reserved.)