Tissue-Engineered, Three-Dimensional Human Dermis to Study Extracellular Matrix Formation in Wound Healing

Abstract

AbstractA human dermal model consisting of neonatal dermal fibroblasts grown on nylon mesh was used to study extracellular matrix (ECM) formation. The fibroblasts deposit ECM, forming a three-dimensional, tissue-like structure consisting of collagen types I and III, fibronectin, tenascin, and decorin. This model was compared with fetal, neonatal, and adult human dermis and was found to be most similar to fetal dermis.To determine keratinocyte-mediated effects on the dermal ECM, the dermal model was cocultured with human neonatal foreskin keratinocytes. Fibronectin synthesis and deposition were examined by in situ hybridization and indirect immunofluorescence, respectively. After 2 weeks, fibronectin deposition throughout the dermis had increased compared with dermal cultures incubated in the absence of keratinocytes, indicating that keratinocytes influenced net fibronectin deposition. As measured by in situ hybridization, fibronectin mRNA increased after coculture with keratinocytes, with maximal signal d...