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Biomedical subjects

K Vanderwall

Publications and source records attributed to K Vanderwall.

6 recordsLinked to original sources
PubMed1998

Bone morphogenetic protein-2 induces scar formation and skin maturation in the second trimester fetus.

Fetal mammals heal skin wounds through the second trimester of development without evidence of scar. We have investigated the role of bone morphogenetic protein 2 (BMP-2), which is a member of the TGF-beta superfamily, in normal skin development and fetal wound healing. We first used RNA in situ hybridization to demonstrate that BMP-2 was expressed at low levels in the developing hair follicles and in the epidermis of normal human fetal skin. We then created an in vivo model to test how exogenous BMP-2 would affect fetal skin development and wound healing. Fifty micrograms of BMP-2 was implanted into the subcutis of five 70-day-old fetal lambs through a full-thickness linear incision. The BMP-2 was placed beneath the right half of the wound, whereas the left half served as an untreated control. In two of the five animals 1 microgram of TGF-beta was placed into the same position in addition to the 50 micrograms of BMP-2. Twenty days later (90 days gestation, term = 140 days) all the fetal wounds were examined for evidence of cellular hyperproliferation and scar formation. BMP-2 induced massive dermal and epidermal growth when compared with controls. This finding was characterized by marked epidermal thickening and keratinization, a dramatic increase in the number of hair follicles, and more than 50 percent thickening of the dermis. The dermal thickening was the result of both increased cellularity and deposition of large irregular collagen bundles. Wounds treated with both BMP-2 and TGF-beta healed also with an adult-like pattern of scar formation. Surprisingly, the wounds with BMP-2 alone healed with an equal pattern of scar, indicating that there was not an additive effect of combining BMP-2 and TGF-beta. We conclude that BMP-2 is a pleomorphic growth factor that induces cellular growth, maturation, and fibroplasia in both the dermis and epidermis. Further analysis of this growth factor in both fetal and adult wound healing may lead to important discoveries regarding the control of scar formation and fibrosis in many adult tissues.

Adult↗
PubMed1998

A new in utero sheep model for unilateral coronal craniosynostosis.

Several animal models have been designed in the past to analyze the pathophysiology and management of craniosynostosis, very few of which were intrauterine. Those that were interuterine had problems with either a short gestation or limited availability that prevented most researchers from using them in treatment analysis. We desired to create a biologically sound intrauterine model of craniosynostosis, using an animal with a long gestation and an early calvarial bone formation, which was easy to manipulate in utero, that could be created by any researcher studying this disorder. Using biologic data available regarding growth factors thought to be involved in bone growth and cranial suture closure, we developed a new in utero fetal lamb model for the study of craniosynostosis. Ten 70-day gestation fetal lambs (term gestation 140 days) received a midline coronal incision to expose both coronal sutures. 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 demineralized sheep bone powder augmented with 50 microg of bone morphogenetic protein-2 (BMP-2) and 1 microg 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 coronal suture occurred in all fetuses by 90 days gestation. In every animal, right-sided frontal bone flattening and supraorbital rim elevation were evident. Histologic analysis showed bony synostosis at the suture site without evidence of suture regeneration. By 140 days, this isolated 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 new model for the study of the secondary effects induced by the process of cranial suture fusion, which produces abnormalities seen in naturally occurring cases of isolated right coronal suture synostosis. In addition, this model confirms that isolated coronal suture fusion alone can lead to the multiple cranial and facial abnormalities seen with this disorder, even in the absence of associated cranial base suture fusions.

Animals↗
PubMed1998

The in utero correction of unilateral coronal craniosynostosis.

