A NEW IN-UTERO SHEEP MODEL FOR UNILATERAL CORONAL CRANIOSYNOSTOSIS

Several animal models have been designed in the past to analyze the pa thophysiology and management of craniosynostosis, very few of which we re intrauterine. Those that were interuterine had problems with either a short gestation or limited availability that prevented most researc hers from using them in treatment analysis. We desired to create a bio logically sound intrauterine model of craniosynostosis, using an anima l with a long gestation and an early calvarial bone formation, which w as easy to manipulate in utero, that could be created by any researche r studying this disorder. Using biologic data available regarding grow th factors thought to be involved in bone growth and cranial suture cl osure, we developed a new in utero fetal lamb model for the study of c raniosynostosis. Ten 70-day gestation fetal lambs (term gestation 140 days) received a midline coronal incision to expose both coronal sutur es. The entire right coronal suture was then excised along with a 4-mm bony margin. In each animal, the site was packed with 25 mg of demine ralized sheep bone powder augmented with 50 mu g of bone morphogenetic protein-2 (BMP-2) and 1 mu g of poly-transforming growth factor-beta. The scalp was closed, and the sheep were returned to the uterus until either 90 or 140 days of gestation. Complete fusion of the right coro nal suture occurred in all fetuses by 90 days gestation. In every anim al, right-sided frontal bone flattening and supraorbital rim elevation were evident. Histologic analysis showed bony synostosis at the sutur e site without evidence of suture regeneration. By 140 days, this isol ated suture fusion led to marked craniofacial abnormalities including right supraorbital rim elevation, significant frontal bone flattening, a decrease in the anterior-posterior length of the cranial vault, and flattening of the cranial base. In conclusion, we have developed a ne w model for the study of the secondary effects induced by the process of cranial suture fusion, which produces abnormalities seen in natural ly occurring cases of isolated right coronal suture synostosis. In add ition, this model confirms that isolated coronal suture fusion alone c an lead to the multiple cranial and facial abnormalities seen with thi s disorder, even in the absence of associated cranial base suture fusi ons.