水膠具有高含水率的特性，因此常被利用在軟骨組織工程的應用，但因大多數的水膠不具有良好的機械性質往往限制了它的表現及應用。本研究的目的是合成一種具有良好生物相容性、高機械強度、高含水率及具有孔洞結構的水膠，並將其應用在軟骨的再生醫學。本研究中，選用瓊脂糖作為第一種具網狀結構的材料，因為其高含水率的特性、具有與軟骨組織相似的微結構，且能幫助軟骨細胞的生長等特性，已被廣泛地應在軟骨組織工程。另外，經由開環聚合的方式合成三嵌段共聚物(PEC)，作為第二種同樣具有三維網狀結構的材料。PEC是一種可照光交聯的高分子，具有良好機械性質、可調控分子量的特性，且可提供軟骨細胞與幹細胞極佳的生長環境。互穿網狀結構(IPN)的合成方法是將PEC利用浸泡擴散至瓊脂糖內部，經照光交聯後形成水膠。本研究利用成骨細胞的細胞存活率與細胞型態呈現生物材料的細胞毒性與生物體外之相容性。動物實驗中，將不含細胞的生物材料分別植入大鼠背部與膝蓋骨軟骨缺損的區域，觀察其生物體內之相容性，檢測軟骨再生的程度是利用切片染色的方式觀察大鼠膝關節植入物中細胞的分布、型態與膠原蛋白等組成，進而比較分別植入IPN與PEC水膠對於軟骨修復的效果。本研究有以下幾點結論：互穿網狀結構有助於提升材料之機械性質；高含水率及更均勻的多孔結構可以在互穿網狀結構中被發現；IPN在生物體外與體內的降解速率比PEC慢；圓球狀的軟骨細胞被發現在新生軟骨組織的骨穴結構中，具有大量細胞質與膠原蛋白圍繞，是典型的軟骨組織的結構；PEC組別中發現軟骨往下生長影響軟骨下區正常分布之現象；IPN組別表現較佳的水膠的完整性，有效地防止軟骨往下生長，適合做為長期軟骨組織修復的填充材料。因此，此具有可調控特性的互穿網狀結構材料，有助於細胞外間質的分泌，是適合應用在軟骨組織工程的生物材料。

Hydrogels are suitable biomaterials for cartilage tissue engineering due to the excellent ability to retain water for nutrient and waste transport, however, the insufficient mechanical properties restrict the further applications. The objective of this study was to fabricate biocompatible hydrogels with good mechanical performance, high water content, and porous microstructure for cartilage regeneration. In this study, block copolymer, poly(ɛ-caprolactone)-poly(ethylene)-poly(ɛ-caprolactone) diacrylate (PCL-PEG-PCL; PEC), was prepared by ring-opening polymerization, and PEC hydrogels can be formed through free radical crosslinking mechanism. Agarose network is chosen as another component because of the high swelling behavior and cartilage-like microstructure, which is helpful for chondrocytes growth. Interpenetrating networks (IPN) were fabricated by diffusing PEC into agarose network followed by photo-crosslinking process. It was noted that incorporating PEC into the agarose network increased the elastic modulus and the compressive failure properties of individual component networks. In addition, high swelling ratio and uniform porosity microstructures were found in the IPN hydrogels. According to the results of osteochondral repair for IPN and PEC, round chondrocytes were contained within lacunae in the regenerated tissue in which much cytoplasm and collagen were found. However, obvious down growth of cartilage were found in PEC group; by contrast, the IPN showed the feature of maintaining the integrity of hydrogels, preventing cartilage form disrupting subchondral bone. Consequently, IPN hydrogel with adjustable properties could be a potential biomaterial supporting cell growth as well as ECM secretion for cartilage tissue engineering.

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