Comprehensive analysis of translational osteochondral repair: Focus on the histological assessment.

Articular cartilage guarantees for an optimal functioning of diarthrodial joints by providing a gliding surface for smooth articulation, weight distribution, and shock absorbing while the subchondral bone plays a crucial role in its biomechanical and nutritive support. Both tissues together form the osteochondral unit. The structural assessment of the osteochondral unit is now considered the key standard procedure for evaluating articular cartilage repair in translational animal models. The aim of this review is to give a detailed overview of the different methods for a comprehensive evaluation of osteochondral repair. The main focus is on the histological assessment as the gold standard, together with immunohistochemistry, and polarized light microscopy. Additionally, standards of macroscopic, non-destructive imaging such as high resolution MRI and micro-CT, biochemical, and molecular biological evaluations are addressed. Potential pitfalls of analysis are outlined. A second focus is to suggest recommendations for osteochondral evaluation.

[1]  P. Bullough,et al.  Histological Assessment of Cartilage Repair: A Report by the Histology Endpoint Committee of the International Cartilage Repair Society (ICRS) , 2003, The Journal of bone and joint surgery. American volume.

[2]  H. Madry,et al.  Effect of open wedge high tibial osteotomy on the lateral tibiofemoral compartment in sheep. Part II: standard and overcorrection do not cause articular cartilage degeneration , 2014, Knee Surgery, Sports Traumatology, Arthroscopy.

[3]  H J Mankin,et al.  Articular cartilage: tissue design and chondrocyte-matrix interactions. , 1998, Instructional course lectures.

[4]  Yang Xia,et al.  Quantitative Determination of Morphological and Territorial Structures of Articular Cartilage from Both Perpendicular and Parallel Sections by Polarized Light Microscopy , 2011, Connective tissue research.

[5]  J. Arokoski,et al.  Specimen preparation and quantification of collagen birefringence in unstained sections of articular cartilage using image analysis and polarizing light microscopy , 1997, The Histochemical Journal.

[6]  E B Hunziker,et al.  Quantitative structural organization of normal adult human articular cartilage. , 2002, Osteoarthritis and cartilage.

[7]  D. Burr,et al.  Anatomy and physiology of the mineralized tissues: role in the pathogenesis of osteoarthrosis. , 2004, Osteoarthritis and cartilage.

[8]  J Feng,et al.  The biomechanical, morphologic, and histochemical properties of the costal cartilages in children with pectus excavatum. , 2001, Journal of pediatric surgery.

[9]  J. Steadman,et al.  Early Events in Cartilage Repair After Subchondral Bone Microfracture , 2003, Clinical orthopaedics and related research.

[10]  A. Cruz,et al.  The OARSI histopathology initiative - recommendations for histological assessments of osteoarthritis in the horse. , 2010, Osteoarthritis and cartilage.

[11]  C. Little,et al.  The OARSI histopathology initiative - recommendations for histological assessments of osteoarthritis in the mouse. , 2010, Osteoarthritis and cartilage.

[12]  B. Snyder,et al.  Contrast agent electrostatic attraction rather than repulsion to glycosaminoglycans affords a greater contrast uptake ratio and improved quantitative CT imaging in cartilage. , 2011, Osteoarthritis and cartilage.

[13]  Ewald Moser,et al.  7‐T MR—from research to clinical applications? , 2012, NMR in biomedicine.

[14]  H. Madry,et al.  Overexpression of human IGF-I via direct rAAV-mediated gene transfer improves the early repair of articular cartilage defects in vivo , 2014, Gene Therapy.

[15]  M. Shive,et al.  Chitosan-glycerol phosphate/blood implants improve hyaline cartilage repair in ovine microfracture defects. , 2005, The Journal of bone and joint surgery. American volume.

[16]  J. Sun,et al.  Bone marrow stimulation induces greater chondrogenesis in trochlear vs condylar cartilage defects in skeletally mature rabbits. , 2013, Osteoarthritis and cartilage.

[17]  Richard Kasch,et al.  Semiquantitative analysis of ECM molecules in the different cartilage layers in early and advanced osteoarthritis of the knee joint. , 2012, Histology and histopathology.

