人工關節摩擦後產生的超高分子量聚乙烯(UHMWPE)磨耗顆粒,會在人體內刺激巨噬細胞(macrophage)分泌細胞激素(cytokine),促進蝕骨細胞(osteoclast)的分化,進而引發骨溶解(osteolysis)現象,造成人工關節發生鬆脫 (aseptic loosening),必須實施人工關節再置換。因此為了解決人工關節置換術後的骨溶解之問題,我們製備次微米UHMWPE 磨耗顆粒並建立骨溶解現象之動物模型,以提供將來作為治療與預防的平台。 故本研究利用半導體中的微影製程(microfabrication),在4吋晶圓上製作微米加工表面(surface texture),而加工表面上設計有微米尺寸的切割裝置(cutting device),藉由此裝置我們可以將UHMWPE 棒材與加工表面進行加速磨耗試驗,製備次微米尺寸之磨耗顆粒。在動物實驗方面,為了模擬臨床上置換人工關節之情形,將大鼠股骨位置植入不銹鋼管,並且注射次微米磨耗顆粒懸浮液於膝關節腔內,探討磨耗顆粒對於大鼠關節腔周圍發生骨溶解之嚴重性。 結果發現組織切片上,可觀察到植入物周圍有纖維化組織(fibrous tissue)增生、大量多核巨細胞(multinucleated giant cell)聚集包覆UHMWPE 磨耗顆粒,以及異常的蝕骨細胞(osteoclast)表現,但是植入物與切片位置皆會影響發炎反應之表現。因此,往後實驗設計上,需尋求解決實驗ㄧ致性之問題,以建立有效且可靠的動物模型,作為骨溶解研究之基礎。
Osteolysis induced by UHMWPE wear debris has been recognized as the major cause of long-term failure in total joint arthroplasty. It is thought to be due to a cascade of events, including production of wear particles from the bearing surfaces and other implant interfaces, secretion of cytokines by macrophages, stimulation of osteoclast differentiation, induction of osteolysis and aseptic loosening. Thus, it is crucial to establish an animal model for analyzing the influence of UHMWPE particles on inducing osteolysis. However, it is difficult to obtain sufficient amount of UHMWPE particles from human tissues. Therefore, this study aimed to establish a process for generating large amount and consistent size of UHMEPE particles. A preliminary animal study was further established to analyze the possible mechanism causing particle-induced osteolysis. In this study, we applied microfabricated surface texture to rub against the UHMWPE pins in order to generate sub-micrometer wear particles. In vivo animal model, we implant steel tube in the proximal tibia, then intra-articular injections of sub-micrometer wear particles per joint were given for couple weeks after surgery. Results from the animal study demonstrated that UHMWPE particles play an important role on inducing inflammatory osteolysis. Specific mechanism causing osteolysis should be further justified. The established technique platforms of particle- generating process and the animal study procedure can be used for further applications.