In Utero Models of Craniofacial Surgery

Abstract

Fetal surgery is finding ever-increasing applications. At present, fetal surgical techniques are used only to treat diseases associated with high mortality risk or severe morbidity if left untreated prior to birth. Yet as a discipline, in utero therapy is attractive to plastic surgeons because it affords the potential to (1) provide a scarless repair, (2) correct the primary deformity, (3) prevent secondary deformities, and (4) give the parents a "normal"-appearing child at birth. Each of these potential benefits is particularly important in patients with craniofacial anomalies. This article will both review the animal models that have been used to study the potential for intrauterine plastic surgery and provide a synopsis of the benefits that fetal therapy may provide in the treatment of selected craniofacial anomalies.

Toward Microsurgical Correction of Cleft Lip Ex Utero through Restoration of Craniofacial Developmental Programs

“…CL/P has dramatic consequences for the affected child and their family, requiring many cycles of surgery, speech therapy, specialized orthodontics, and dentistry [2,4,6,7]. Despite multiple interventions, patients with CL/P are often left with significant sequelae including visible scars, abnormal dentition, nasal deformity, lack of mid-facial growth as well as hyper-nasal speech, all of which can significantly impact patients’ future life and associated health care costs.…”

“…Presently, no single genetic lesion has been identified as a universal culprit for CL/P but it is understood that both genetic and environmental factors contribute to its etiology [2,3,5]. Murine models of clefting have been widely used based upon the fact that mice and humans share similar craniofacial developmental process [3,4] Genes encoding secreted growth factors and their receptors (such as the Tgf- β eta [24,25] /Bmp superfamily [12,26], Fgf [27], Shh [4,28] and their effectors, Wnt and Lef [29]) have been shown to be essential for the normal development of head and face structures in mice.…”

“…The possibility for intrauterine correction of CL/P would take advantage of the fact that fetal wound healing is phenotypically superior than adult or neonatal wound healing [2,3,4] and thus fetal CL/P surgery is an attractive surgical option [32,33]. In support of this approach, several groups have used intrauterine repair as a way to prevent scarless healing [2,34].…”

“…In support of this approach, several groups have used intrauterine repair as a way to prevent scarless healing [2,34]. Even though fetal surgical interventions for CLP have been performed and relevant surgical techniques have improved over the past 30 years, there are still limitations and feto-maternal risks during fetal surgical procedure [34].…”

“…These malformations result in facial disfigurement, impaired feeding and defective speech and create psychological, emotional and economic hardships for patients and their families [2]. Proper treatment of this deformity requires a multidisciplinary team consisting of pediatricians, plastic surgeons, geneticists, neurosurgeons, otolaryngologists, dentists, audiologists, speech-language pathologists, and psychologists [1,2]. …”