Structural Analysis of Human Tissue

Background The skin is a large organ that participates in many protective and homeostatic processes. The functions of the skin can be roughly divided into systemic and local ; both are interrelated but relationships are poorly understood and studying them requires a multiscale approach. Particularly, for the local responses that are mediated by activation of proteolytic and signaling pathways such as coagulation and inflammation, the relevant scale corresponds to the micrometer and nanometer dimensions of cells and macromolecules, respectively. There is very little information on the physicochemical characteristics of the skin at these scales. Objective The investigators propose to analyze fresh human skin samples using several up-to-date technologies to obtain parameters on the mechanical, biochemical and structural distribution of the main components of the capillary-tissue unit. Hypothesis/Rationale Our working hypothesis is that both structural components of the dermis, such as glycosaminoglycans, and key mediators of homeostatic pathways, such as the procoagulant tissue factor are not evenly distributed along parallel planes. The investigators further hypothesize that the distribution patterns determine functional and mechanical differences along dermal layers. Methods Using a dermatome, human skin will be dissected along planes parallel to the epidermis into several layers each approximately .0012mm thick. The layers will be analyzed with respect to composition of diffusible proteins and glycosaminoglycans; subjected to high resolution MRI and AFM scanning; and evaluated for swelling rate and equilibrium swelling pressure. Significance This study will provide new information on material characteristics and functional structure of the human skin at resolutions relevant to the macromolecular and cellular processes that mediate local responses to injury and maintain local homeostatic mechanisms. The data will be further processed to obtain realistic parameters that are needed to develop predictive models of the skin capillary tissue unit. These models will bring new and deeper understanding on skin physiology and pathology and will aid in the discovery and testing of new preventive and therapeutic approaches targeting dysfunctions of the local homeostatic balance in the skin. Potentially, by exploiting the versatility of mathematical simulations in the skin model, the findings will also be applicable to other tissue organs.