title: Structural mechanism for alteration of collagen gel mechanics by glutaraldehyde crosslinking.
abstract: Soft collagenous tissues that are loaded in vivo undergo crosslinking during aging and wound healing. Bioprosthetic tissues implanted in vivo are also commonly crosslinked with glutaraldehyde (GA). While crosslinking changes the mechanical properties of the tissue, the nature of the mechanical changes and the underlying microstructural mechanism are 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 GA. The collagen gels were incrementally crosslinked by either increasing the GA concentration or 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.
authors: Department of Biomedical Engineering, Columbia University, New York, NY, USA. chandranlp@mail.nih.gov
authors: Preethi L
authors: PL
authors: Chandran
authors: David C
authors: DC
authors: Paik
authors: Jeffrey W
authors: JW
authors: Holmes
mesh_terms: D000818:Animals; D016880:Anisotropy; D001696:Biomechanical Phenomena / Q000187:drug effects; D002417:Cattle; D003094:Collagen / Q000737:chemistry*; D003198:Computer Simulation; D003432:Cross-Linking Reagents / Q000737:chemistry* / Q000494:pharmacology; D005782:Gels / Q000737:chemistry; D005976:Glutaral / Q000737:chemistry* / Q000494:pharmacology; D008954:Models, Biological; D012996:Solutions; D013314:Stress, Mechanical
chemical_list: D003432:Cross-Linking Reagents; D005782:Gels; D012996:Solutions; D003094:Collagen; D005976:Glutaral