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Dissertation from Meniscus to Bone

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Dissertation from Meniscus to Bone DISSERTATION FROM MENISCUS TO BONE: STRUCTURE AND FUNCTION OF HUMAN MENISCAL ENTHESES AND DELETERIOUS EFFECTS OF OSTEOARTHRITIS Submitted by Adam Christopher Abraham Department of Mechanical Engineering In partial fulfillment of the requirements For the Degree of Doctor of Philosophy Colorado State University Fort Collins, Colorado Spring 2013 Doctoral Committee: Advisor: Tammy L. Haut Donahue Kenton R. Kaufman Christian M. Puttlitz Ketul C. Popat Laurie R. Goodrich Copyright by Adam Abraham 2013 All Rights Reserved ABSTRACT FROM MENISCUS TO BONE: STRUCTURE AND FUNCTION OF HUMAN MENISCAL ENTHESES AND DELETERIOUS EFFECTS OF OSTEOARTHRITIS Knee osteoarthritis plagues millions of people in the U.S. alone, yet the mechanisms of initialization are not well understood. Recent work suggests that there are a myriad of potential disease inducing routes that may give rise to this debilitating condition. Understanding and elucidating the potential pathways leading to osteoarthritis may result in novel methods of prevention and/or treatment. Human meniscus are C-shaped fibrocartilaginous structures contained within the diathroidal knee joint, the primary function of which are to provide support and lubrication between the femur and the tibia. Each knee incorporates two menisci, lateral and medial, affixed at the anterior and posterior attachment sites to the tibial plateau. Meniscal attachments, or entheses, are unique graded tissue interfaces comprised of four distinct zones that diffuse longitudinal loads transmitted via hoop stresses of collagen fibrils in the meniscal body. The attachments must remain firmly rooted to the tibial plateau to effectively attenuate joint loads. If the attachments become structurally compromised, either through direct or indirect means, excessive transverse meniscal translation results. Such joint extrusion of the meniscal body is a known precursor to developing osteoarthritis. To date there have been no investigations of integrity of meniscal attachments in the aged arthritic knee. ii A proposed treatment modality for meniscus degeneration is engineered replacements which focus solely on the meniscal body, disregarding the specialized tissue interface. However, the efficacy of these replacements likely remains dependent on restoring the meniscus to bone transition. Previous literature has shown that each meniscal attachment is biochemically and mechanically unique and thus should be independently examined. Therefore, the overall goal of this work is to examine the loading environment of each attachment in both a healthy and injured knee, as well as characterize the structure-function relationship. This knowledge can then be utilized to develop novel preventative strategies in order to deter the onset of osteoarthritis, thereby reducing the burden on individuals as they age. Therefore, the goal of this work was to: • Determine the transverse mechanical properties of the attachment sites and couple with current literature to aid in numerical modeling • Determine the native loading environment for each attachment under physiological and pathlogical loading conditions • Examine the structure and function of the native attachment sites • Examine the deleterious effects of osteoarthritis on the attachment sites. iii ACKNOWLEDGEMENTS This work was supported by the National Institutes of Health, the National Institute for Arthritis and Skin Diseases, the National Institute for Child Health and Human Development, and the National Institute on Aging (R15 AR051906, R01 HD31476, and F31 AG038875). I would like to thank Dr. Julian Wegrzyn, Mayo Clinic, for assistance in preparing cadaver samples and assessment of knee tissue, and Dr. Stavros Thomopoulos, Washington University, for providing custom MATLAB processing software to determine collagen fiber orientation angles. Lastly, I would like to thank all my co-authors and collaborators for various aspects of this work. iv TABLE OF CONTENTS CHAPTER 1: INTRODUCTION ................................................................................................... 1 1.1 The Meniscus ..................................................................................................................... 1 1.1.1 Physiology .................................................................................................................. 2 1.1.2 Pathology .................................................................................................................... 3 1.2 Meniscal Entheses .............................................................................................................. 4 1.2.1 Physiology .................................................................................................................. 5 1.2.2 Pathology .................................................................................................................... 8 1.3 Specific Aims ................................................................................................................... 10 1.4 References ........................................................................................................................ 14 CHAPTER 2: HYPERELASTIC PROPERTIES OF HUMAN MENISCAL ATTACHMENTS18 2.1 Summary .......................................................................................................................... 18 2.2 Introduction ...................................................................................................................... 19 2.3 Materials and Methods ..................................................................................................... 21 2.3.1 Transverse specimen preparation .............................................................................. 21 2.3.2 Transverse test setup ................................................................................................. 22 2.3.3 Transverse testing analysis ....................................................................................... 23 2.3.4 Longitudinal analysis: ............................................................................................... 24 2.3.5 Statistical analysis ..................................................................................................... 26 2.4 Results .............................................................................................................................. 26 2.5 Discussion ........................................................................................................................ 31 2.6 References ........................................................................................................................ 35 CHAPTER 3: INTERNAL PRESSURE OF THE HUMAN MENISCAL ATTACHMENTS DURING PHYSIOLOGICAL AND PATHOLOGICAL LOADING ......................................... 39 3.1 Summary .......................................................................................................................... 39 3.2 Introduction ...................................................................................................................... 40 3.3 Materials and Methods ..................................................................................................... 42 3.4 Results .............................................................................................................................. 44 3.5 Discussion ........................................................................................................................ 46 v 3.6 References ........................................................................................................................ 52 CHAPTER 4: FROM MENISCUS TO BONE: A QUANTITATIVE EVALUATION OF STRUCTURE AND FUNCTION OF THE HUMAN MENISCAL ATTACHMENTS ............. 56 4.1 Summary .......................................................................................................................... 56 4.2 Introduction ...................................................................................................................... 57 4.3 Materials and Methods ..................................................................................................... 59 4.3.1 Sample Preparation ................................................................................................... 59 4.3.2 Histology ................................................................................................................... 60 4.3.3 Collagen Fiber Orientation ....................................................................................... 61 4.3.4 Interdigitation Analysis ............................................................................................. 62 4.3.5 Nano-indentation ....................................................................................................... 64 4.4 Results .............................................................................................................................. 66 4.4.1 Collagen Fiber Orientation ....................................................................................... 66 4.4.2 Interdigitation Analysis ............................................................................................. 68 4.4.3 Nano-Indentation ...................................................................................................... 69 4.5 Discussion ........................................................................................................................ 72 4.6 References .......................................................................................................................
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