Project abstract: Microengineered osteons for bone tissue engineering Repair of load bearing bone defects remains a significant clinical problem. Often bone grafts are required for reconstructive skeletal procedures to aid fracture healing, bone fusion, implant integration and repair of skeletal defects, but the use of allograft bone is limited by a high failure rate. Tissue engineered constructs are promising substitutes. However, engineered tissues for bone repair are often limited by a lack of vascularity, the difficulty to engineer the complex bone microarchitecture and insufficient scaffold mechanical strength. We propose to use a multi-scale approach to bone tissue engineering that combines nanoscale molecular alignment, microengineered tissues and biomimetic bone scaffolds. We therefore aim to generate microengineered osteon-like units and to integrate the resulting structures within biomimetic scaffolds and to analyze the constructs in vitro and in vivo. This will result in mineralized vascular tissues with controlled architectures on a variety of functional and physiologically relevant scales. It is expected that this project will generate a new paradigm in bone tissue engineering by enabling the formation of complex microstructures such as osteon-like units with vascular channels within cortical bone.