添加基質細胞衍生因子－1之明膠/透明質酸水膠混合硫酸鈣及氫氧基磷灰石用於骨再生之研究

對於臨床骨科醫師而言，病人的骨缺損往往是在手術治療時的一項巨大挑戰。除了最常見的外傷性骨缺損之外，腫瘤或感染的侵蝕也是造成骨缺損的常見原因。為了要讓病人達到良好的骨癒合，臨床骨科醫師在處理這類有骨缺損的病例時，除了必要的骨折復位及內固定手術之外，通常還會需要在骨缺損處填入一些移植骨或補骨填充物以利癒合，否則若骨缺損的範圍較大，便很有可能出現延遲癒合或是不癒合的狀況，造成後續治療的困難。除了自體骨或異體骨移植之外，臨床上早期所常用的補骨填充物多為硫酸鈣或磷酸鈣這類可以提供骨傳導和一定程度力學支撐的人工合成骨替代物。但隨著像鎖定式鋼板等內固定系統的演進，臨床治療上對於骨填充物所帶來的骨誘導性要求已經漸漸超越了力學上的需求，例如目前常用的去礦化骨基質以及一些含有生長因子的骨填充物等等。除了骨塑型蛋白及一些較為人所知的生長因子之外，近年來研究發現基質細胞衍生因子－1具有吸引間質幹細胞的能力，進一步還可促進和調節骨骼之發育和生成，顯示其具有相當的骨誘導性。本研究即使用基質細胞衍生因子－1搭配具有良好生物相容性及可吸收性的透明質酸水膠、明膠、硫酸鈣及氫氧基磷灰石等製成複合材料，經由X光繞射分析儀及傅立葉紅外線光譜儀驗證複合材料的組成及交聯的成功，再透過生物相容性測試及間質幹細胞吸引測試確認複合材料的生物相容性及其吸引間質幹細胞的能力，最後藉由在大鼠股骨上製造骨缺損模型的動物實驗以及後續包含的血液分析、微型電腦斷層造影、二倍頻顯微造影以及組織染色等，分析並證明複合材料之安全性及其促進骨再生之能力。經實驗證明，本研究製備之含有基質細胞衍生因子－1之複合材料同時具有良好的骨誘導性及生物相容性，再搭配上優秀的可操作性及其促進骨癒合的能力，期望將來能確實應用於骨缺損之臨床治療。

關鍵字

骨缺損；骨誘導性；基質細胞衍生因子－1 ；透明質酸；明膠；硫酸鈣；氫氧基磷灰石

並列摘要

In clinical practice, bone defects still remain a challenge. In recent years, apart from the osteoconductivity that most bone void fillers already provide, osteoinductivity has also been emphasized to promote bone healing. Stromal-cell-derived factor-1 (SDF-1) has been shown to have　the ability to recruit mesenchymal stem cells (MSCs), which play an important role in the bone regeneration process. In this study, we developed a gelatin–hyaluronate (Gel-HA) copolymer mixed, hydroxyapatite (HAP), and SDF-1 with or without calcium sulfate (CS) in order to enhance bone regeneration in a bone defect model. These composites were tested in vitro for biocompatibility and their ability to recruit MSCs after material characterization. For the in vivo test, a rat femoral condyle bone defect model was used. Micro computed tomography (micro-CT), second harmonic generation (SHG) imaging, and histological analysis were performed to assess bone regeneration. As expected, enhanced bone regeneration was well observed in the group filled with Gel-HA/CS/HAP/SDF-1 composites and Gel-HA/HAP/SDF-1 composites compared with the control group in our animal model. Furthermore, detailed blood analysis of rats showed no obvious systemic toxicity or side effects after material implantation. In conclusion, the Gel-HA/CS/HAP/SDF-1 and Gel-HA/HAP/SDF-1 composites may be a safe and applicable alternative to enhance bone regeneration in bone defects.

並列關鍵字

bone defect, ； osteoinduction ； stromal cell-derived factor-1 ； hyaluronic acid ； gelatin ； calcium sulfate ； hydroxyapatite

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