[18]  R. Wright,et al.  Correlation Between Magnetic Resonance Imaging and Clinical Outcomes After Cartilage Repair Surgery in the Knee , 2013, The American journal of sports medicine.

[19]  S. Nehrer,et al.  Critical‐size defect induces unicompartmental osteoarthritis in a stable ovine knee , 2012, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[20]  R. Aspden India ink and cartilage. , 2011, Osteoarthritis and cartilage.

[21]  Wouter J A Dhert,et al.  Single-Stage Cell-Based Cartilage Regeneration Using a Combination of Chondrons and Mesenchymal Stromal Cells , 2013, The American journal of sports medicine.

[22]  J. Pelletier,et al.  Cartilage, bone and synovial histomorphometry in animal models of osteoarthritis. , 2010, Osteoarthritis and cartilage.

[23]  Joseph M. Mansour,et al.  Mesenchymal Cell-Based Repair of Large Full Thickness Defects of Articular Cartilage , 1994 .

[24]  R. Warren,et al.  Acceleration of cartilage repair by genetically modified chondrocytes over expressing bone morphogenetic protein‐7 , 2003, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[25]  D. Kohn,et al.  Failed cartilage repair for early osteoarthritis defects: a biochemical, histological and immunohistochemical analysis of the repair tissue after treatment with marrow-stimulation techniques , 2012, Knee Surgery, Sports Traumatology, Arthroscopy.

[26]  D. Saris,et al.  The correlation and reproducibility of histological scoring systems in cartilage repair. , 2002, Tissue engineering.

[27]  Ali Guermazi,et al.  State of the Art: MR Imaging after Knee Cartilage Repair Surgery. , 2015, Radiology.

[28]  C. Archer,et al.  Cartilage integration: evaluation of the reasons for failure of integration during cartilage repair. A review. , 2008, European cells & materials.

[29]  R. E. Outerbridge THE ETIOLOGY OF CHONDROMALACIA PATELLAE , 1961 .

[30]  Sharmila Majumdar,et al.  Comparison of quantitative imaging of cartilage for osteoarthritis: T2, T1rho, dGEMRIC and contrast-enhanced computed tomography. , 2009, Magnetic resonance imaging.

[31]  Zhongping Chen,et al.  Topographical variations in the polarization sensitivity of articular cartilage as determined by polarization-sensitive optical coherence tomography and polarized light microscopy. , 2008, Journal of biomedical optics.

[32]  V. Krenn,et al.  Stellenwert der histologischen Diagnostik der Synovialkrankheiten , 2009, Der Orthopade.

[33]  Henning Madry,et al.  The basic science of the subchondral bone , 2010, Knee Surgery, Sports Traumatology, Arthroscopy.

[34]  J. Ellermann,et al.  Surgical induction, histological evaluation, and MRI identification of cartilage necrosis in the distal femur in goats to model early lesions of osteochondrosis. , 2015, Osteoarthritis and cartilage.

[35]  Oliver Bieri,et al.  23Na MR imaging at 7 T after knee matrix-associated autologous chondrocyte transplantation preliminary results. , 2010, Radiology.

[36]  Siegfried Trattnig,et al.  Three-Dimensional Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) Score Assessed With an Isotropic Three-Dimensional True Fast Imaging With Steady-State Precession Sequence at 3.0 Tesla , 2009, Investigative radiology.

[37]  D. Zurakowski,et al.  Acceleration of articular cartilage repair by combined gene transfer of human insulin-like growth factor I and fibroblast growth factor-2 in vivo , 2010, Archives of Orthopaedic and Trauma Surgery.

[38]  G. Bydder,et al.  Ultrashort-echo time MR imaging of the patella with bicomponent analysis: correlation with histopathologic and polarized light microscopic findings. , 2012, Radiology.

[39]  G. Im,et al.  Repair of cartilage defect in the rabbit with cultured mesenchymal stem cells from bone marrow. , 2001, The Journal of bone and joint surgery. British volume.

