Decellularization compromises mechanical and structural properties of the native trachea.
Decellularization compromises mechanical and structural properties of the native trachea.
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DOI：
10.1016/j.bbiosy.2023.100074
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发表时间：
2023-03
影响因子：
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通讯作者：
Niklason, Laura E
中科院分区：
文献类型：
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作者：
Greaney, Allison M;Ramachandra, Abhay B;Yuan, Yifan;Korneva, Arina;Humphrey, Jay D;Niklason, Laura E
任何去细胞化都会损害气管软骨、气管和结缔组织。治疗导致Coll-II和GAG的损失，导致软骨环塌陷。任何治疗都会丢失Col-III，而Col-I则会变得杂乱无章并降解。气管肌肉变得更加顺应收缩SMC的损失。轴向力学由胶原结构和纵向弹性蛋白纤维控制。使用组织工程技术的气管置换提供了巨大的潜力，以改善以前棘手的临床干预，并在这方面的兴趣近年来有所增加。目前，许多工程气道结构依赖于脱细胞的天然气管作为组织修复的支架。然而，导致气道狭窄和塌陷的机械故障仍然是脱细胞气管移植物临床植入后发病率和死亡率的主要原因。为了更好地了解体内机械故障的因素，我们在两种不同的脱细胞方案，包括一个已用于临床的组织力学特性的气管。所有脱细胞气管偏离天然力学行为，这可能会提供观察到的体内移植失败的见解。我们进一步通过蛋白质印迹分析蛋白质含量，并通过组织学染色分析显微结构，发现特定的脱细胞方法导致蛋白多糖的消耗和胶原蛋白I，II，III和弹性蛋白的降解存在显着差异。总之，这项工作表明，气管的异质结构和机械行为是严重受损的脱细胞化。这种结构退化可能导致移植失败的临床和限制的潜力脱细胞天然气管作为可行的长期原位气道替代。
Any decellularization impairs tracheal cartilage, trachealis, and connective tissue. Treatment causes loss of Coll-II and GAGs, leading to collapse of cartilage rings. Coll-III is lost with any treatment whereas Col-I becomes disorganized and degrades. Trachealis muscle becomes more compliant with loss of contractile SMCs. Axial mechanics are governed by collagen structure and longitudinal elastin fibers. Tracheal replacement using tissue engineering technologies offers great potential to improve previously intractable clinical interventions, and interest in this area has increased in recent years. Many engineered airway constructs currently rely on decellularized native tracheas to serve as the scaffold for tissue repair. Yet, mechanical failure leading to airway narrowing and collapse remains a major cause of morbidity and mortality following clinical implantation of decellularized tracheal grafts. To understand better the factors contributing to mechanical failure in vivo, we characterized the histo-mechanical properties of tracheas following two different decellularization protocols, including one that has been used clinically. All decellularized tracheas deviated from native mechanical behavior, which may provide insights into observed in vivo graft failures. We further analyzed protein content by western blot and analyzed microstructure by histological staining and found that the specific method of decellularization resulted in significant differences in the depletion of proteoglycans and degradation of collagens I, II, III, and elastin. Taken together, this work demonstrates that the heterogeneous architecture and mechanical behavior of the trachea is severely compromised by decellularization. Such structural deterioration may contribute to graft failure clinically and limit the potential of decellularized native tracheas as viable long-term orthotopic airway replacements.