We performed the first in utero correction of a unilateral right coronal craniosynostosis using 70-day gestation fetal lambs. The craniosynostosis was created in eight fetuses by excising their right coronal sutures, and then placing demineralized bone powder, transforming growth factor-beta, and bone morphogenetic protein-2 into the defect. Twenty-one days later, after suture fusion had occurred, four of the eight sheep were treated with a 4 mm x 12 mm strip craniectomy to open the entire synostosed right coronal suture. The edges of the excision were wrapped with 100-microm-thick Gore-Tex (W. L. Gore & Associates, Flagstaff, Ariz.) sheets to prevent bony refusion. All eight lambs then progressed to term (140 days). The skulls of four normal, unoperated, term lambs were used as controls. At 140 days, all four treated lambs had a widely patent strip craniectomy site without any evidence of bone regeneration. This in utero correction led to a marked improvement in craniofacial morphology of three of four animals when compared with the uncorrected controls with significant (p < 0.01) correction in orbital position, skull length, and shape of the frontal bone. This was in sharp contrast to the uncorrected animals, which had marked orbital elevation, compression of the anteroposterior length of the cranial vault, frontal bone flattening, and shortening of the cranial base. The fourth corrected animal also showed evidence of improvement but had some abnormal calvarial changes secondary to the development of horns, which displaced the calvaria in a downward vector. We conclude that the in utero correction of craniosynostosis is feasible and provides a significant benefit by decreasing the severity of many of the associated deformities seen with this disorder.

Animals↗
PubMed1998

Adverse outcomes following endoscopic repair of a fetal cleft lip using an ovine model.

OBJECTIVE: The purpose of this study was to determine if endoscopic techniques could be used to repair an epithelialized lip cleft with accuracy and with an outcome comparable to fetuses treated through an open hysterotomy. INTERVENTIONS AND RESULTS: In contrast to previous open fetal cleft lip repairs in the same model, none of the five fetuses reported here had a good aesthetic result. Although there was no evidence of scar histologically, the edges of the lip were poorly approximated. The epithelial lining and underlying dermis of the wound margins were notably inverted. The orbicularis oris muscle, which had been reapproximated, appeared thin and hypoplastic. Most of the vermilion elements were poorly aligned, and in one animal, there was a complete dehiscence of the repair. CONCLUSIONS: In a more representative model of cleft lip that is not an acute lip wound, in utero endoscopic suture repair of the ovine lip gave a poor result using current technology. Only a meticulously performed, multilayered, open repair of a cleft appears to give a good cosmetic and functional outcome. Further studies to improve the endoscopic repair as our technology advances are therefore warranted.

Animals↗
PubMed1997

A new in utero model for lateral facial clefts.

The etiopathogenesis behind the formation of atypical craniofacial facial clefts remains unknown. To test the hypothesis that physical restricting forces such as amniotic bands can lead to the formation of these unusual clefts in the postorganogenesis period, we have modified a previously reported fetal lamb model of amniotic band syndrome to examine the effects of these bands on craniofacial development. Five 70-day gestation fetal lambs (term, 140 days) were exposed via a maternal hysterotomy. In each animal, an attempt was made to create a lateral craniofacial cleft by applying a 2-0 nylon suture as a constriction band to the growing face. The sutures were attached to either the zygomatic arch or the infraorbital rim externally and then looped circumferentially into the oral commissure. Each suture was positioned so as to create either a Tessier type 5 or a Tessier type 7 cleft. Four of five fetal lambs survived to term. Both types of lateral facial clefts were effectively produced using this model. In each group, the presence of an intraoral constriction band led to the formation of macrostomia, with an average 7.4-mm lateral displacement of the oral commissure. In addition to these soft tissue changes, each animal also had partial bony clefting (i.e., a bony groove) induced by the pressure of the restriction band across the growing facial skeleton. In the two lambs with the Tessier type 7 cleft, incomplete bony clefts developed across the zygomatic arch. In three animals with bands placed across the medial infraorbital rim, significant infraorbital and malar bony clefts formed similar to a classic Tessier type 5 facial cleft. No evidence of tissue necrosis, maceration, or ulceration was noted in any animal. These data present, for the first time, evidence that the constriction of craniofacial growth by external forces such as a swallowed amnionic band can lead to the development of lateral facial clefting involving both soft tissue and bony elements. These malformations are likely due to a combination of directly tethering normal tissue migration and an increase in local pressure, which produces cellular ischemia and apoptosis. Furthermore, our data demonstrate that these clefts can occur later in fetal development during a period of facial growth rather than during the period of primary facial morphogenesis.

Amniotic Band Syndrome↗