[40]  S. O’Driscoll Current Concepts Review - The Healing and Regeneration of Articular Cartilage* , 1998 .

[41]  H. Kokkonen,et al.  Correlation of Subchondral Bone Density and Structure from Plain Radiographs with Micro Computed Tomography Ex Vivo , 2015, Annals of Biomedical Engineering.

[42]  E. Hunziker,et al.  Repair of Partial-Thickness Defects in Articular Cartilage: Cell Recruitment from the Synovial Membrane* , 1996, The Journal of bone and joint surgery. American volume.

[43]  W. Remmele,et al.  [Recommendation for uniform definition of an immunoreactive score (IRS) for immunohistochemical estrogen receptor detection (ER-ICA) in breast cancer tissue]. , 1987, Der Pathologe.

[44]  Laurence Vico,et al.  High-Resolution Three-Dimensional Micro-Computed Tomography Detects Bone Loss and Changes in Trabecular Architecture Early: Comparison with DEXA and Bone Histomorphometry in a Rat Model of Disuse Osteoporosis , 2002, Investigative radiology.

[45]  F. Eckstein,et al.  MR imaging of cartilage and its repair in the knee - a review , 2009, European Radiology.

[46]  M. Szychlinska,et al.  Histochemistry as a Unique Approach for Investigating Normal and Osteoarthritic Cartilage , 2014, European journal of histochemistry : EJH.

[47]  Y. Shafieyan,et al.  Diffusion of MRI and CT contrast agents in articular cartilage under static compression. , 2014, Biophysical journal.

[48]  N. Broom,et al.  A functional-morphological study of the tidemark region of articular cartilage maintained in a non-viable physiological condition. , 1982, Journal of anatomy.

[49]  E B Hunziker,et al.  Articular cartilage repair: basic science and clinical progress. A review of the current status and prospects. , 2002, Osteoarthritis and cartilage.

[50]  J. Pelletier,et al.  The OARSI histopathology initiative - recommendations for histological assessments of osteoarthritis in the dog. , 2010, Osteoarthritis and cartilage.

[51]  S. Goldstein,et al.  The direct examination of three‐dimensional bone architecture in vitro by computed tomography , 1989, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[52]  A. Nixon,et al.  Enhanced early chondrogenesis in articular defects following arthroscopic mesenchymal stem cell implantation in an equine model , 2007, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[53]  D Kohn,et al.  Alterations of the subchondral bone in osteochondral repair--translational data and clinical evidence. , 2013, European cells & materials.

[54]  Ferris M. Pfeiffer,et al.  Animal models of cartilage repair , 2014, Bone & joint research.

[55]  C. Rorabeck,et al.  Increased damage to type II collagen in osteoarthritic articular cartilage detected by a new immunoassay. , 1994, The Journal of clinical investigation.

[56]  D. Zurakowski,et al.  2D and 3D MOCART scoring systems assessed by 9.4 T high-field MRI correlate with elementary and complex histological scoring systems in a translational model of osteochondral repair. , 2014, Osteoarthritis and cartilage.

[57]  G. Knutsen,et al.  Arthroscopic assessment of cartilage repair: a validation study of 2 scoring systems. , 2005, Arthroscopy : the journal of arthroscopic & related surgery : official publication of the Arthroscopy Association of North America and the International Arthroscopy Association.

[58]  M. Buschmann,et al.  Characterization of Subchondral Bone Repair for Marrow-Stimulated Chondral Defects and Its Relationship to Articular Cartilage Resurfacing , 2011, The American journal of sports medicine.

[59]  H. Madry,et al.  Improved repair of chondral and osteochondral defects in the ovine trochlea compared with the medial condyle , 2013, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[60]  R. Rossi,et al.  Intra- and inter-observer reliability of ten major histological scoring systems used for the evaluation of in vivo cartilage repair , 2015, Knee Surgery, Sports Traumatology, Arthroscopy.

[61]  H. Madry,et al.  Complex and elementary histological scoring systems for articular cartilage repair. , 2015, Histology and histopathology.

