Spine Bioengineering Laboratory
      Email: james.iatridis@uvm.edu
 

Researching Intervertebral Disc Mechanobiology and Tissue Engineering.

 

 
Spine Bioengineering workgroup, Summer 2008:
front row: Mark Freedman, James, Kristin Funabashi
back row: Karrie Godburn, Ben Walter, Art Michalek, Ana Barbir, Devina Purmessur

lab group spring summer 2008

Research Goals:

The general research area of the Spine Bioengineering Laboratory is in the area of soft-tissue bioengineering and the relationship between mechanical events and the biological response of living tissues. The primary research focus is in the area of spine and intervertebral disc bioengineering. Understanding the relationship between the mechanical, electrical, and chemical fields in the living tissue and the biosynthetic response of cells is necessary for early detection of degenerative disc disease and successful repair of the intervertebral disc.

Personnel

James C. Iatridis (Head)
Karrie Godburn, BS (Lab Manager)
Devina Purmessur, PhD
Art Michalek, MS
Ana Barbir, MS
Benjamin A Walter, BS
Mark Freedman
Kristin Funabashi


On campus collaborators:
Ian A.F. Stokes: Ortho/Rehab
Robert Monsey: Ortho/Rehab
David Aronsson: Ortho/Rehab
Jeffrey Laible: Civil & Environmental Eng
Martin Krag: Ortho/Rehab
Junru Wu: Physics
Helene Langevin: Neurology
Off campus collaborators:
Mauro Alini:  AO Research Institute, Davos, Switzerland
Keita Ito: AO Research Institute, Davos, Switzerland
John Antoniou: McGill University, Montreal, Canada
Tapas Goswami: McGill University, Montreal, Canada

Peter Roughley: McGill University, Montreal, Canada
Rocky Tuan: Cartilage Biology & Orthopaedics Branch, NIAMS, NIH

Job Postings

Selected Recent Publications (contact  james.iatridis@uvm.edu for access to .pdf files of papers)

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Photo Gallery

Alumni                       Time in the Lab     Current Position
Cynthia Lee, PhD                  2002-2005                      Senior Scientist - Cartilage Technologies , DePuy Biologics
Diana Hidalgo, MS,               2004-2005                                         
Delphine Perie-Curnier, PhD  2003-2004                      Research Scientist, Laboratoire de Biomecanique, Toulouse cedex, France
Lisa Hovey, B.S.                  2004
Julia Owen, B.S.                  2003-2004                      PhD Student, Bioengineering, UC Berkeley
Heather Boepple, B.S.          2005                             Tissue Regeneration, Inc.
David Ryan, B.S.                  2003-2004                     Research Technician (Lab Manager), Orthopaedic Mechanobiology Lab, University of Maryland, College Park
Brennan Schaeffer, B.S.       2003
Suzanne Kavy, B.S.,           2003                               M Eng student, Transportation, Cornell University
Laura Albert, B.A.               2003
David Korda, B.S.               2003-2006                        MS Student, Mechanical Engineering, Cornell University
Anna Snarski, B.A.            2004-2006                        DVM Student, Purdue University
Kazunori Masuoka, M.D.  
2005                                Dept. of Ortho Surg, National Defense Medical College, Saitama, Japan
J Stinnett-Donnelly, M.S.  
2004-2006                         MD Student, University of Vermont
Jeffrey J. MacLean, M.S.   1999-2006                        
MD Student, University of Vermont
John Jack Costi, Ph.D.     
2005-2006                          Research Faculty, Repatriation General Hospital & Flinders University, Adelaide, Australia
Karin Wuertz, Ph.D.         
2006-2007                          Research faculty, University of Zurich, Switzerland
Jake Lubinsky, M.S.        
2006-2007
Alon Lai, Ph.D.                 2008                                   Post-doctoral Fellow, Hong Kong Polytechnic University
Casey Korecki, Ph.D.       2003-2008                           Post-doctoral Fellow, NIAMS, NIH, Bethesda, MD



Research Grants


Low Back Pain

Seventy to 85% of all people have back pain at some time in life, with the annual prevalence of back pain ranging from 15-45%. Back pain is the most frequent cause of activity limitation in people below 45 years and is a common reason for visiting a health care provider.   Symptoms are most common in middle-aged adults, with back pain equally common in men and women; however, back pain secondary to disc disorders is more common in men.


Intervertebral Disc Anatomy

The intervertebral disc is a complex structure that transmits and distributes large loads on the spine while providing flexibility. Located on the radial periphery of the intervertebral disc, the anulus fibrosus (AF) is believed to experience a combination of compressive, tensile, and shear stresses during weight-bearing and intervertebral joint motion. Failure of this composite structure is a frequent clinical finding believed to contribute to the etiology of disc degeneration and other symptomatic disc disorders. The central nucleus pulposus (NP) comprises almost half of the non-degenerate intervertebral disc and is predominantly water in a matrix of proteoglycans, collagen, and other matrix proteins.
 
Diagram of human lumbar intervertebral disc and dissection of cylindrical-shaped specimens of anulus fibrosus. Axial and radial correspond to orientations parallel and perpendicular to the vertebral body line of the spine, respectively. Annulus layers are roughly 0.1-0.3 mm thick with approximately 40 fiber bundles per layer alternating at roughly +/- 30 degrees. Photograph of normal (left) and degenerative human L2-3 intervertebral discs.


