背景與目的: 關節軟骨在受傷後自我修復能力差。目前，在臨床上已有許多治療方法，然而，仍存有併發症，例如：生成纖維軟骨、不穩定性、植入物失敗等。組織工程，包含細胞、細胞支架、環境讓細胞生長，提供一個較新的方法去修復損傷的軟骨。迄今，生醫細胞、支架材料、培養環境仍沒有最好的配對，這仍然是當今組織工程與再生醫學熱門的研究領域。本研究目的是製備聚乳酸/甘醇酸海綿支架與聚乳酸/甘醇酸-明膠與透明質酸複合式支架提供未來軟骨軟骨組織工程之應用。

材料與方法: 製備聚乳酸/甘醇酸海綿支架使用鹽析法。聚乳酸/甘醇酸-明膠與透明質酸支架經由EDAC交聯劑修飾支架表面。聚乳酸/甘醇酸支架與聚乳酸/甘醇酸-明膠與透明質酸支架分別評估其結構、成份元素分析、吸水量、力學測量以及體外降解測試。從豬關節萃取得初代軟骨細胞用來評估在細胞支架之生物相容性。我們評估細胞貼附率、細胞形態、細胞外基質合成量以及細胞增生。

結果與討論: 由鹽析法製備的聚乳酸/甘醇酸支架，其孔洞大小被控制在我們想要的300~500μm與90%以上孔洞率。聚乳酸/甘醇酸-明膠與透明質酸支架在電子顯微鏡觀測下有較平滑的表面。藉由成份元素分析顯示氮元素存在於細胞支架上，證明交聯劑能有效交聯明膠與透明質酸在聚乳酸/甘醇酸支架上。因為親水性關係，吸水量在早期聚乳酸/甘醇酸-明膠與透明質酸支架顯著性地的兩倍高於聚乳酸/甘醇酸支架。聚乳酸/甘醇酸支架與聚乳酸/甘醇酸-明膠與透明質酸支架之壓縮楊氏係數的平均值分別為3.75±0.74MPa和1.27±0.18MPa。在體外降解測試，聚乳酸/甘醇酸支架之重量減少明顯的少於親水性的聚乳酸/甘醇酸-明膠與透明質酸支架。降解後，聚乳酸/甘醇酸支架之結構仍然可以維持外型，但是聚乳酸/甘醇酸-明膠與透明質酸支架因為塊狀腐蝕有不規則外形。
細胞貼附率在聚乳酸/甘醇酸-明膠與透明質酸支架也顯著性地高於單純聚乳酸/甘醇酸支架。在整個培養過程中，兩組支架均能使軟骨細胞維持形態，而且在聚乳酸/甘醇酸-明膠與透明質酸支架上細胞明顯地有較大之攤附面積與群聚現象。在細胞增生期時，葡萄糖胺聚合醣及醣蛋白顯示在兩組間有可見性的差異。此外，細胞增生測試顯示聚乳酸/甘醇酸-明膠與透明質酸支架比只有聚乳酸/甘醇酸支架還要好。

結論: 本研究顯示聚乳酸/甘醇酸支架經由明膠與透明質酸修飾後呈現出較好的生物可相容性、適當的力學特性、細胞外基質合成量、細胞增生，以應用於潛能性之工程軟骨。

Background and purpose: Articular cartiage has a poor self-repaired capability after injury. So far, several treatment methods have been applied in clinic. Howerver, some complications still existed, such as fibrocartilage scar tissue formation, instability, implantion failure and so on. Tissue engineering, combining cells, scaffolds, and envirnment to grow tissue, provides a new strategy to repair damaged cartilage. To date, the best cell source, scaffold material and articature and culture condition used for tissue engineering are still hot topic in research field. The aim of this work is to fabricate and characterize the PLGA and PLGA-gelatin/Hyaluronic acid (PLGA-GH) sponge scaffolds for future cartilage tissue engineering applications.

Materials and methods: The PLGA sponge scaffold was fabricated by salt leaching method. The PLGA-GH scaffold was modified with gelatin and hyaluronic acid by 1-ethyl-3-(3-dimethyl-aminopropyl) carbodiimide (EDAC) cross link agent. Structure, Element analysis, water uptake ratio, mechanical test, and in vitro degradation tests were evaluated for both PLGA and PLGA-GH scaffolds. Primary chondrocytes, isolated from porcine articular cartilages, were used to evaluate the cell compatibility of scaffolds. We evaluated cell attachment ratio, cell morphology, extracellular matrix synthesis, and cell profileration.

Results and discussion: The pore size of PLGA scaffold fabricated by salt leaching was controlled within 300 to 500 μm with over 90% porosity as we desired. PLGA-GH scaffold has exhibited smother surface observed by SEM. The appearance of nitrogen on PLGA-GH scaffold examined by EDS proved EDAC could link gelatin and HA on PLGA scaffold. PLGA-GH was twice higher in water uptake ratio than PLGA scaffolds in early stage due to its hydrophilic surface. The mean comprssive moduli of PLGA and PLGA-GH scaffolds were 3.75±0.74MPa and 1.27±0.18MPa, respectively. In vitro degradation test, weight loss of PLGA scaffold was significantly less than hydrophilic PLGA-GH. Post degradation, the structure of PLGA scaffolds can be maintained, but PLGA-GH scaffolds had an irregular morphology due to bulk erosion. Cell attachment ratio on PLGA-GH scaffold was also significantly higher than PLGA alone. Both PLGA and PLGA-GH scaffolds can retain chondrocye phenotypes during culture, and cells attached on PLGA-GH scaffold had obviously larger spreading areas, and cluster. The GAGs and PGs synthesis were remarkable different between PLGA and PLGA-GH scaffolds during proliferation. Moreover, PLGA-GH scaffold had better proliferation than PLGA scaffold.

Conclusion: Our study had showed that PLGA scaffold after modified with gelatin and hyaluronic acid displayed better cell biocompatibility, appropriate mechanical properties, extracellular matrix synthesis, and cell proliferation for potential engineering cartilage.

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