[62]  M. Drezner,et al.  Bone histomorphometry: Standardization of nomenclature, symbols, and units: Report of the asbmr histomorphometry nomenclature committee , 1987, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[63]  Y. Henrotin,et al.  Osteochondral plate angiogenesis: a new treatment target in osteoarthritis. , 2011, Joint, bone, spine : revue du rhumatisme.

[64]  Jukka S Jurvelin,et al.  Practical considerations in the use of polarized light microscopy in the analysis of the collagen network in articular cartilage , 2008, Microscopy research and technique.

[65]  G. Lust,et al.  Insulin-like growth factor-I enhances cell-based repair of articular cartilage. , 2002, The Journal of bone and joint surgery. British volume.

[66]  N. Südkamp,et al.  Comparison of arthroscopic and open assessment of size and grade of cartilage defects of the knee. , 2011, Arthroscopy : the journal of arthroscopic & related surgery : official publication of the Arthroscopy Association of North America and the International Arthroscopy Association.

[67]  P. Cozzone,et al.  Fast imaging strategies for mouse kidney perfusion measurement with pseudocontinuous arterial spin labeling (pCASL) at ultra high magnetic field (11.75 tesla) , 2015, Journal of magnetic resonance imaging : JMRI.

[68]  E. Radin,et al.  Microfractures and microcracks in subchondral bone: are they relevant to osteoarthrosis? , 2003, Rheumatic diseases clinics of North America.

[69]  Ralph Müller,et al.  Guidelines for assessment of bone microstructure in rodents using micro–computed tomography , 2010, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[70]  H. Kokkonen,et al.  Diffusion and near-equilibrium distribution of MRI and CT contrast agents in articular cartilage , 2009, Physics in medicine and biology.

[71]  M. Li,et al.  Selection of Suitable Reference Genes for Normalization of Quantitative Real-Time PCR in Cartilage Tissue Injury and Repair in Rabbits , 2012, International journal of molecular sciences.

[72]  Ewald Moser,et al.  Ultra-high-field magnetic resonance: Why and when? , 2010, World journal of radiology.

[73]  S W O'Driscoll,et al.  Durability of regenerated articular cartilage produced by free autogenous periosteal grafts in major full-thickness defects in joint surfaces under the influence of continuous passive motion. A follow-up report at one year. , 1988, The Journal of bone and joint surgery. American volume.

[74]  E. Morris,et al.  The Effect of Recombinant Human Bone Morphogenetic Protein-2 (rhBMP-2) on the Healing of Full-Thickness Defects of Articular Cartilage* , 1997, The Journal of bone and joint surgery. American volume.

[75]  M. Menger,et al.  PTH [1-34]-induced alterations of the subchondral bone provoke early osteoarthritis. , 2014, Osteoarthritis and cartilage.

[76]  J. Kanis,et al.  Standardized nomenclature, symbols, and units for bone histomorphometry: A 2012 update of the report of the ASBMR Histomorphometry Nomenclature Committee , 2013, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[77]  D. Saris,et al.  International Cartilage Repair Society (ICRS) and Oswestry macroscopic cartilage evaluation scores validated for use in Autologous Chondrocyte Implantation (ACI) and microfracture. , 2007, Osteoarthritis and cartilage.

[78]  H. Madry,et al.  Advancement of the Subchondral Bone Plate in Translational Models of Osteochondral Repair: Implications for Tissue Engineering Approaches. , 2015, Tissue engineering. Part B, Reviews.

[79]  D. Zurakowski,et al.  Reliability, reproducibility, and validation of five major histological scoring systems for experimental articular cartilage repair in the rabbit model. , 2012, Tissue engineering. Part C, Methods.

[80]  R. Kandel,et al.  A New Histology Scoring System for the Assessment of the Quality of Human Cartilage Repair: ICRS II , 2010, The American journal of sports medicine.

[81]  T. Dufresne,et al.  Quantitative imaging of proteoglycan in cartilage using a gadolinium probe and microCT. , 2006, Osteoarthritis and cartilage.

