溫感性水膠複合材料於植入式骨組織再生應用之研究

本研究主要探討以可降解性之溫感性水膠，如聚乙二醇-聚乳酸/甘醇酸之雙團聯共聚物，應用於軟硬骨組織再生中之可能性評估。實驗以開環聚合法，製備多種聚乙二醇-聚酯雙團聯共聚物，經由生物相容性評估後，篩選出聚乙二醇-聚乳酸/甘醇酸（mPEG-PLGA），聚乙二醇-聚乳酸/戊內酯（mPEG-PVLA），聚乙二醇-聚乳酸/己內酯（mPEG-PCLA）等三種材料，進行後續之兔子軟硬骨缺損模式試驗。硬骨缺損模式中：先經由四週之評估期後，結果顯示mPEG-PLGA組之硬骨再生能力優於mPEG-PVLA組。因此，後續實驗更進一步的將mPEG-PLGA複合對骨母細胞生長有活性之生醫材料，如：氫氧基磷灰石（Hydroxyapatite, HAp），三鈣磷酸鹽（β-tricalcium phosphate, TCP）。評估複合植入材之物理/化學性質與生物相容性後，植入兔子大腿骨非癒合型之骨缺損之中。植入三個月之後，犧牲動物體，並以電腦斷層掃瞄(μCT)，骨質密度儀(BMD)，組織切片染色分析。初步結果顯示，mPEG-PLGA複合HAp/TCP(7:3)者，其骨組織再生最優。軟骨缺損模式中：選用mPEG-PCLA複合膠原蛋白二型或TGFβ-3生長因子之複合植入材，植入兔子膝蓋軟骨缺損之中。八週之評估期後，犧牲動物體，並以組織切片染色分析。初步結果顯示，其對軟骨修復有明顯效果。綜由上述之研究成果顯示：溫度敏感型聚乙二醇-聚酯類之雙團聯共聚物，可簡易複合式多種具骨誘導因子，如HAp，TCP與TGF-β3，並且對軟硬骨缺損有修復之成效，適合於臨床醫療上開發。

關鍵字

溫感水膠；硬骨；軟骨；複合材料；再生

並列摘要

The objective of this research was to discuss the biodegradable thermo-sensitive hydrogel, such as methoxy poly(ethylene glycol)-poly(lactic-co-glycolic acid), mPEG550-PLGA1405, applies to bone tissue regeneration. Several diblock copolymers were synthesized undergoing ring-opening polymerization process. After biocompatibility test, we chose mPEG-PLGA, mPEG-PVLA ( methoxy poly(ethylene glycol)-poly(lactic acid-co-valerolactone) and mPEG-PCLA ( methoxy poly(ethylene glycol)-poly(lactic acid-co- caprolactone) to utilize in rabbit bone defect model. Four weeks later, the result of bone defect regeneration revealed the mPEG-PLGA implant experiments were superiorly than mPEG-PVLA implant experiments. Moreover, mPEG-PLGA were blending with hydroxyapatite (HAp), β-tricalcium phosphate (TCP) to form into a implant composite for rabbit non-union critical-size model. X-ray evaluated bone formation every four weeks postoperatively. The rabbits were sacrificed 12 weeks postoperatively then their femur bones were harvested for micro-computed tomography(μCT), bone mineral density (BMD) and histology study. The results validated the usage mPEG-PLGA/HAp/TCP(7:3) as bone graft substitute. We chose mPEG-PCLA with collagen type II or TGFβ-3 for rabbit cartilage defect model. After eight weeks implant, the rabbits were sacrificed and evaluated by histology. The results validated mPEG-PCLA/collagen type II/ TGF-β3 composites can enhance cartilage repair. Summarily, the biodegradable thermo-sensitive mPEG-poly ester copolymer composites were suitable for bone/cartilage tissue regeneration.

並列關鍵字

thermogel ； bone ； cartilage ； composite ； regeneration

參考文獻

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溫感性水膠複合材料於植入式骨組織再生應用之研究

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