The regenerative capabilities of articular cartilage are very limited when injured or damaged by aging, tissue engineering concepts and methodologies that employ biocompatible matrices or scaffolds have the potential to help repair defects in articular cartilage by generating histological and functional normal tissue by seeding cells in a biocompatible scaffold and then implanting the cell-material complex to repair chondral defects There is an impetus to design and develop scaffolds that mimic the native ECM of articular cartilage, and distribute strain in a bioresponsive manner to signal seeded chondrocytes to synthesize and organize ECM to result in material properties that are in range of natural cartilage. The long-term goal of our research is to generate tissue-engineered neocartilage with appropriate biomechanical properties, not only for graft applications, but also as a model system for controlled studies of chondrogenesis. The objective of this application is to design and develop scaffolds that closely approximate the native extracellular matrices (ECM) of articular cartilage, which are primarily composed of collagen nanofibers, and to evaluate the feasibility of these approaches within the paradigm of cartilage tissue engineering. The innovation in this project is our ability to reproducibly prepare porous scaffolds based on aligned nano- and/or submicron-range fibers with tunable biomechanical properties and substrate rigidity, and to evaluate the specific contributions of substrate mechanics, mechanical stress, and other physical factors on cellular activity in biomimetic matrices. We anticipate that tissue-engineering approaches with submicron- or nanofiber based scaffolds developed in this study will provide tools for an improved understanding of tissue development, by providing a combined study of histologic, biochemical, and mechanical property findings. The engineering methodology developed in this proposal may have broader impacts on the manufacturing of other surfaces for tissue engineering. [unreadable] [unreadable] [unreadable]