[82]  Andoni P. Toms,et al.  Accuracy of magnetic resonance imaging, magnetic resonance arthrography and computed tomography for the detection of chondral lesions of the knee , 2012, Knee Surgery, Sports Traumatology, Arthroscopy.

[83]  K. Pritzker,et al.  The OARSI histopathology initiative - recommendations for histological assessments of osteoarthritis in the rabbit. , 2010, Osteoarthritis and cartilage.

[84]  R. Salter,et al.  The chondrogenic potential of free autogenous periosteal grafts for biological resurfacing of major full-thickness defects in joint surfaces under the influence of continuous passive motion. An experimental investigation in the rabbit. , 1986, The Journal of bone and joint surgery. American volume.

[85]  V. Goldberg,et al.  Principles of tissue engineered regeneration of skeletal tissues. , 1999, Clinical orthopaedics and related research.

[86]  M. Menger,et al.  Enamel matrix derivative inhibits proteoglycan production and articular cartilage repair, delays the restoration of the subchondral bone and induces changes of the synovial membrane in a lapine osteochondral defect model in vivo , 2014, Journal of tissue engineering and regenerative medicine.

[87]  P. Rüegsegger,et al.  A microtomographic system for the nondestructive evaluation of bone architecture , 2006, Calcified Tissue International.

[88]  E B Hunziker,et al.  Ultrastructure of adult human articular cartilage matrix after cryotechnical processing , 1997, Microscopy research and technique.

[89]  N. Südkamp,et al.  Long-term Outcomes After First-Generation Autologous Chondrocyte Implantation for Cartilage Defects of the Knee , 2014, The American journal of sports medicine.

[90]  M. Spector,et al.  Histologic analysis of tissue after failed cartilage repair procedures. , 1999, Clinical orthopaedics and related research.

[91]  D. Zurakowski,et al.  Transplanted articular chondrocytes co-overexpressing IGF-I and FGF-2 stimulate cartilage repair in vivo , 2011, Knee Surgery, Sports Traumatology, Arthroscopy.

[92]  R. Reddy,et al.  High Resolution T1ρ Mapping of In Vivo Human Knee Cartilage at 7T , 2014, PloS one.

[93]  C. Mattea,et al.  Feasibility of high-resolution one-dimensional relaxation imaging at low magnetic field using a single-sided NMR scanner applied to articular cartilage. , 2015, Journal of magnetic resonance.

[94]  I. Kiviranta,et al.  Cell–tissue interactions in osteoarthritic human hip joint articular cartilage , 2014, Connective tissue research.

[95]  Yang Xia,et al.  Quantitative zonal differentiation of articular cartilage by microscopic magnetic resonance imaging, polarized light microscopy, and Fourier‐transform infrared imaging , 2013, Microscopy research and technique.

[96]  D. Kohn,et al.  Temporal and spatial migration pattern of the subchondral bone plate in a rabbit osteochondral defect model. , 2012, Osteoarthritis and cartilage.

[97]  W. Stanish,et al.  Chondroinduction Is the Main Cartilage Repair Response to Microfracture and Microfracture With BST-CarGel , 2015, The American journal of sports medicine.

[98]  L. Begum,et al.  Autologous chondrocyte implantation drives early chondrogenesis and organized repair in extensive full‐ and partial‐thickness cartilage defects in an equine model , 2011, Journal of Orthopaedic Research.

[99]  G. De Falco,et al.  Imaging of articular cartilage: current concepts , 2014, Joints.

[100]  F. Noyes,et al.  A system for grading articular cartilage lesions at arthroscopy , 1989, The American journal of sports medicine.

[101]  M J Lammi,et al.  Contrast agent enhanced pQCT of articular cartilage , 2007, Physics in medicine and biology.

[102]  M. G. Krukemeyer,et al.  Das differenzialdiagnostische Spektrum der Synovialitis , 2008, Zeitschrift für Rheumatologie.

[103]  H. Madry,et al.  Small Subchondral Drill Holes Improve Marrow Stimulation of Articular Cartilage Defects , 2014, The American journal of sports medicine.

[104]  Michael D. Buschmann,et al.  Preclinical Studies for Cartilage Repair , 2011, Cartilage.