Mechanical and Electrical Properties of Human Intervertebral Disc

Function, failure, and remodeling of the intervertebral disc are all related to the stress and strain fields in the tissue and may be calculated using finite element models with accurate material properties, realistic geometry and appropriate boundary conditions.
 
Material properties range from the predominantly viscous vitreous humor of the eye to the predominantly elastic spinal motion segment. You can also compare the range of viscoelastic properties from the nucleus pulposus to the anulus fibrosus.

See reference:
Iatridis JC, Weidenbaum M, Setton LA, Mow VC: Is the nucleus pulposus a solid or fluid? Mechanical behaviors of the nucleus pulposus of the human intervertebral disc, Spine  21:1174-1184, 1996

This was the first comprehensive study to investigate shear material properties of the anulus fibrosus and tested the hypotheses that these shear mechanical properties of the anulus are affected by amplitude and frequency of shearing, applied compressive stress, and degenerative state of the tissue. The figure on the right exhibits the effect of increasing compressive stress on the dynamic shear material properties of the anulus.

See reference:
Iatridis JC, Kumar S, Foster RJ, Mow VC: Shear mechanical properties of human lumbar anulus fibrosus, J Orthop Res, 17:732-737, 1999

The goal of this study was to investigate the influence of the changes in tissue structure and composition on the electrokinetic behavior of intervertebral disc tissues.  It was found that the streaming potential of the anulus fibrosus depended on the degenerative grade of the discs and on the specimen orientation in which the fluid flows. The dynamic streaming potential responses of anulus fibrosus (shown on right) were sensitive to the degeneration of the disc. The alteration of streaming potential reflects the changes in tissue composition and structure with degeneration.

See reference:
Gu WY, Mao XG, Rawlins BA, Iatridis JC, Foster RJ, Sun DN, Weidenbaum M, Mow VC: Streaming potential of human lumbar anulus fibrosus in anisotropic and affected by disc degeneration, J Biomechanics, 32: 1177-1182, 1999


Effects of Compression on Intervertebral Disc Propertiesx-ray image

A rat tail model was used to test the hypothesis that chronically applied compressive forces and immobilization will cause changes in mechanical properties and composition of rat tail intervertebral discs in a manner similar to that seen in human spinal disc degeneration. Results indicated there were decreases in disc thickness, axial compliance, and angular laxity and an increase in proteoglycan content of the loaded discs. The radiographs below depict the methods for measuring intervertebral disc thickness and stiffness in vivo.

See reference:
Iatridis JC, Mente PL, Stokes IAF, Aronsson DD, Alini M: Compression induced changes to intervertebral discs properties in a rat tail model, Spine, 24:996-1002, 1999



Poroelastic and Chemical Electric (PEACE) Model of Healthy and Degenerated Intervertebral Discsfea mesh

Degenerative changes to the intervertebral disc are commonly implicated in low back pain and result in significant losses of water content and proteoglycans, particularly in the central nucleus pulposus. The loss of fixed charges (associated with the proteoglycans) will influence mechanical and electrical fields within the disc. The objectives of this study were to apply a poroelastic and chemical electric (PEACE) finite element model to a 2-D slice of intervertebral disc and investigate the influence of fixed charge density (FCD) and applied electrical potential on fluid transport, pressurization, and streaming potential.

The PEACE finite element model was written using MATLAB software based on the models of Gu et al 1993, and Simon et al 1996. Geometry was taken as a thin horizontal slice of disc (5 mm thick) with idealized horizontal plane dimensions characteristic of a human lumbar disc. Boundary conditions included impermeable, insulated, frictionless, and rigid top and bottom surfaces so that there was no vertical flow. This could represent the conditions at the mid-elevation of a disc. The mechano-electrochemical material coefficients were taken from the literature. Values for healthy and degenerated fixed charge density distributions were taken from experimentally determined values for 26 year old and 74 year old discs from Urban & Holm 1986. The healthy distribution had values for FCD approximately 0.15M at the edge of the disc and approximately 0.3 M at the center of the disc. The u-w solution was obtained for: 1) a swelling & compression test where the disc was equilibrated in 0.2M NaCl followed by a step compressive stress of 0.2 MPa; and 2) an applied electrical potential on the boundaries where point A was set to 0 mV and point B was set to twice the natural potential (i.e., -10.75 and –6.3 mV for healthy and degenerated discs, respectively).

The Figure below demonstrates the model prediction of the hydraulic pressurization of the healthy intervertebral disc slice at equilibrum. Significant alterations in the load carrying mechanism from healthy to degenerated discs were determined with the healthy disc carries most of the loading through fluid stress (pressurization). The degenerated disc, on the other hand, carries significantly more stresses in the solid matrix which could predispose the increased matrix damage. Alterations in the disc fixed charge density from healthy to degenerated will affect load carrying mechanisms, fluid content, and electrical potential response. These differences have implications for disc failure, disc nutrition, modulation of cellular activities, and tissue remodeling.

See reference:
Iatridis JC, Laible JP, Krag MH: Influence of fixed charge density magnitude and distribution on the intervertebral disc: Applications of a poroelastic and chemical electric model, J Biomechanical Engineering, 125:12-24, 2003  


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