Nanoindentation of histological specimens: Mapping the elastic properties of soft tissues

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N. Schwarzer Saxonian Institute of Surface Mechanics (SIO), Ummanz 18569, Germany

M.J. Sherratt Tissue Injury and Repair Group, Faculty of Medical and Human Sciences, University of Manchester, Manchester M13 9PT, United Kingdom

R.E.B. Watson Dermatological Sciences Research Group, Faculty of Medical and Human Sciences, University of Manchester, Manchester M13 9PT, United Kingdom

H.K. Graham and A.W. Trafford Unit of Cardiac Physiology, Division of Cardiovascular and Endocrine Sciences, University of Manchester, Manchester M13 9NT, United Kingdom

P.M. Mummery and B. Derby School of Materials, University of Manchester, Manchester M1 7HS, United Kingdom (Received 30 June 2008; accepted 10 October 2008)

Although alterations in the gross mechanical properties of dynamic and compliant tissues have a major impact on human health and morbidity, there are no well-established techniques to characterize the micromechanical properties of tissues such as blood vessels and lungs. We have used nanoindentation to spatially map the micromechanical properties of 5-mm-thick sections of ferret aorta and vena cava and to relate these mechanical properties to the histological distribution of fluorescent elastic fibers. To decouple the effect of the glass substrate on our analysis of the nanoindentation data, we have used the extended Oliver and Pharr method. The elastic modulus of the aorta decreased progressively from 35 MPa in the adventitial (outermost) layer to 8 MPa at the intimal (innermost) layer. In contrast, the vena cava was relatively stiff, with an elastic modulus >30 MPa in both the extracellular matrix-rich adventitial and intimal regions of the vessel. The central, highly cellularized, medial layer of the vena cava, however, had an invariant elastic modulus of 20 MPa. In extracellular matrix-rich regions of the tissue, the elastic modulus, as determined by nanoindentation, was inversely correlated with elastic fiber density. Thus, we show it is possible to distinguish and spatially resolve differences in the micromechanical properties of large arteries and veins, which are related to the tissue microstructure.

I. INTRODUCTION

The need to develop reliable methods for the assessment of tissue elasticity at the microscopic scale is underlined by the impact of cardiovascular and pulmonary disorders on the aging population.1,2 In general, compliant tissues, such as blood vessels, lungs, and skin, become stiffer with age.3 These changes in gross mechanical properties have a profound effect on tissue function and hence morbidity and mortality. In the case of large blood vessels it is now well established that gross a)

Address all correspondence to this author. e-mail: [email protected] DOI: 10.1557/JMR.2009.0130

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J. Mater. Res., Vol. 24, No. 3, Mar 2009 Downloaded: 28 Mar 2015

arterial stiffness, measured in vivo, increases both with age and, separately and excessively, with increased cardiovascular risk factors, including hypertension, diabetes mellitus, and end-stage ren