Image‐based tissue engineering of a total intervertebral disc implant for restoration of function to the rat lumbar spine

Nonbiological total disc replacement is currently being used for the treatment of intervertebral disc (IVD) disease and injury, but these implants are prone to mechanical wear, tear and possible dislodgement. Recently, tissue‐engineered total disc replacement (TE‐TDR) has been investigated as a possible alternative to more fully replicate the native IVD properties. However, the performance of TE‐TDRs has not been studied in the native disc space. In this study, MRI and microcomputed tomography imaging of the rat spine were used to design a collagen (annulus fibrosus)/alginate (nucleus pulposus) TE‐TDR to a high degree of geometric accuracy, with less than 10% difference between TE‐TDR and the native disc dimensions. Image‐based TE‐TDR implants were then inserted into the L4/L5 disc space of athymic rats (n = 5) and maintained for 16 weeks. The disc space was fully or partially maintained in three of five animals and proteoglycan and collagen histology staining was similar in composition to the native disc. In addition, good integration was observed between TE‐TDR and the vertebral bodies, as well as remnant native IVD tissue. Overall, this study provides evidence that TE‐TDR strategies may yield a clinically viable treatment for diseased or injured IVD. Copyright © 2011 John Wiley & Sons, Ltd.

[1]  A. Hiltner,et al.  Hierarchical structure of the intervertebral disc. , 1989, Connective tissue research.

[2]  Observations on Fiber-Forming Collagens in the Anulus Fibrosus , 2000, Spine.

[3]  Jonathan Bard,et al.  COLLAGEN SUBSTRATA FOR STUDIES ON CELL BEHAVIOR , 1972, The Journal of cell biology.

[4]  Hod Lipson,et al.  An optical method for evaluation of geometric fidelity for anatomically shaped tissue-engineered constructs. , 2010, Tissue engineering. Part C, Methods.

[5]  A. Curtis,et al.  Topographical guidance of intervertebral disc cell growth in vitro: towards the development of tissue repair strategies for the anulus fibrosus , 2006, European Spine Journal.

[6]  Y. Xia,et al.  Biochemical (and functional) imaging of articular cartilage. , 2001, Seminars in musculoskeletal radiology.

[7]  L. Bonassar,et al.  Biomechanical and biochemical characterization of composite tissue-engineered intervertebral discs. , 2006, Biomaterials.

[8]  S. Kurtz,et al.  Polyethylene Wear Debris and Long-term Clinical Failure of the Charité Disc Prosthesis: A Study of 4 Patients , 2007, Spine.

[9]  Wan-Ju Li,et al.  Intervertebral disc tissue engineering using a novel hyaluronic acid-nanofibrous scaffold (HANFS) amalgam. , 2008, Tissue engineering. Part A.

[10]  J. Schrooten,et al.  Trabecular bone scaffolding using a biomimetic approach , 2002, Journal of materials science. Materials in medicine.

[11]  M. Hutchinson,et al.  The Burden of Musculoskeletal Diseases in the United States: Prevalance, Societal and Economic Cost, 1st Edition , 2009 .

[12]  S. Kikuchi,et al.  In vivo intradiscal pressure measurement in healthy individuals and in patients with ongoing back problems. , 1999, Spine.

[13]  A. Borthakur,et al.  Assessment of Human Disc Degeneration and Proteoglycan Content Using T1&rgr;-weighted Magnetic Resonance Imaging , 2006, Spine.

[14]  W. Hutton,et al.  Disc Chondrocyte Transplantation in a Canine Model: A Treatment for Degenerated or Damaged Intervertebral Disc , 2003, Spine.

[15]  Marc-Antoine Rousseau,et al.  Ventral Approach to the Lumbar Spine of the Sprague-Dawley Rat , 2004, Lab Animal.

[16]  Broberg Kb,et al.  On the Mechanical Behaviour of Intervertebral Discs , 1983 .

[17]  Y. Xia,et al.  The collagen fibril structure in the superficial zone of articular cartilage by microMRI. , 2009, Osteoarthritis and cartilage.

[18]  J M Pope,et al.  Anisotropy of collagen fibre alignment in bovine cartilage: comparison of polarised light microscopy and spatially resolved diffusion-tensor measurements. , 2008, Osteoarthritis and cartilage.

[19]  Timothy M Wright,et al.  Image-guided tissue engineering of anatomically shaped implants via MRI and micro-CT using injection molding. , 2008, Tissue engineering. Part A.

[20]  S. Kurtz,et al.  Polyethylene wear and rim fracture in total disc arthroplasty. , 2007, The spine journal : official journal of the North American Spine Society.

[21]  Morgan E. Hott,et al.  Fabrication of Tissue Engineered Tympanic Membrane Patches Using Computer‐Aided Design and Injection Molding , 2004, The Laryngoscope.

[22]  Chi-Mun Cheah,et al.  Automatic algorithm for generating complex polyhedral scaffold structures for tissue engineering. , 2004, Tissue engineering.

