| 摘要: | 傷口癒合是一個包含止血、發炎、增生與重塑等階段的複雜生理過程，其中長期的慢性發炎反應常導致傷口修復延緩，尤其在糖尿病或老年患者中更為明顯。為同時改善慢性發炎與促進組織再生，本研究以褐藻酸鈉與殼聚醣開發多功能複合敷料：褐藻酸鈉提供高親水性、維持傷口濕潤，並釋放鈣離子促進止血；殼聚醣則具抗菌性，可促進細胞貼附生長並預防感染。我們在殼聚醣纖維中加入抗發炎藥物白楊素(Chrysin)，並透過聚乳酸(PLA)控制其緩釋。體外實驗顯示，白楊素可抑制RAW264.7巨噬細胞iNOS表達與IL-6分泌，並具抗氧化作用，有效減少發炎。利用共混電紡技術製備不同比例的褐藻酸鈉與殼聚醣/聚乳酸複合纖維，所製得的複合纖維具備均勻且連續的結構，機械性質與人類皮膚相近。親疏水性可依材料比例調控，加入殼聚醣/聚乳酸提高纖維疏水性，促進細胞貼附。進一步以聚乙烯亞胺(PEI)吸附PDGFB基因形成正電奈米顆粒並固定於褐藻酸鈉纖維上，可原位轉染貼附細胞，促進細胞增生。動物實驗結果顯示，複合纖維敷料能持續釋放PDGFB促進膠原蛋白生成，加速傷口修復；白楊素則抑制發炎細胞浸潤，降低發炎對組織的影響。綜合而言，本研究建立一種可同時釋放生長因子基因與抗發炎藥物的多功能複合纖維敷料，可提供傷口保護、抗發炎並促進組織再生，展現應用於慢性傷口之高度潛力。;Wound healing is a complex biological process involving hemostasis, inflammation, proliferation, and remodeling, in which prolonged inflammation often leads to delayed repair, particularly in diabetic or elderly patients. To simultaneously modulate inflammation and promote tissue regeneration, this study developed a multifunctional composite dressing composed of sodium alginate and chitosan. Sodium alginate (Alg) exhibits high hydrophilicity, which helps maintain a moist wound environment. Furthermore, calcium ions can be released from crosslinked Alg to facilitate hemostasis. Chitosan (CHI) offers antibacterial properties, improves cell adhesion, and prevents infection. Chrysin, an anti-inflammatory drug, was loaded into chitosan fibers, and its sustained release was controlled by the incorporated polylactic acid (PLA). In vitro experiemnts showed that chrysin from CHI/PLA fibers reduced iNOS expression and IL-6 secretion in RAW264.7 cells, suggesting its antioxidant and anti-inflammatory effects. Composite fibers of Alg and CHI/PLA were prepared by co-electrospinning, which exhibited uniform morphology, tunable hydrophilicity, and mechanical properties comparable to human skin. The incorporation of CHI/PLA fibers increased hydrophobicity and enhanced cell attachment. The positively charged nanoparticles formed by polyethylenimine (PEI) and PDGFB gene complexation can be adsorbed to Alg fibers to in situ transfect cells for proliferation promotion. In vivo wound healing experiments on mice confirmed that PDGFB-loaded dressing markedly enhanced wound closure, collagen formation, and and epithelial regeneration. Furthermore, chrysin released from dressing reduced inflammatory infiltration. Overall, this study establishes a dual-functional Alg/CHI-PLA electrospun dressing capable of synergistic anti-inflammatory and pro-regenerative effects, demonstrating great potential for application in the treatment of chronic wounds. |
