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Biomechanics of Human Stratum Corneum: Dry Skin Conditions, Tissue Damage and Alleviation a Dissertation Submitted to the Depar

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Biomechanics of Human Stratum Corneum: Dry Skin Conditions, Tissue Damage and Alleviation a Dissertation Submitted to the Depar BIOMECHANICS OF HUMAN STRATUM CORNEUM: DRY SKIN CONDITIONS, TISSUE DAMAGE AND ALLEVIATION A DISSERTATION SUBMITTED TO THE DEPARTMENT OF MATERIALS SCIENCE AND ENGINEERING AND THE COMMITTEE ON GRADUATE STUDIES OF STANFORD UNIVERSITY IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY Kemal Levi November 2009 © 2010 by Kemal Levi. All Rights Reserved. Re-distributed by Stanford University under license with the author. This work is licensed under a Creative Commons Attribution- Noncommercial 3.0 United States License. http://creativecommons.org/licenses/by-nc/3.0/us/ This dissertation is online at: http://purl.stanford.edu/cb644mw1707 ii I certify that I have read this dissertation and that, in my opinion, it is fully adequate in scope and quality as a dissertation for the degree of Doctor of Philosophy. Reinhold Dauskardt, Primary Adviser I certify that I have read this dissertation and that, in my opinion, it is fully adequate in scope and quality as a dissertation for the degree of Doctor of Philosophy. Sarah Heilshorn I certify that I have read this dissertation and that, in my opinion, it is fully adequate in scope and quality as a dissertation for the degree of Doctor of Philosophy. William Nix Approved for the Stanford University Committee on Graduate Studies. Patricia J. Gumport, Vice Provost Graduate Education This signature page was generated electronically upon submission of this dissertation in electronic format. An original signed hard copy of the signature page is on file in University Archives. iii Abstract The outermost layer of human skin, the stratum corneum (SC), is subject daily to variable ambient moisture and temperature conditions as well as application of potentially damaging cleansing agents. The inevitable results of these exposures are “tightness” of the skin which is directly related to the buildup of tensile residual drying stresses in the SC layer. In this work, we first describe the application of the substrate curvature technique to quantitatively measure the magnitude of these stresses and their relationship to selected drying environments and times. The SC drying stresses were observed to be very sensitive to the relative humidity and temperature of the drying environment as well as harshness of the chemical treatment. There was a strong correlation with the SC drying stresses and the chemical potential of water in the drying environment. The evolution of drying stresses in SC is discussed in relation to the effects of hydration and damage caused by chemical treatments on the underlying SC structure. We also describe the application of the substrate curvature technique to characterize stresses in occlusive topical coatings. We then extend the substrate curvature technique to measure the combined effects of the coating applied to human stratum corneum (SC) where the overall drying stresses may have contributions from the coating, the SC and the interaction of the coating with the SC. We show how these separate contributions in the coating and SC layers can be differentiated. Using this methodology, we characterize the effect of a range of moisturizing treatments on the drying stresses in human stratum corneum. Following moisturizer treatment, the SC was observed to have distinctive stress profiles with drying time depending on the effectiveness of the treatment. The stress values of specimens treated with the humectant moisturizers were observed to increase and stabilize after a few hours in the drying environment where they remained relatively constant until the end of exposure to the drying environment whereas the stress values of specimens treated with the emollient treatments were observed to rise rapidly to a peak stress value and relax to a final iv stress value. The effect of moisturizing treatments on the SC drying stresses was rationalized in terms of SC water loss and the chemical state of the SC components. Finally, we employ a fracture mechanics approach to understand the implications of the drying stresses in SC as a mechanical driving force for damage propagation (e.g. cracking and chapping) in the tissue. The crack driving force G was found for several cracking configurations and compared with the intercellular delamination energy, Gc, which is a property of the tissue that provides a measure of the resistance to cracking. Using this approach, we demonstrate how damaging treatments enhance and moisturizing treatments alleviate the propensity for dry skin damage. v Acknowledgements When I was a child, my grandmother used to tell me that time passes really quickly. At that point in my life, hating to