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

在美国，每年发生600万例骨折，其中5-10%的骨折由于骨质流失、固定失败、感染和血管化不足而无法充分愈合。利用人体的优势来促进骨骼再生的生物材料的使用？患者自身的自然愈合能力将绕过所有与自体和同种异体移植相关的问题。为修复和再生大型骨缺损而开发骨科植入物的关键挑战是在材料特性、植入物结构和生物活性之间取得适当的平衡，以满足骨组织的功能和再生需求。澳大利亚悉尼大学的Hala Zreiqat博士和Roohani-Esfahani博士在实现这一目标方面取得了重大进展，他们开发了一种新的多组分陶瓷，可以模仿骨骼的孔隙度（80-95%）、孔径（300-500um）和独特的机械强度。这些支架可在兔桡骨缺损中形成广泛的新骨并完全桥接。然而，将生物材料植入损伤骨会影响炎症反应细胞的行为，尤其是巨噬细胞，从而影响新骨的再生。本课题的主要研究重点是巨噬细胞的行为如何决定组织再生。鉴于巨噬细胞和炎症反应对所有组织修复的重要性，本工作的结果广泛适用于任何组织的工程。此外，该项目将促进美国和澳大利亚工程专业学生和教师之间的跨文化交流。这个项目的五位参与者中有三位是女工程师。

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.