Matrix-Induced Autologous Chondrocyte Implantation in Sheep: Objective Assessments Including Confocal Arthroscopy C.W. Jones, 1,2 C. Willers, 2 A. Keogh, 2 D. Smolinski, 1 D. Fick, 2 P.J. Yates, 2 T.B. Kirk, 1 M.H. Zheng 2 1 School of Mechanical Engineering, University of Western Australia, 35 Stirling Highway, Crawley WA, 6009, Australia 2 School of Pathology and Surgery, Department of Orthopaedics, University of Western Australia, 2nd Floor M-block QEII Medical Centre, Nedlands, Perth WA, 6009, Australia Received 18 August 2006; accepted 10 July 2007 Published online 27 September 2007 in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jor.20502 ABSTRACT: The assessment of cartilage repair has largely been limited to macroscopic observation, magnetic resonance imaging (MRI), or destructive biopsy. The aims of this study were to establish an ovine model of articular cartilage injury repair and to examine the efficacy of nondestructive techniques for assessing cartilage regeneration by matrix-induced autologous chondrocyte implantation (MACI). The development of nondestructive assessment techniques facilitates the monitoring of repair treatments in both experimental animal models and human clinical subjects. Defects (Ø 6 mm) were created on the trochlea and medial femoral condyle of 21 sheep randomized into untreated controls or one of two treatment arms: MACI or collagen-only membrane. Each group was divided into 8-, 10-, and 12-week time points. Repair outcomes were examined using laser scanning confocal arthroscopy (LSCA), MRI, histology, macroscopic ICRS grading, and biomechan- ical compression analysis. Interobserver analysis of the randomized blinded scoring of LSCA images validated our scoring protocol. Pearson correlation analysis demonstrated the correlation between LSCA, MRI, and ICRS grading. Testing of overall treatment effect independent of time point revealed significant differences between MACI and control groups for all sites and assessment modalities (Asym Sig < 0.05), except condyle histology. Biomechanical analysis suggests that while MACI tissue may resemble native tissue histologically in the early stages of remodeling, the biomechanical properties remain inferior at least in the short term. This study demonstrates the potential of a multisite sheep model of articular cartilage defect repair and its assessment via nondestructive methods. ß 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:292– 303, 2008 Keywords: cartilage repair; matrix-induced autologous chondrocyte impantation (MACI); confocal microscopy INTRODUCTION It has long been recognized that once damaged, articular cartilage may progress from difficult-to- treat lesions to osteoarthritis. The problems associated in treating the initial lesions have prompted the development of a number of appro- aches, most recently matrix-induced autologous chondrocyte implantation (MACI). 1,2 MACI uti- lizes a type I/III collagen bioscaffold to traffic cultured autologous chondrocytes into the defect, thereby obviating periosteal harvesting and asso- ciated donor site morbidity on the tibia. 2,3 While excellent clinical results have been achieved, significant controversy remains regarding the histological nature of the tissue formed. 4,5 In conjunction with the International Cartilage Repair Society (ICRS), Brittberg and Winalski have standardized the clinical assessment, arthro- scopic evaluation, and magnetic resonance imaging (MRI) of focal cartilage lesions and their repair. 6 In combination with clinical measures, the ICRS system provides an overall assessment of cartilage repair, but provides no histological data. Histolog- ical assessment of cartilage repair tissue distin- guishes between tissue types. 4,7 Previous studies utilized mechanical biopsy to provide tissue sam- ples for histological analysis. 3,4,8,9 A limited amount of data exist regarding the cellular and microstructural nature of MACI repair tissue due to early demonstrations of clinical efficacy and 292 JOURNAL OF ORTHOPAEDIC RESEARCH MARCH 2008 This article includes Supplementary Material available via the Internet at http://www.interscience.wiley.com/jpages/0736- 0266/suppmat. Correspondence to: M.H. Zheng (Telephone: þ61 8 93464050; Fax: þ61 8 93463210; E-mail: minghao.zheng@u- wa.edu.au) ß 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.