Grants We Funded

Abstract
The role of chondrocyte biology in the development and treatment of craniofacial disorders remains largely unstudied. Current advances in both genetic and bioengineering have significant potential for the field of craniofacial and pediatric plastic surgery. Recent studies indicate that the genetic sex of a cell has fundamental consequences for the success of certain cell therapy strategies (l). Dr. Boyan's group has shown that chondrocytes from male and female rats respond to estrogen and testosterone in distinctly different ways, although both sexes possess receptors for both hormones. Her group has now shown that human chrondrocytes also exhibit sexual dimorphism in their responses to 17-beta estradiol (2). A study from another group showed that male predominance in metopic and sagittal craniosynostosis and in nonsynostotic plagiocephaly, suggesting a role for circulating androgens in early craniofacial development skeleton (3). Based on these observations we would like to investigate the role of sexual dimorphism in chondrocyte differentiation in vitro and in vivo. My overall goal is to develop a method for reproducible and effective delivery of cells for tissue regeneration and repair. I will use an alginate microencapsulation method developed in Dr. Boyan's lab to produce microcapsules 150-180 microns in diameter containing approximately 80 chondrocytes each. These microcapsules are small enough to permit percutaneous delivery using a standard gauge needle; they permit rapid diffusion of nutrients; and cell viability and phenotype expression are preserved. I will assess whether there is a difference in the behavior of male and female chondrocytes with respect to their response to 17- beta-estradiol and 5-hydroxytestosterone when encapsulated, and to circulating hormones when implanted in same or opposite sex mice. We will use nude mouse model muscle as a site for implantation and will analyze the quality and quantity of the cartilage produced by histomorphometric techniques. The last part of this study will be to determine if sexual dimorphism extends to responses of cells to growth factors typically used in cartilage tissue engineering: TGF-beta-l and 3, IGF-l, and PDGF-BB. In vitro studies (dose response and time course) will indicate if male and female cells exhibit differences in phenotypic expression or matrix synthesis. Based on these results, we will pretreat microencapsulated chondrocytes and then assess chondrogenesis in vivo using similar techniques. Since cartilage and soft tissue defects extend not only to craniofacial disorders but also to the trauma and aging population, the ability to expand a patient's own cartilage or mesenchymal stem cells using a micro-delivery system would have a plethora of applications in the field of plastic surgery. Such a delivery system could be applied to fat or muscle injection as well.