Journal of Biomechanical Science and Engineering Researches on Biomechanical Properties and Models of Peripheral Nerves
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Bulletin of the JSME Vol.12, No.1, 2017 Journal of Biomechanical Science and Engineering 【Review Paper】 Researches on biomechanical properties and models of peripheral nerves - a review Ming-Shaung JU*, Chou-Ching K. LIN** and Cheng-Tao CHANG* *Department of Mechanical Engineering, National Cheng Kung University 1 University Road, Tainan 701, Taiwan (R.O.C.) E-mail: [email protected] **Department of Neurology College of Medicine and University Hospital National Cheng Kung University 1 University Road, Tainan 701, Taiwan (R.O.C.) Received: 14 December 2016; Revised: 11 February 2017; Accepted: 6 March 2017 Abstract The biomechanics of peripheral nerve plays an important role in physiology of the healthy and pathology of the diseased such as the diabetic neuropathy, the cauda equine compression and the carpal tunnel syndrome. The other application is recent development of neural prostheses. The goal of this paper is to review researches done by members of Taiwanese Society of Biomechanics on the biomechanics of peripheral nerves in the past two decades. First, a brief introduction of the anatomy of peripheral nerve is given. Then experiment designs and mechanical models for testing the nerves are presented. The material properties ranged from linear elastic to nonlinear visco-elastic and scales ranged from organ level to tissue level are reviewed. Implications of these studies to clinical problems will be addressed and the challenges and future perspective on biomechanics of peripheral nerve are discussed. Key words: Biomechanics, Peripheral nerve, Review, Diabetic mellitus, Cauda equine 1. Introduction Nervous system plays an important role in the human body it can coordinate voluntary and involuntary actions of other tissues and sub-systems. The nervous system can be divided into central nervous system (CNS) and peripheral nervous system (PNS) (Preston and Wilson, 2012). The CNS contains the neurons of the brain and spinal cord and it is the integrative and decision-making part of the nervous system. The PNS refers to parts of the nervous system outside the brain and spinal cord. It is a complicated, extensive network of nerves that collects sensory information and conveys it to the CNS for processing. Nerve tissue is mainly composed of neurons and supporting cells. The neuron can transmit action potential rapidly from one area of the body to the next. It can be divided into four zones as: cell body, dendrite, axon and nerve terminal. Depending on distribution in CNS and PNS the supporting cells have different types. The supporting cells of the PNS are Schwann cells that form myelin to wrap axon of the neuron. In case the peripheral nerve is injured by trauma or neuropathy, the distal zone would be degenerated and the proximal zone may be regenerated to recover the peripheral nerve function. If the affected area is not cared properly it may become a neuroma that causes long-term nerve injury. Drug and physical therapy were commonly utilized to help the injured nerve to recover and regeneration. Diabetic neuropathy, carpal tunnel syndrome, and nerve trauma are common symptoms of nerve injuries in Taiwan and all over the world. The biomechanical properties of peripheral nerves are important factors of the repair and regeneration process of the nerve after injury (Sunderland, 1978). The goal of this paper is to review the researches done by members of Taiwanese Society of Biomechanics on the biomechanics of peripheral nerves in the past two decades. As a background, first, a brief introduction of the anatomy of peripheral nerve is given. Then special experiments designed for in vitro and in situ tests of the nerves are presented. The material properties of peripheral nerves with complexity from linear elastic to nonlinear visco-elastic and scales from organ level to tissue level are also introduced with methods of parameter estimation. Implications of these biomechanics studies to clinical problems will be addressed and the challenges and future perspective on biomechanics of peripheral nerve are discussed. Paper No.16-00678 J-STAGE Advance Publication date: 23 March, 2017 [DOI: 10.1299/jbse.16-00678] © 2017 The Japan Society of Mechanical Engineers 1 Ju, Lin and Chang, Journal of Biomechanical Science and Engineering, Vol.12, No.1 (2017) 2. Anatomy of Peripheral Nerves The axons within the peripheral nerve are long extension of their cell bodies located in the dorsal root ganglia, autonomic ganglia, or the ventral horn of the spinal cord or brain stem (Topp and Boyd, 2006). The axons are insulated from each other, bundled together, and protected by three main connective tissue layers, namely the endoneurium, the perineurium, and the epineurium (Fig. 1). The axon, myelin sheath, and endoneurial components are bundled by a perineurium layer to form a nerve fascicle. Several fascicles are held together by the epineurial connective tissue layer to form a peripheral nerve (Preston and Wilson, 2012). Within the endoneurium, nerve fibers are composed of myelinated