Chitosan-based nanofibers with an average fiber diameter controllable from a few microns down to similar to 40 nm and a narrow size distribution were fabricated by electrospinning solutions containing chitosan, polyethylene oxide (PEO), and Triton X-100 (TM). Rheological study showed a strong dependence of spinnability and fiber morphology on solution viscosity and thus on chitosan-to-PEO ratio. The nanofibers can be deposited either as a nonwoven mat or as a highly aligned bundle of controllable size. Potential use of this nanofibrous matrix for tissue engineering was studied by examining its integrity in water and cellular compatibility. It was found that the matrix with a chitosan/PEO ratio of 90/10 retained excellent integrity of the fibrous structure in water. Experimental results from cell stain assay and SEM imaging showed that the nanofibrous structure promoted the attachment of human osteoblasts and chondrocytes and maintained characteristic cell morphology and viability throughout the period of study. This nanofibrous matrix is of particular interest in tissue engineering for controlled drug release and tissue remodeling. (c) 2005 Elsevier Ltd. All rights reserved.