Grants Funded

Abstract
Project Summary: Outer-ear malformations affect roughly 1/6,000 newborns. Correction of external auditory deformities through non-surgical molding has been successful if started within the first week of life. After 3 weeks, the success of molding drops significantly and requires a longer splinting period. Thus, otoplasty remains the most reliable solution for external ear deformities beyond the first week of life, but the procedure is not performed until the ear is fully developed, about 6 to 7 years. Early neonatal cartilage plasticity is thought to be driving force behind nonsurgical correction of external ear deformities. It has been hypothesized in the literature that circulating maternal estrogen contributes to early plasticity via increasing expression of hyaluronic acid, decreasing elasticity and increasing cartilage malleability. While this mechanism has yet to be studied in sufficient detail, it suggests a potential for use of estrogen to re-establish neonatal cartilage plasticity and improve the success of non-surgical cartilage reencountering after the first week of life. Our preliminary data demonstrates a positive effect of local estrogen injections, resulting in the ability to alter and maintain the shape of an adult rabbit ear in response to splinting. We propose to confirm the lasting effect and mechanism of local estrogen treatment on ear molding and evaluate the utility of a more clinically relevant topical formulation. We will use our established model of New Zealand white rabbits with large ears similar in character to adult human ears. The rabbits will be randomized into 1 of 4 groups with both ears receiving the same treatment. The treatment groups will be 1) local estrogen injection; 2) local saline injection; 3) EstroGel®, topical estrogen; and 4) untreated controls. The ears will be folded and splinted for 4 weeks during treatment. The splints will be removed at 4 weeks and the long-term ear morphology will be documented for 4 additional weeks. Histologic changes to the cartilage structure and thickness will be assessed comparing the treatment and control groups. The ability to alter the plasticity of auricular cartilage will have broad implications for the treatment of congenital and oncologic deformities of the face. Noninvasive ear contouring will address many disadvantages of current surgical methods including risk, pain, recurrence, cost, and delay of surgical treatment for malformations of the external ear. Impact Statement: Congenital ear malformations cause anxiety, lowered self-esteem, and distress to children and their parents. Beyond early infancy, most malformations can only be corrected surgically. Surgical treatment has potential complications, is expensive, and must wait until nearly school age to be performed. Many malformations can be corrected by noninvasive external molding early in infancy. Maternal estrogen is thought to be the reason for this difference but this mechanism has not been explored. We aim to establish whether exogenous estrogen is able to rejuvenate the adult ear to behave and mold like the infant ear. Furthermore, we aim to evaluate the changes in ear cartilage at the microscopic level in response to estrogen to fully test the hypothesis.

Biography
Jonathan S. Black, MD, FACS, FAAP (Principal Investigator) <br /> Dr. Black is a pediatric plastic surgeon who received his BS and MD from the University of Nebraska. He completed residency in Plastic Surgery at the University of Virginia and fellowship training in Craniofacial Surgery at the Medical College of Wisconsin. Upon completion of training, Dr. Black accepted a position as Assistant Professor of Plastic Surgery at the University of Virginia in 2014. His clinical focus is on the care of patients with both congenital and acquired craniofacial deformities, including deformities of the ear. He performs corrective surgery for prominent ear, cryptotia, constricted ear, and ear defects from trauma and cancer. Routinely, Dr. Black treats infants with ear malformations using noninvasive molding and would like to offer this treatment modality beyond the period of early infancy. His primary research interest is altering the plasticity of cartilage to make this a reality. He works directly with Patrick Cottler, PhD (Co-Investigator) to perform the preliminary work using estrogen to alter the malleability of ear cartilage through external splinting and have seen promising results. The ultimate goal is to obtain a reliable nonsurgical alternative for ear deformities for the children who are currently treated only with surgery.