and un-myelinated neuron axons. Each fascicle has motor, sensory, and autonomic nerve fibers or just one kind of them. Each myelinated axon is wrapped tightly by a Schwann cell for multiple turns to form a myelin sheath. At node of Ranvier two Schwann cells are separated. Unmyelinated axons are bundled together and enveloped by Schwann cell cytoplasm and plasma membrane. The endoneurium fills the inner space of each fascicle and it is consisted of fibroblasts, type I & II collagen fibrils, few mast cells and macrophages. The collagen fibrils are arranged longitudinally and with a diameter less than 50 nm. It forms an endoneurial tube that contains endoneurial fluid which provides inner pressure of the fascicle. If a fascicle is cut transversely, the inner components of the endoneurium are protruded to a mushroom shape. This pressure can make the fascicle stiffer (Lundborg, 2004; Spencer et al., 1975). The nerve fibers surrounded by the endoneurium have slightly undulating shape such that they can be stretched by a small initial tensile force on the nerve. The endoneurium can resist the outer tensile force but its stiffness is less than that of perineurium and the nerve fibers can be easily compressed and extended by external load (Sunderland, 1978). Fig 1. The ultra-structure and organization of a peripheral nerve. Perineurium is the thinnest but most dense layer of the three connective tissues. It protects the nerve fibers and maintains the inner pressure and stiffness of the fascicle. Fifteen layers of flat perineurial cells are tightly connected to each other within the perineurium. Type I & II collagen fibrils and elastic fibers are filled within the intersection of each layer. Most of these fibers are longitudinally and the rest are cross-over distributed to form dense network. The collagen fibril layers and perineurial cells provided the nerve enough strength against external load. Depending on the size of the fascicle the thickness of the perineurium ranged between of 1.3 to 100 m (Sunderland and Bradley, 1961). The epineurium is an areolar connective tissue to hold nerve fascicles together. For nerves having multiple fascicles, the epineurium is divided into epifascicular epineurium and interfascicular epineurium (Sunderland, 1978; Topp and Boyd, 2006). The epineurium is a loose structure to keep the nerve soft and serves as a buffer barrier to protect the inner fascicles against external load. The epineurium contained type I & III collagen fibrils, elastic fibers, mast cells, and adipose tissue. Most of the collagen fibers were longitudinally distributed and the rest were formed as randomly cross-over arrays. These fibrils were thicker than the other two connective tissues. Similar to many organs, the peripheral nerves are highly vascularized tissues. Transmission of action potential and axonal transport are supported by nutrients supplied by capillary vessels. Intra-neural blood vessels are abundant in all layers of the nerve, forming a pattern of longitudinally oriented vessels (Lundborg, 2004). Based on location the blood vessels can be classified as extrinsic and intrinsic vessels. The extrinsic vessels support vascular plexus superficial and deep layers of the connective tissues. Intrinsic vessels are distributed inside the epineurium, perineurium, and endoneurium. Epineurial arterioles form an anastomotic network running longitudinally within the epifascicular [DOI: 10.1299/jbse.16-00678] © 2017 The Japan Society of Mechanical Engineers 2 Ju, Lin and Chang, Journal of Biomechanical Science and Engineering, Vol.12, No.1 (2017) epineurium and the interfascicular epineurium. Perforating arterioles intersect the perineurium at oblique angles. Peri-neurial arterioles slightly regulated intra-fascicular blood flow with poorly developed smooth muscles. Within the endoneurium the arterioles turn into large-diameter, longitudinally oriented capillaries. After that, venules return blood to the venous system. Generally, the inter-neural blood vessels including arterioles and venules could be defined as vasa nervorum (Moore and Dalley, 2006; Rohkamm, 2014). The peripheral nerves are endured to various mechanical loads under normal physiological conditions imposed by human movements and postures, e.g., the nerve is subjected to tensile stress when joint motion caused elongation of the nerve bed. The carpal tunnel syndrome, a frequently encountered chronic peripheral neuropathy, and neuropathy caused by diabetes mellitus are due to long-term compression of the nerves (Main et al., 2011). When diabetic nerves are subjected to long-term compression, the blood vessels will be damaged followed by injury of the nerve fibers (Dyck et al., 1986; Dyck and Giannini, 1996). 3. Experiment and biomechanical model of peripheral nerves as a whole According to the types of mechanical loads on the peripheral nerves in vivo, two kinds of mechanical tests have been designed, namely, the axial tensile test and transverse compression. The geometry of peripheral nerve is a long string with diameter 1.19 0.10mm for rabbits, rats and 1.2-5mm for human. Therefore, customized testing devices have to be designed to performed in vitro or in vivo tests.