急性肺損傷是一種具有高發病率和死亡率的嚴重臨床症候群及肺部疾病，其病理機轉主要是當肺部受損時會產生急性的發炎反應，肺泡嗜中性細胞及巨噬細胞，會釋放細胞激素召集嗜中性白血球，導致病理上出現肺泡受損、嗜中性白血球浸潤、肺間質水腫等之情形。而細胞外基質為組織萃取物是天然的生物材料，成分為多種蛋白質及醣類的結構，生物相容性高，常被作為細胞生長支架，應用在器官修復與疾病治療，是具有潛力的生物材料；因此藉由脫細胞方法製備細胞外基質以調節巨噬細胞發炎反應。
本研究利用物理和化學的脫細胞方法，去除豬肺臟的細胞並萃取細胞外基質，進行殘存細胞和藥劑分析，避免產生排斥反應，藉由細胞外基質生化特性分析和細胞抗發炎分析，最後製備出適合用於肺部傳輸之細胞外基質微奈米顆粒，進行動物發炎分析，評估細胞外基質對於治療和預防急性肺損傷之效果。
研究結果顯示，本實驗所使用之脫細胞方法，使每1mg的豬肺臟dsDNA含量低於50ng，成功將豬肺臟細胞去除，並保留了膠原蛋白含量，可成功製備成水凝膠；細胞2D及3D培養結果顯示，細胞外基質提供良好的細胞生長環境，無生物毒性且生物相容性高；細胞抗發炎實驗結果顯示，細胞外基質具有抗發炎效果；所製備之細胞外基質微奈米顆粒之粒徑大小介於222.48-878.08nm，平均粒徑為 447.39 ± 213.77nm，適合於肺部傳輸且利於巨噬細胞吞噬；動物抗發炎實驗結果顯示，細胞外基質具有抗發炎效果，有抑制及預防肺組織產生嗜中性白血球浸潤與聚集之免疫調節效果。

Acute lung injury (ALI) is a severe clinical syndrome and lung disease with high morbidity and mortality. The pathological mechanism is mainly that when the lungs are damaged, an acute inflammatory reaction will occur, and alveolar neutrophils and macrophages will release cytokines to recruit neutrophils, resulting in pathological alveolar damage and neutrophils. It appears that conditions such as neutrophil infiltration, pulmonary interstitial edema, etc. The extracellular matrix (ECM) is a native tissue extract, a structural support network comprising diverse proteins, sugars, and other components. It has high biocompatibility and is often used as a cell growth scaffold for organ repair and disease treatment. It is a potential biological material; Therefore, using the decellularized ECM regulates the inflammatory response to macrophages.
This study uses physical and chemical decellularization methods to remove cells from porcine lungs and extract the extracellular matrix. We analyzed the residual cells and drugs to avoid rejection. The extracellular matrix's biochemical characteristics and the anti-inflammation effects were also studied. The extracellular matrix hydrogel micro-nanoparticles were prepared to the size suitable for pulmonary delivery. The anti-inflammatory effects of ECM hydrogel micro-nanoparticles were evaluated to treat and prevent ALI in a rat model.
The results showed that our decellularization method successfully removes the cells from the lung tissue; the content of residual dsDNA per 1 mg of porcine lungs was less than 50ng. The resulting decellularized ECM (dECM) retains most of the ECM components, such as collagen and GAGs, and can be used to prepare ECM hydrogel. The dECM hydrogels exhibit no biotoxicity and high biocompatibility. The cell growths in ECM hydrogels were higher than the collagen control group in both 2D and 3D cell culture environments and exhibited higher anti-inflammatory ability in vitro. The results showed that the dECM hydrogel particle sizes of micro-nanoparticles ranged from 222.48 to 878.08nm. The average particle size is 447.39 ± 213.77nm, suitable for pulmonary delivery and conducive to macrophage phagocytosis. More importantly, the in vivo experiment showed that dECM hydrogel particles have great potential in treating and preventing ALI. It has the immunoregulatory effect of inhibiting and preventing neutrophil infiltration and aggregation in lung tissue.

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