具有可調整降解特性之光交聯聚乳酸-聚乙二醇/ 聚己內酯-聚乙二醇複合水膠於軟骨細胞載體之研究

Controllable degradation properties of photocrosslinked PLA-b-PEG-b-PLA / PCL-b-PEG-b-PCL complex hydrogels for cell delivery

劉黃翔(Liou-Huang Siang)

指導教授 ： 朱一民

國立清華大學/工學院/化學工程學系/碩士(2013年)

https://doi.org/10.6843/NTHU.2013.00337

摘要

由於軟骨缺乏自我修復的能力，因此近年來軟骨治療已變成備受重視的問題，而組織工程技術可能是治療軟骨疾病的解決辦法。組織工程包含了細胞與支架，支架可以提供適合的環境讓組織再生及修復。水膠支架為三維立體網狀結構，其具有高含水率、高質傳效率及可均勻包埋細胞等優點，因此近年來被廣泛使用在組織工程。
本研究擬設計由聚乳酸-聚乙二醇及聚己內酯-聚乙二醇所組成光交聯複合水膠，其具有生物降解性及生物相容性。此光交聯水膠可做為包埋軟骨細胞的軟骨生成支架，研究中將調控不同的聚乳酸-聚乙二醇及聚己內酯-聚乙二醇之混摻比例，以達到適當之降解性質。藉由1H-NMR、FT-IR及GPC確認材料的化學結構，並經由DSC和膠含量確認水膠的基本性質。PBS降解測試中，L50C50及L25C75可維持較適當的降解速率以及減緩環境酸化的問題。由SEM的結果顯示，水膠的孔洞大小隨著降解時間增加而變大。當水膠包埋軟骨後培養於軟骨化培養基內進行觀察，L50C50及L25C75水膠依然表現較理想的降解速率。基因表現則可觀察到各混摻水膠在2週培養的過程中，軟骨蛋白聚糖以及二型膠原蛋白的基因表現會逐漸上升，而一型膠原蛋白的基因表現則會隨著時間增加而逐漸下降，符合關節軟骨之正常分化狀態。由生物化學的組成和組織學結果得知L50C50比起其他混摻水膠而言，有較佳的細胞外間質累積的情形。此研究結果將有助於軟骨組織工程之用的水膠材料開發，未來期望可做為關節軟骨組織工程之應用。

關鍵字

光交聯水膠 ； 降解特性 ； 軟骨細胞

並列摘要

Due to the cartilage’s poor self-repairing capacity, cartilage repairs have become a growing concern. Tissue engineering has been proposed as an alternative method to repair diseased cartilage. Tissue engineering consists of cells and a biodegradable scaffold, the latter provides a suitable environment for tissue repairs and regeneration. Hydrogel scaffolds are three-dimensional in structure and are promising substrates for tissue engineering applications due to their high water content, efficient mass transfer, and ability to homogenously encapsulate cells.
In this work, we fabricated complex biodegradable and biocompatible hydrogels based on PLA-b-PEG-b-PLA (PEL) and PCL-b-PEG-b-PCL (PEC) via photo-crosslinking. These hydrogels can be used as scaffolds for chondrocyte encapsulation in cartilage tissue engineering. This study investigated the effect of the blend ratio of PEL and PEC on the hydrogel properties. The chemical structure of the copolymers can be confirmed by 1H-NMR, FT-IR and GPC. The hydrogel properties were measured by the DSC and gel content. On the degradation behavior in PBS buffer solution, L50C50 and L25C75 had a suitable degradation rate. Excess acidity could be solved through controlled the blend ratio. The same results were showed in chondrogenic medium. The SEM images showed that the pore sizes of the hydrogels were increased as the degradation time. Gene expression of encapsulated chondrocytes with different blend ratio of PEL and PEC demonstrated that aggrecan and collagen II were increased within first 2 weeks. The collagen I were decreased with culture time. Compared to other blend ratio, L50C50 hydrogels revealed a higher level accumulation of cartilage extracellular matrix by biochemical and histological analysis. Results of this study will benefit the development of hydrogel scaffolds in cartilage tissue-engineering.

並列關鍵字

Photo-crosslinked Hydrogel ； Degradation property ； Chondrocyte

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