Laboratory equipment for the study of periprosthetic osteolysis

全关节置换术，即完全人工置换自然关节（特别是髋关节和膝关节），是一种通常能减轻疼痛和恢复关节功能的外科手术。2003年，加拿大进行了超过50,000例髋关节和膝关节置换术，其中35%的患者年龄小于65岁。随着预期寿命的增加，需要延长假体的生存期，以避免复杂的翻修手术及其相关的发病率和死亡率。全关节置换术失败的主要原因之一是假体周围骨破坏引起的无菌性松动（假体周围骨溶解）。磨损颗粒已被证明通过刺激周围细胞，导致炎症介质的释放，在很大程度上参与了假体周围骨溶解的诱导。本研究的目的是通过分析细胞对磨损颗粒的反应来确定假体周围骨溶解的生物学机制，并通过专门针对这些细胞和机制设计的工程纳米球来调节这种细胞反应和分子机制。需要层流工作站、双细胞培养室和超低温冷冻室进行细胞培养，并在低温下保存细胞和组织样品。需要实时PCR系统来分析暴露于磨损颗粒的巨噬细胞的基因表达，需要Cell Lab Quanta SC流细胞仪来分析细胞对磨损颗粒或用于假体周围骨溶解治疗的纳米球的反应（例如，使用多色激发分析颗粒吞噬、细胞活力、细胞凋亡、细胞增殖和不同的分子机制途径）。这项研究将导致使用纳米技术来调节假体周围骨溶解的新治疗方法的发展。结果也将显著增加我们目前对种植体失效机制的了解，并导致种植体寿命的延长。

Total joint arthroplasty, i.e., the complete artificial replacement of a natural joint (specifically hip and knee), is a surgical procedure that generally provides relief of pain and restoration of joint function. In 2003, more than 50,000 hip and knee replacements were performed in Canada, and 35% of these procedures were performed in patients less than 65 years old. Along with this increase in life expectancy has come a need to prolong prosthesis survivorship to avoid complex revision surgery and its associated morbidity and mortality. One of the major causes of total joint replacement failure is aseptic loosening due to bone destruction around the prosthesis (periprosthetic osteolysis). Wear particles have been demonstrated to be largely involved in the induction of periprosthetic osteolysis by stimulating the surrounding cells, leading to the release of inflammatory mediators. The goal of the proposed research is to identify the biological mechanisms involved in periprosthetic osteolysis by analyzing cell response to wear particles, and modulate this cell response and molecular mechanisms by using engineered nanospheres, specifically designed to target those cells and mechanisms. A laminar airflow workstation, a dual cell culture chamber and an ultra low-temperature freezer are requested to perform the cell culture and store cell and tissue samples at low temperature. A real-time PCR system is requested to analyze gene expression in macrophages exposed to wear particles, and a Cell Lab Quanta SC Flow Cytometer is requested to analyze cell response to wear particles or to nanospheres used for therapeutic treatments of periprosthetic osteolysis (e.g., analysis of particle phagocytosis, cell viability, cell apoptosis, cell proliferation and different molecular mechanisms pathways using multicolor excitation). This research will lead to the development of new therapeutic approaches using nanotechnology to modulate periprosthetic osteolysis. Results will also significantly add to our current knowledge on implant failure mechanisms and lead to the prolongation of implant longevity.