Tissue-engineered neocartilage with appropriate biomechanical properties holds promise not only for graft applications but also as a model system for controlled studies of chondrogenesis. Our objective in the present research study is to better understand the impact of fiber diameter on the cellular activity of chondrocytes cultured on nanofibrous matrices. By using the electrospinning process, fibrous scaffolds with fiber diameters ranging from 300 nm to 1 mu m were prepared and the physicomechanical properties of the scaffolds were characterized. Bovine articular chondrocytes were then seeded and maintained on the scaffolds for 7 and 14 days in culture. An upregulation in the gene expression of collagen II was noted with decreasing fiber diameters. For cells that were cultured on scaffolds with a mean fiber diameter of 300 nm, a 2-fold higher ratio of collagen II/collagen I was noted when compared to cells cultured on sponge-like scaffolds prepared by freeze drying and lyophilization. Integrin (alpha(5), alpha v, beta(1)) gene expression was also observed to be influenced by matrix morphology. Our combined results suggest that matrix geometry can regulate and promote the retention of the chondrocyte genotype. Copyright (C) 2011 S. Karger AG, Basel