[105]  P. Rüegsegger,et al.  Morphometric analysis of noninvasively assessed bone biopsies: comparison of high-resolution computed tomography and histologic sections. , 1996, Bone.

[106]  A. Bücker,et al.  High resolution MRI imaging at 9.4 Tesla of the osteochondral unit in a translational model of articular cartilage repair , 2015, BMC Musculoskeletal Disorders.

[107]  C. Chichester,et al.  Articular collagen degradation in the Hulth-Telhag model of osteoarthritis. , 1999, Osteoarthritis and cartilage.

[108]  Jörg Haller,et al.  Magnetic resonance observation of cartilage repair tissue (MOCART) for the evaluation of autologous chondrocyte transplantation: determination of interobserver variability and correlation to clinical outcome after 2 years. , 2006, European journal of radiology.

[109]  Wei Ouyang,et al.  Drilling and microfracture lead to different bone structure and necrosis during bone‐marrow stimulation for cartilage repair , 2009, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[110]  A. Nixon,et al.  Enhanced repair of extensive articular defects by insulin‐like growth factor‐I‐laden fibrin composites , 1999, Journal of Orthopaedic Research.

[111]  V. Goldberg,et al.  A semiquantitative scale for histologic grading of articular cartilage repair. , 1992, Acta anatomica.

[112]  U. Wolfram,et al.  Effect of Subchondral Drilling on the Microarchitecture of Subchondral Bone , 2012, The American journal of sports medicine.

[113]  A. Barbero,et al.  Visual histological grading system for the evaluation of in vitro-generated neocartilage. , 2006, Tissue engineering.

[114]  A. Bücker,et al.  Experimental scoring systems for macroscopic articular cartilage repair correlate with the MOCART score assessed by a high-field MRI at 9.4 T--comparative evaluation of five macroscopic scoring systems in a large animal cartilage defect model. , 2012, Osteoarthritis and cartilage.

[115]  T. Kamarul,et al.  The effects of staged intra-articular injection of cultured autologous mesenchymal stromal cells on the repair of damaged cartilage: a pilot study in caprine model , 2013, Arthritis Research & Therapy.

[116]  J. Steadman,et al.  Arthroscopic subchondral bone plate microfracture technique augments healing of large chondral defects in the radial carpal bone and medial femoral condyle of horses. , 1999, Veterinary surgery : VS.

[117]  N. Südkamp,et al.  Long-term T2 and Qualitative MRI Morphology After First-Generation Knee Autologous Chondrocyte Implantation , 2014, The American journal of sports medicine.

[118]  H. Dorfman,et al.  Biochemical and metabolic abnormalities in articular cartilage from osteo-arthritic human hips. II. Correlation of morphology with biochemical and metabolic data. , 1971, The Journal of bone and joint surgery. American volume.

[119]  W. Richter,et al.  Local application of a collagen type I/hyaluronate matrix and growth and differentiation factor 5 influences the closure of osteochondral defects in a minipig model by enchondral ossification , 2006, Growth factors.

[120]  D Mainard,et al.  Cartilage repair using new polysaccharidic biomaterials: macroscopic, histological and biochemical approaches in a rat model of cartilage defect. , 2003, Osteoarthritis and cartilage.

[121]  D. Loeuille,et al.  In vivo high-resolution MRI (7T) of femoro-tibial cartilage changes in the rat anterior cruciate ligament transection model of osteoarthritis: a cross-sectional study. , 2010, Rheumatology.

[122]  Jan Sedlacik,et al.  Susceptibility weighted imaging at ultra high magnetic field strengths: Theoretical considerations and experimental results , 2008, Magnetic resonance in medicine.

[123]  Y. Tabata,et al.  Regeneration of Defects in Articular Cartilage in Rat Knee Joints by CCN2 (Connective Tissue Growth Factor) , 2004, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[124]  D. Zurakowski,et al.  Parathyroid hormone [1-34] improves articular cartilage surface architecture and integration and subchondral bone reconstitution in osteochondral defects in vivo. , 2013, Osteoarthritis and cartilage.