生物可降解水性製程之聚胺酯組織工程支架之評估

近期高分子產業趨勢之一為發展環保綠色製程或是可降解產品，而綠色製程之生物可降解高分子作為生醫材料或組織工程支架其需求更甚。本研究以水性製程合成生物可降解聚胺酯(polyurethane, PU)，並形成奈米分散液，成分中的軟鏈段使用兩種聚酯二元醇，分別為poly(ɛ-caprolactone) diol和poly(ethylene-co-butylene adipate) diol，再以冷凍乾燥製備成三維海綿狀多孔支架。PU支架製備後進行其結構鑑定、潤濕性、機械性質、降解行為與降解產物分析，並探討支架孔洞結構對機械性質之影響與不同體外降解環境之降解機制分析。將軟骨細胞植入支架，並置於靜態或動態條件下培養，進行軟骨細胞外基質分泌與人類骨髓幹細胞(MSCs)基因表現分析。得本研究合成之PU奈米粒粒徑為約於40 nm，獲得的PU支架不僅具有良孔洞連通性，且其孔洞結構為螺旋形態。支架之親水性佳，且具有高的孔隙率和吸水率。在機械性質方面，除PU之固有彈性外，其螺旋型孔洞結構亦是支架拉伸與壓縮性質佳之主因。PU支架之動態機械性質無論是於乾燥或是濕潤之狀態下，其儲存模數值皆隨頻率增加而上升，顯現其彈性特質。PU支架在37℃磷酸鹽緩衝液中之降解速率較在木瓜蛋白酶消化液和去離子水顯著。由支架降解產物分析推測降解過程先進行膨潤，再進一步酯基水解，且細胞毒性不顯著。而PU支架之收縮情形可由二次冷乾的方法改善。在體外軟骨細胞生長測試中，軟骨細胞於靜態中PU支架較PLA支架內分布均勻，PLA細胞大部分分布於表層中；細胞在動態環境下培養7日之生長較靜態佳。於動態環境培養下，細胞外基質會部分流失至培養液中，而PU支架較PLA支架內細胞外基質分泌量稍高，且細胞於PU支架分布均勻，可能為其GAG保留於細胞中含量較高之原因之一。而支架MSCs以軟骨分化液培養七日，PU支架軟骨基因表現較PLA支架佳。綜合以上之優勢，PU支架有應用於軟骨組織工程發展之潛力。

關鍵字

水性生物可降解聚胺酯；支架；降解；彈性；軟骨

並列摘要

Biodegradable polyurethane (PU) was synthesized by a green and sustainable water-based process. The process rendered homogenous PU nanoparticles (NPs). Spongy PU scaffolds in large dimension were obtained by freeze-drying the PU NP dispersion. The spongy scaffolds were examined in terms of the porous structure, wettability, mechanical properties, degradation behavior, and degradation products. The capacity as cartilage tissue engineering scaffolds was evaluated by growing chondrocytes and mesenchymal stem cells (MSCs) in the scaffolds. Scaffolds made from PU dispersion had excellent hydrophilicity. The scaffolds had high porosity and water absorption. Examination by micro-computed tomography confirmed that PU scaffolds had good pore interconnectivity. The degradation rate of the scaffolds immersed in phosphate buffered saline was much faster than that in papain solution or in deionized water at 37 oC. The biodegradable PU appeared to be degraded via the cleavage of ester linkage, judging from the degradation products. The intrinsic elastic property of PU and the gyroid-shape porous structure of the scaffolds may have accounted for the outstanding strain recovery (87 %) and elongation behavior (257 %) of the PU scaffolds, compared to conventional poly(D,L-lactide) (PLA) scaffolds. Chondrocytes were effectively seeded in PU scaffolds without pre-wetting. They grew better and secreted more glycosaminoglycan in PU scaffolds vs. PLA scaffolds. Human MSCs showed greater chondrogenic gene expression in PU scaffolds than in PLA scaffolds after induction. Based on the favorable hydrophilicity, elasticity, and regeneration capacities, the novel biodegradable PU scaffolds may be superior to the conventional biodegradable scaffolds in cartilage tissue engineering applications.

並列關鍵字

Biodegradable polyurethane ； scaffold ； elasticity ； degradation ； cartilage

參考文獻

[1] Goering H, Krüger H, Bauer M. Multimodal polymer networks: design and characterisation of nanoheterogeneous PU elastomers. Macromol Mater Eng 2000;278:23–35.

[2] Santerre JP, Woodhouse K, Laroche G, Labow RS. Understanding the biodegradation of polyurethanes: from classical implants to tissue engineering materials. Biomaterials 2005;26: 7457–7470.

[3] Wiggins MJ, MacEwan M, Anderson J M, Hiltner A. Effect of soft‐segment chemistry on polyurethane biostability during in vitro fatigue loading. J Biomed Mater Res A 2004;68: 668–683.

[4] Guelcher SA. Biodegradable polyurethanes: synthesis and applications in regenerative medicine. Tissue Eng: Part B 2008;14:3–17.

[5] Rao JP, Geckeler KE. Polymer nanoparticles: Preparation techniques and size-control parameters. Prog Polym Sci 2011;36:887–913.

國際替代計量

生物可降解水性製程之聚胺酯組織工程支架之評估

全文下載

主題瀏覽