在骨科手術上，一旦發生植入後感染現象是非常棘手的併發症，不但可能造成植入的人工關節功能性不全需重新進行手術或慢性骨髓炎的發生，更可能造成敗血症而死亡。目前有許多研究企圖使用局部抗生素釋放系統來解決此問題，像局部抗生素骨水泥。但其釋放速度及濃度扔令人不滿意，另外在台灣，有些全髖關節置換手術並無使用骨水泥。因此發展一項金屬植入物它具有抗感染的效能是非常重要的。本實驗室先前體外測試結果顯示，利用雙層聚乳酸/甘醇酸(PLGA)包覆抗生素於鈦金屬盤上有效延長其抗生素釋放時間長達10天且無突釋現象產生。因此本研究目的將延續先前研究結果應用於體內測試，觀察利用PLGA包覆抗生素於鈦金屬絲是否有效預防骨髓炎發生。
在體外測試，我們利用抗生素釋放及抑菌圈進行評估經由雙層PLGA/cefuroxime 包覆於0.7 mm 噴砂處理過後的鈦金屬絲其抑菌效果。在體內測試方面，首先需建立具有骨髓炎之大鼠模型，利用X光片及組織染色來確認其誘發骨髓感染情況。隨後，分別將鈦金屬絲及雙層PLGA/cefuroxime包覆之鈦金屬絲植入於大鼠股骨髓腔內。利用Micro -CT 及組織病理切片檢測評估植入含有抗生素鈦金屬絲對於骨髓炎的治療效果。
在抑菌圈測試中，我們發現抗生素(cefuroxime)混合於PLGA溶液中扔具有其抑菌活性。而在抗生素釋放測試中，從鈦金屬絲上釋放出的抗生素濃度皆高於最低抑菌圈濃度(MIC)且釋放時間可達17天。
體內測試，藉由X光片證實注射108 CFU/0.5ml金黃色葡萄球菌液於大鼠股骨髓腔內確實可導致骨髓感染情況產生。且本研究所進行的植入鈦金屬絲手術流程是具有可行性且低死亡風險，另外更接近於臨床上進行髖關節置換手術部位。我們藉由Micro-CT分析實驗腳(左腳)與對照腳(右腳)的相對骨體積比及X光片予以比較，發現植入單純鈦金屬絲組其感染時間可達七周。然而，在PLGA/cefuroxime包覆組，其感染情況皆相對輕微。
總體而言，利用PLGA包覆抗生素於鈦金屬絲表面，並未破壞抗生素活性且確實有效延長其抗生素釋放時間長達17天在體外測試中。另外本研究成功建立具有骨髓炎之大鼠模型，且體內結果顯示雙層PLGA/cefuroxime 包覆組有效降低感染發生。

Implant-related infection is a catastrophic complication in orthopaedic surgery as it may result in poor functional outcome, chronic osteomyelitis, implant failure or even sepsis and death. Various local antibiotic delivery systems have been attempted, such as antibiotic-loaded bone cements, but the amount and rate of antibiotic release from bone cement is still not satisfactory. In Taiwan, some total hip arthroplasties were implanted without cement. It is important to develop metallic implants with anti-infective capacity. Our previous in vitro results using double layers of poly(lactic-co-glycolic acid) (PLGA) encapsulations on antibiotic coat-titanium discs had extended antibiotic releasing time without burst release up to 10 days. The purpose of this study continued our previous study to further test the efficacy of PLGA encapsulating antibiotic titanium pin in vivo in preventing osteomyelitis.
An in vitro elution test and direct contact inhibition zone for a 0.7 mm antibiotic sand blast titanium pin was conducted first to evaluate the anti-bacteria capacity of two PLGA/cefuroxime mixture encapsulation groups. For in vivo test, a rat osteomyelitis model was established and confirmed by x-ray morphology and histological staining, then a sand blasted titanium and a pin with double layer PLGA/cefuroxime mixture encapsulations were implanted into the femur cannel respectively. The more serious of the osteomyelitis is, the wider of the femoral shaft is. The proficiency of antibiotic loaded pin in treatment of osteomyelitis was examined by micro-CT and pathological investigations.
In vitro direct contact inhibition zone test showed cefuroxime could still be effective in disinfection after mixing with PLGA during encapsulation. The elution test showed the antibiotic release concentration from titanium pin higher than minimum inhibition concentration lasted near 17 days for double layer anti-biotic-PLGA mixture encapsulation group.
For in vivo results, the rat osteomyelitis model was established by directly injecting 108 CFU/0.5ml of Staphylococcus aureus into femur cannel and confirmed by x-ray images. Next, the implantation of pin into intramedullary cannel of rat was feasible with low mortality which was similar to the implantation of hip prosthesis in human. The osteomyelitis rat was persisted in infection up to 7 weeks in pure titanium pin implantation group, which was confirmed by femoral shaft width ratio between experimental and control leg and bone volume/tissue volume by micro-CT images and pathology analysis. However, in PLGA/cefuroxime encapsulation group, the infection was significantly relieved.
Overall, the antibiotic-PLGA mixture preparation for pin encapsulation did not destroy antibiotic activity, and could effectively extend the antibiotic release time in vitro up to 17 days. This study also successfully established the osteomyelitis rat model, and double layer PLGA/cefuroxime encapsulation group showed effective in long term infection prevention in vivo.

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