US-Australia Collaborative Research: Research Planning and proof-of-concept study of macrophage-scaffold interactions

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In the United States, 6 million bone fractures occur annually, and 5-10% of these fractures fail to heal adequately due to bone loss, failed fixation, infection, and inadequate vascularization. The use of biomaterials that can promote bone regeneration by taking advantage of the body?s own natural healing ability would bypass all of the problems associated with autografts and allografts. The key challenge in developing orthopedic implants for the repair and regeneration of large bone defects in load-bearing applications is to strike the right balance between material properties, implant architecture and bioactivity to satisfy the functional and regenerative requirements of bone tissue. Dr. Hala Zreiqat and Dr. Roohani-Esfahani at the University of Sydney in Australia have made major advances towards achieving this goal through the development of a new multi-component ceramic that can mimic bone in porosity (80-95%), pore diameter (300-500um) and, uniquely, mechanical strength. These scaffolds caused extensive new bone formation with complete bridging of critically sized radial defects in rabbits. However, implantation of biomaterials into injured bone affects the behavior of the cells of the inflammatory response, especially macrophages, with resulting effects on new bone regeneration. The main research focus of this proposal is how the behavior of macrophages dictates tissue regeneration.Given the importance of macrophages and the inflammatory response for the repair of all tissues, the results of this work are broadly applicable for engineering of any tissue. In addition, this project will promote cross-cultural exchange between American and Australian engineering students and faculty. Three of the five participants in this project are women engineers.