Computational imaging analysis of glycated fibrin gels reveals aggregated and anisotropic structures

In this article, a computational imaging analysis method is presented for the evaluation of aggregation and anisotropy in both native (unglycated) and glycated fibrin matrix structures. The imaging analysis was used to test the hypothesis that glycated fibrin structures are more aggregated and anisotropic than unglycated (native) fibrin structures. Glycation of fibrinogen, and subsequently fibrin, occurs under normal physiological conditions; however, excess glycation due to disease states such as diabetes can disrupt the fibrin matrix and cause an abnormal structure and function. Studies that elucidate morphological changes in glucose incubated fibrin matrices are necessary to better understand thrombosis, which occurs due to hypercoagulable conditions. In this study, imaging algorithms were designed for the determination of aggregation of fibrin fibers within a matrix as well as preferential orientation (anisotropy) due to glycation. The results showed that glycated fibrin structures displayed an overall higher degree of aggregation and anisotropy as compared to unglycated fibrin structures. However, for glycated fibrin matrices that were polymerized utilizing extended incubation periods representative of physiological plasma glucose conditions, the results showed that fibrin aggregation and anisotropy decreased when compared to unglycated matrices. The algorithms showed that incorporation of the crosslinking agent FXIII into the fibrin matrix was shown to decrease both aggregation and anisotropy. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2191-2198, 2017.