Biochemical changes caused by decellularization may compromise mechanical integrity of tracheal scaffolds

Biochemical changes caused by decellularization may compromise mechanical integrity of tracheal scaffolds
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DOI:
10.1016/j.actbio.2012.10.004
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发表时间:
2013-02-01
期刊:
影响因子:
9.7
通讯作者:
Wall, I. B.
Wall, I. B.
中科院分区:
工程技术1区
文献类型:
--
作者:
Partington, L.;Mordan, N. J.;Wall, I. B.

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组织工程气道已经取得了临床成功,但仍然存在关于短期生物力学性能损失的担忧,需要支架。本研究调查了化学-酶促脱细胞化对气管生化特性的影响,这些特性对于细胞附着和血管化(纤连蛋白和层粘连蛋白)和软骨基质稳态(II型胶原和糖胺聚糖(GAG))以及生物力学状态至关重要。天然气管用作对照,与去细胞化平行储存在磷酸盐缓冲盐水(PBS)中的NDC气管用作时间匹配的对照。脱细胞去除了大部分细胞,但软骨细胞和DNA在25个循环后保留。纤连蛋白保留在整个固有层和层粘连蛋白在基底膜。观察到DNA沿ECM纤维沿着积聚。在脱细胞组织中观察到可溶性胶原蛋白的下降。即使在PBS对照组织中,从20个周期开始,软骨环的GAG含量也有所减少(p < 0.05),但去细胞化导致的损失最大(p < 0.01)。抗张强度在整个过程中下降,但仅在稍后的时间点显著。数据表明,GAG的大幅降低可能导致生物气管机械完整性的丧失。克服导致软骨基质平衡失衡的结构变化对于优化临床益处是必要的,从而使生物气管能够广泛使用。(C)2012 Acta Materialia Inc.由Elsevier Ltd.出版。保留所有权利。
Tissue-engineered airways have achieved clinical success, but concerns remain about short-term loss of biomechanical properties, necessitating a stent. This study investigated the effect of chemical-enzymatic decellularization on biochemical properties of trachea important for cell attachment and vascularization (fibronectin and laminin) and cartilage matrix homeostasis (type II collagen and glycosaminoglycans (GAG)), as well as biomechanical status. Native trachea was used as a control, and NDC trachea stored in phosphate buffered saline (PBS) in parallel to decellularization was used as a time-matched control. Decellularization removed most cells, but chondrocytes and DNA remained after 25 cycles. Fibronectin was retained throughout the lamina propria and laminin at basement membranes. DNA accumulation along ECM fibres was seen. A decline in soluble collagen was observed in decellularized tissue. GAG content of cartilage rings was reduced, even in PBS control tissue from 20 cycles onwards (p < 0.05), but decellularization caused the greatest loss (p < 0.01). Tensile strength declined throughout the process, but was significant only at later time points. The data demonstrate that the substantial reduction in GAG might contribute to loss of mechanical integrity of biotracheas. Overcoming structural changes that cause an imbalance in cartilage matrix equilibrium will be necessary to optimize clinical benefit, enabling widespread use of biotracheas. (C) 2012 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.