Sunday, October 10, 2004

Bony Palatal Fusion Following In Utero Repair of the Congenital Cleft Palate Model

Jennifer S. Lee, MD, Albert Woo, MD, Kip Panter, PhD, John Seki, MD, Anthony Spangenberger, and Jeffrey Weinzweig, MD.

Introduction: Intrauterine cleft palate repair has been performed in our congenital caprine model with resultant scarless healing of the mucoperiosteal flaps. Despite single-layer repair of these flaps, cleft narrowing has been observed in all repaired palates. Partial bony palatal fusion has been observed in 37% of these cases. Other animal models have shown upregulation of growth factors upon fusion of the medial edge epithelium (MEE) between the mucoperiosteal flaps in nonclefted animals. We hypothesized that flap elevation and repair mimics fusion and stimulates production of bone morphogenetic protein (BMP) and transforming growth factor-β3 (TGF-β3). BMP and TGF-β3 would in turn promote osteogenesis and tissue remodeling across the repaired flaps, thus producing partial bony fusion and narrowing of the palate.

Methods: Fetal clefting was induced in time-dated pregnant goats by anabasine gavage during gestational days 32-42. Immunohistochemical localization of BMP and TGF-β3 was performed on harvested palates during gestational days: 30 (before gavage), 36, 40, 80, 90, and 100. A group of fetuses that had undergone palatoplasty at day 85 were harvested for similar assessment at days 90 and 100.

Results: Preliminary immunohistochemical analyses demonstrate increased BMP and TGF-β3 levels at the MEE in control nonclefted animals and in those following in utero repair.

Conclusion: Confirmation of these findings would support our hypothesis, providing a mechanism for the observed cleft narrowing and bony fusion following in utero repair and supporting the potential benefit of intrauterine intervention.

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