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Delayed in Utero Repair of Surgically Created Fetal Cleft Lip and Palate

Abstract:

To properly evaluate the potential benefits of in utero repair for cleft lip and palate, an animal model of cleft lip and palate formation is needed that simulates human cleft morphology. We have developed a fetal lamb model in which incisional or excisional unilateral cleft lips were created early in gestation and later repaired. Through a maternal celiotomy and hysterotomy, six excisional and six incisional clefts were created in early first trimester fetal lambs. Clefts were created by a novel "space helmet" technique and made completely through the lip and the alveolus. Two weeks later, the wound edges were freshened and repaired in all but one lamb in each group. In the early third trimester, the fetuses were harvested and studied. We found that the incisional clefts healed spontaneously with replacement of the native reticular collagen pattern and with regeneration of the skin appendages. However, the excisional clefts did not autorepair and, when repaired surgically, healed without a collagen scar but showed no regeneration of the skin appendages. This preliminary study is the first successful large animal model where cleft lips and palates were created, allowed to develop with the cleft, and later repaired in utero. Prior to repair, the edges of the excisional clefts epithelialize. When repaired early in the third trimester, excisional clefts heal without a dermal scar but exhibit incomplete regeneration of the skin appendages.