Determining the Differential Effects of Stretch and Growth in Tissue-Expanded Skin: Combining Isogeometric Analysis and Continuum Mechanics in a Porcine Model.

BACKGROUND: The relative effects of skin growth and stretch during tissue expansion have not been studied. The authors use novel analytic techniques that allow calculation of these factors at any point of a skin patch. OBJECTIVE: The authors sought to determine how stretch and growth change with different expansion rates and to correlate these values with histologic and cellular changes in skin. MATERIALS AND METHODS: Two minipigs were implanted with a total of 5 tissue expanders under tattooed skin grids. One pig was expanded over 35 days and the second over 15 days. Isogeometric analysis allowed calculation of growth and stretch. Expanders with similar total deformation were compared between protocols. Regression analysis determined predictive effects of stretch and growth on histologic data from the second animal. RESULTS: Deformation was more attributable to stretch in rapid than in slow expansion (1.40 vs1.12, p < .001). Growth was higher in slow expansion than in rapid (1.52 vs 1.07, p < .001). Both growth and stretch predicted epidermal thickness, dermal thinning, and keratinocyte proliferation. Growth predicted vascularity. CONCLUSION: Isogeometric analysis allows determination of precise surface area changes for correlation to microscopic-level data. Using the model, the authors identified that skin deformation in rapid expansion is more attributable to stretch.

The Morphogenesis of Cranial Sutures in Zebrafish.

Using morphological, histological, and TEM analyses of the cranium, we provide a detailed description of bone and suture growth in zebrafish. Based on expression patterns and localization, we identified osteoblasts at different degrees of maturation. Our data confirm that, unlike in humans, zebrafish cranial sutures maintain lifelong patency to sustain skull growth. The cranial vault develops in a coordinated manner resulting in a structure that protects the brain. The zebrafish cranial roof parallels that of higher vertebrates and contains five major bones: one pair of frontal bones, one pair of parietal bones, and the supraoccipital bone. Parietal and frontal bones are formed by intramembranous ossification within a layer of mesenchyme positioned between the dermal mesenchyme and meninges surrounding the brain. The supraoccipital bone has an endochondral origin. Cranial bones are separated by connective tissue with a distinctive architecture of osteogenic cells and collagen fibrils. Here we show RNA in situ hybridization for col1a1a, col2a1a, col10a1, bglap/osteocalcin, fgfr1a, fgfr1b, fgfr2, fgfr3, foxq1, twist2, twist3, runx2a, runx2b, sp7/osterix, and spp1/ osteopontin, indicating that the expression of genes involved in suture development in mammals is preserved in zebrafish. We also present methods for examining the cranium and its sutures, which permit the study of the mechanisms involved in suture patency as well as their pathological obliteration. The model we develop has implications for the study of human disorders, including craniosynostosis, which affects 1 in 2,500 live births.