[23]  F. Marchand,et al.  Investigation of the Laminate Structure of Lumbar Disc Anulus Fibrosus , 1990, Spine.

[24]  D A Jones,et al.  The pathophysiology of the intervertebral disc. , 2001, Joint, bone, spine : revue du rhumatisme.

[25]  N. Langrana,et al.  Role of Ligaments and Facets in Lumbar Spinal Stability , 1995, Spine.

[26]  S D Kuslich,et al.  The tissue origin of low back pain and sciatica: a report of pain response to tissue stimulation during operations on the lumbar spine using local anesthesia. , 1991, The Orthopedic clinics of North America.

[27]  R. Kandel,et al.  Characterization of nucleus pulposus‐like tissue formed in vitro , 2001, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[28]  Charles A Vacanti,et al.  Tissue-Engineered Composites of Anulus Fibrosus and Nucleus Pulposus for Intervertebral Disc Replacement , 2004, Spine.

[29]  R. Soames,et al.  Human intervertebral disc: Structure and function , 1988, The Anatomical record.

[30]  S. Waldman,et al.  Tissue Engineered Nucleus Pulposus Tissue Formed on a Porous Calcium Polyphosphate Substrate , 2004, Spine.

[31]  P. Newman.  The Intervertebral Disc , 1971 .

[32]  R. Derby,et al.  Disc Stimulation and Patterns of Referred Pain , 2002, Spine.

[33]  Brendon M. Baker,et al.  NANOFIBROUS BIOLOGIC LAMINATES REPLICATE THE FORM AND FUNCTION OF THE ANNULUS FIBROSUS , 2009, Nature materials.

[34]  C. Laurencin,et al.  Biphasic scaffold for annulus fibrosus tissue regeneration. , 2008, Biomaterials.

[35]  L. Bonassar,et al.  Self-assembly of aligned tissue-engineered annulus fibrosus and intervertebral disc composite via collagen gel contraction. , 2010, Tissue engineering. Part A.

[36]  D. Eyre,et al.  Biochemical aspects of development and ageing of human lumbar intervertebral discs. , 1977, Rheumatology and rehabilitation.

[37]  Alexander R. Vaccaro,et al.  Lumbar Adjacent Segment Degeneration and Disease After Arthrodesis and Total Disc Arthroplasty , 2008, Spine.

[38]  Hilkka Riihimäki,et al.  Disc Height and Signal Intensity of the Nucleus Pulposus on Magnetic Resonance Imaging as Indicators of Lumbar Disc Degeneration , 2001, Spine.

[39]  Max Aebi,et al.  Immunolocalization of major interstitial collagen types in human lumbar intervertebral discs of various ages , 1998, Virchows Archiv.

[40]  D. Eyre,et al.  Types I and II collagens in intervertebral disc. Interchanging radial distributions in annulus fibrosus. , 1976, The Biochemical journal.

[41]  J. Vital,et al.  Intermediate clinical and radiological results of cervical TDR (Mobi-C®) with up to 2 years of follow-up , 2009, European Spine Journal.

[42]  J L Kelsey,et al.  Epidemiology and Impact of Low-Back Pain , 1980, Spine.

[43]  A. Borthakur,et al.  Proton spin‐lock ratio imaging for quantitation of glycosaminoglycans in articular cartilage , 2003, Journal of magnetic resonance imaging : JMRI.

[44]  C. Hunter,et al.  Developing an alginate/chitosan hybrid fiber scaffold for annulus fibrosus cells. , 2007, Journal of biomedical materials research. Part A.

[45]  J. Mochida,et al.  Effect of Reinsertion of Activated Nucleus Pulposus on Disc Degeneration: An Experimental Study on Various Types of Collagen in Degenerative Discs , 2003, Connective Tissue Research.

[46]  Tony M Keaveny,et al.  Role of Trabecular Microarchitecture in Whole‐Vertebral Body Biomechanical Behavior , 2009, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[47]  Wei Sun,et al.  Computer‐aided tissue engineering: application to biomimetic modelling and design of tissue scaffolds , 2004, Biotechnology and applied biochemistry.

[48]  J. O'Brien,et al.  Immunofluorescent staining for collagen and proteoglycan in normal and scoliotic intervertebral discs. , 1981, The Journal of bone and joint surgery. British volume.

[49]  S. Koh,et al.  Histological changes in aging lumbar intervertebral discs. Their role in protrusions and prolapses. , 1990, The Journal of bone and joint surgery. American volume.

[50]  H. Muir,et al.  Immunochemical localization of collagen types and proteoglycan in pig intervertebral discs. , 1980, Immunology.

[51]  G. Vunjak‐Novakovic,et al.  Porous silk scaffolds can be used for tissue engineering annulus fibrosus , 2007, European Spine Journal.

[52]  N. Kregar-Velikonja,et al.  Nucleus pulposus repair with cultured autologous elastic cartilage derived chondrocytes. , 2004, Cellular & molecular biology letters.

[53]  K. Broberg.  On the Mechanical Behaviour of Intervertebral Discs , 1983, Spine.