Structural mechanism for alteration of collagen gel mechanics by glutaraldehyde crosslinking.
Structural mechanism for alteration of collagen gel mechanics by glutaraldehyde crosslinking.
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DOI：
10.3109/03008207.2011.640760
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发表时间：
2012
影响因子：
2.9
通讯作者：
Holmes JW
中科院分区：
文献类型：
--
作者：
Chandran PL;Paik DC;Holmes JW
体内负载的软胶原组织在衰老和伤口愈合过程中发生交联。植入体内的生物假体组织也通常与戊二醛交联。虽然交联改变了组织的机械性能，但人们对机械变化的性质和潜在的微观结构机制知之甚少。在这项研究中，采用机械、生物化学和模拟相结合的方法来确定交联改变机械性能的微观结构机制。使用的模型胶原组织是各向异性细胞致密胶原凝胶，模型交联剂是单体戊二醛。通过增加戊二醛浓度或增加交联时间，胶原凝胶逐渐交联。在双轴加载实验中，交联的增加产生：（1）对小等双轴预载的应变响应降低，对后续加载的响应几乎没有变化，以及（2）纤维和纤维交叉方向之间的耦合减少。发现赖氨酸消耗数据比收缩温度更能描述机械趋势。使用先前发布的网络模型对增量交联胶原凝胶的双轴加载进行计算模拟。交联表现为原纤维刚度增加或原纤维旋转阻力增加。只有后者产生与实验观察到的相似的机械趋势。将交联表示为原纤维刚度的增加并没有重现纤维和纤维交叉方向之间耦合的减少。该研究的结论是，交联胶原凝胶的机械变化是由原纤维旋转阻力增加的微观结构机制引起的。
Soft collagenous tissues that are loaded in vivo undergo crosslinking during aging and wound healing. Bio-prosthetic tissues implanted in vivo are also commonly crosslinked with glutaraldehyde. While crosslinking changes the mechanical properties of the tissue, the nature of the mechanical changes and the underlying microstructural mechanism is poorly understood. In this study, a combined mechanical, biochemical and simulation approach was employed to identify the microstructural mechanism by which crosslinking alters mechanical properties. The model collagenous tissue used was an anisotropic cell-compacted collagen gel, and the model crosslinking agent was monomeric glutaraldehyde. The collagen gels were incrementally crosslinked by either increasing the glutaraldehyde concentration or by increasing the crosslinking time. In biaxial loading experiments, increased crosslinking produced: (1) decreased strain response to a small equibiaxial preload, with little change in response to subsequent loading, and (2) decreased coupling between the fiber and cross-fiber direction. The mechanical trend was found to be better described by the lysine consumption data than by the shrinkage temperature. The biaxial loading of incrementally-crosslinked collagen gels was simulated computationally with a previously published network model. Crosslinking was represented by increased fibril stiffness or by increased resistance to fibril rotation. Only the latter produced mechanical trends similar to that observed experimentally. Representing crosslinking as increased fibril stiffness did not reproduce the decreased coupling between the fiber and cross-fiber directions. The study concludes that the mechanical changes in crosslinked collagen gels are caused by the microstructural mechanism of increased resistance to fibril rotation.