go to school every day, time seemed to be stuck somewhere. When academic work became much more interesting in college, my grandmother’s statement became all too true – time was passing by very quickly. During my undergraduate work at Washington and Lee University, I had the great opportunity to work one to one with a professor whose specialty was on polymer rheology. At that time, I started falling in love with the concept of research. It almost became a hobby, a lifestyle for me by my senior year in college. As a very junior researcher, I was fascinated by all research opportunities out there and decided to pursue graduate research at one of the best programs in the country. When I stepped into the good old Peterson building five years ago, I knew that this was not going to be an easy experience. Coming from a liberal arts school, I was at a disadvantage compared to my peers coming from the best engineering programs across the country and the world. While struggling with my classes and bad news related to my dad’s deteriorating health condition, there was only one thing that made me happy – my research project. This was almost the ideal project for someone who once wanted to get into the medical school but chose interdisciplinary research instead. I’d like to thank my advisor, Prof. Reinhold Dauskardt, for offering me a position in the skin research program. I feel very lucky to have had Prof. Dauskardt as an advisor. He kept me in balance in bad times and good times and prepared me for real life. I greatly appreciate all the time and commitment he invested in my academic and personal growth. Aside from the many things he has taught me, I will never forget his great sense of humor. I am looking forward to our future work and interactions. I would like to recognize many of the outstanding professors and educators at Stanford with whom I had the opportunity to interact. I would like to thank Professors William Nix, Sarah Heilshorn, Marc Levenston and Geoffrey vi Gurtner for their great input in my research and for donating their time & effort to serve in my defense committee. Throughout my time at Stanford, I had the privilege of interacting with an exceptional group of students and colleagues. I mentored extremely bright and talented eight undergraduate students in various projects. I would like to thank Rob Weber, Sumil Thapa, Victoria Hsiao, Alice Kwan, James Do, Allison Rhines, Andrea Tang and Zack Feinberg for their significant contribution to the stratum corneum research. To my highly motivated, bright colleagues, thank you all for your continuous support, close collaboration, fun weekly meetings and good laughs. Thank you- Ruiliang Jia, Ani Kamer, Taek-Soo Kim, Mark Oliver, Andrew Kearney, Max Gage, Alex Hsing, Vitali Brandt, Fernando Novoa, Yusuke Matsuda and Jeff Yang. Stanford is a great place, almost like heaven with all the palm trees and scenery around, yet sanity is not possible without family and good friends as the grounding center. I would like to thank my wife, Marina, for keeping me social and sane, inspiring me to grow as a person, giving me attention and love, babysitting me often and providing outstanding ideas for my research as a fellow engineer. What you have done means a lot to me and I promise to be a better husband after I graduate. I would like to also thank my dear friends Ahmet Altay and Emre Oto for being there for me in our shared trials, tribulations, and successes at Stanford. With the fond memories of our long discussions and cooking blunders, including a few garlic attacks, thank you - Ahmet and Emre - for your enduring friendship. Finally, I would like to dedicate this thesis to my wonderful parents, who have raised me to be the person I am today and strive to be. My dad will always continue to live in my life, and I will never forget his teachings. Mom & dad – you have been with me every step of the way, through good times and bad. Thank you for the unconditional love, guidance, and support, instilling confidence in me to pursue anything I put my mind to and helping me to succeed. Thank you for everything. I love you! vii Table of Contents Abstract iv Acknowledgements vi Table of Contents vii List of Tables xii List of Figures xiii Chapter 1 Introduction 1 1.1 Background and Significance 1 1.2 Biomechanics of Dry Skin and Tissue Damage 2 1.3 In-Vivo Complexities and Relevance 5 1.4 Stratum Corneum Structure 6 1.5 Prior Stratum Corneum Research 8 1.6 Synopsis 12 1.7 References 14 Chapter 2 Theoretical Mechanics Background 17 2.1 Griffith Energy Balance 18 2.2 The Stress Intensity Factor 22 2.3 Equivalence of G and K 24 2.4 Fracture in Film - Substrate Systems 25 2.5 Crack Driving Force of SC 29 2.6 Conclusion 30 2.7 References 30 Chapter 3 Experimental Procedures 32 3.1 Isolation of Human Stratum Corneum 32 3.2 Micro - Tension 33 3.3 Substrate Curvature 35 3.4 Double Cantilever Beam Fabrication 38 3.5 Delamination
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