The Biomechanics of the Inter-Lamellar Matrix and the Lamellae During Progression to Lumbar Disc Herniation: Which is the Weakest Structure? JAVAD TAVAKOLI , 1 DHARA B. AMIN, 1 BRIAN J. C. FREEMAN, 2,3,4 and JOHN J. COSTI 1 1 Biomechanics and Implants Research Group, Medical Device Research Institute, College of Science and Engineering, Flinders University, GPO Box 2100, Adelaide, SA 5001, Australia; 2 Department of Spinal Surgery, Royal Adelaide Hospital, Adelaide, Australia; 3 Centre for Orthopaedic and Trauma Research, Adelaide Health & Medical Sciences, University of Adelaide, Adelaide, Australia; and 4 South Australian Health & Medical Research Institute, Adelaide, Australia (Received 23 January 2018; accepted 18 May 2018) Associate Editor Andreas Anayiotos oversaw the review of this article. Abstract—While microstructural observations have im- proved our understanding of possible pathways of herniation progression, no studies have measured the mechanical failure properties of the inter-lamellar matrix (ILM), nor of the adjacent lamellae during progression to herniation. The aim of this study was to employ multiscale, biomechanical and microstructural techniques to evaluate the effects of progres- sive induced herniation on the ILM and lamellae in control, pre-herniated and herniated discs (N = 7), using 2 year-old ovine spines. Pre-herniated and herniated (experimental) groups were subjected to macroscopic compression while held in flexion (13°), before micro-mechanical testing. Micro- tensile testing of the ILM and the lamella from anterior and posterolateral regions was performed in radial and circum- ferential directions to measure failure stress, modulus, and toughness in all three groups. The failure stress of the ILM was significantly lower for both experimental groups com- pared to control in each of radial and circumferential loading directions in the posterolateral region (p < 0.032). Within each experimental group in both loading directions, the ILM failure stress was significantly lower by 36% (pre-herniation), and 59% (herniation), compared to the lamella (p < 0.029). In pre-herniated compared to control discs, microstructural imaging revealed significant tissue stretching and change in orientation (p < 0.003), resulting in a loss of distinction between respective lamellae and ILM boundaries. Keywords—Biomechanics, Interlamellar matrix, Lumbar disc herniation, Microstructure, Multiscale, Lamellae, Ovine model, Failure stress. INTRODUCTION The prevalence of lumbar disc herniation is esti- mated at 3–5%. 26 Herniated lumbar discs and resul- tant radiculopathy have resulted in almost 15 million office-based physicians visits per year, creating a financial burden on society exceeding US$50 billion in the US annually. 13 Approximately 300,000 lumbar discectomies are performed each year in the USA, making it the most common procedure performed by spine and neurosurgeons. 17 Disruption of the annulus fibrosus (AF) is mani- fested as circumferential and radial tears, and rim lesions. 21 These tears are present after cumulative 34 or sudden pre-herniation 2,33 events that lead to hernia- tion. Circumferential tears are common and were observed in cadaver discs from the teenage years. 36 It is thought that delamination of adjacent lamellae are the first steps towards the development of circumferential tears, which can lead to early disc degeneration. 7 The failure mechanism of circumferential tears is believed to arise from high inter-lamellar shear stresses, which lead to propagation of these tears. 16 Delamination is a known failure mechanism of composite, laminate structures, suggesting that the region at highest risk of failure initiation is at the boundary between lamellae, which is referred to as the inter-lamellar matrix (ILM). 29 Circumferential disruption of the ILM has been observed as a likely pathway for the nucleus material to follow during herniation. 33,34,37–39 Microstructural observations have revealed new in- sights into AF tissue disruption during herniation, 32,35 as well as the delamination strength of isolated AF samples of the ILM. 9 While these studies have im- proved our understanding of where herniation may Address correspondence to John J. Costi, Biomechanics and Implants Research Group, Medical Device Research Institute, Col- lege of Science and Engineering, Flinders University, GPO Box 2100, Adelaide, SA 5001, Australia. Electronic mail: john.costi@flinders. edu.au Annals of Biomedical Engineering (Ó 2018) https://doi.org/10.1007/s10439-018-2056-0 Ó 2018 Biomedical Engineering Society