The Nanostructure of Implant-Induced Fibrosis

Abstract

Fibrosis or the formation of fibrotic tissue is a product of chronic inflammatory reactions induced by a variety of stimuli and occurs when there is a dysfunction in the wound healing process. This typically ensues following mechanical trauma, tissue injury, surgical intervention or implantation. Quantitative analysis of the developing collagen architecture of fibrotic tissue is an important, but so far almost neglected aspect of wound healing research. Synchrotron X-ray scattering and diffraction techniques are ideally suited for studying structural changes in nanostructured biological tissues. The work presented in this thesis demonstrates the application of a novel technique (microfocus synchrotron scanning Small Angle X-ray Scattering (SAXS) and Wide Angle X-ray Diffraction (WAXD)) in characterizing the presence of collagenous tissue in fibrotic tissue formed surrounding subcutaneous implants. The results of a single (representative) implant type and time point is presented to demonstrate proof-of-principle of the novel technique. This work provides information, for the first time on fibrotic tissue, the nanoscale anisotropy in fibril orientation, the length scale of nanofibrils, the extension of the tropocollagen molecules, and the degree of molecular orientation and crystallinity. These results are, to the best of my knowledge, the first SAXS-model for fibrotic tissue nanostructure and will be the foundation on which subsequent work can be based. It has been shown that, combining microfocus spatial resolution and the quantitative potential of X-ray scattering and diffraction is a suitable approach for characterizing the hierarchical structure of fibrotic tissue in the nanometre and micrometre scales simultaneously.