title: International Cartilage Repair Society (ICRS) Recommended Guidelines for Histological Endpoints for Cartilage Repair Studies in Animal Models and Clinical Trials.
abstract: Cartilage repair strategies aim to resurface a lesion with osteochondral tissue resembling native cartilage, but a variety of repair tissues are usually observed. Histology is an important structural outcome that could serve as an interim measure of efficacy in randomized controlled clinical studies. The purpose of this article is to propose guidelines for standardized histoprocessing and unbiased evaluation of animal tissues and human biopsies. Methods were compiled from a literature review, and illustrative data were added. In animal models, treatments are usually administered to acute defects created in healthy tissues, and the entire joint can be analyzed at multiple postoperative time points. In human clinical therapy, treatments are applied to developed lesions, and biopsies are obtained, usually from a subset of patients, at a specific time point. In striving to standardize evaluation of structural endpoints in cartilage repair studies, 5 variables should be controlled: 1) location of biopsy/sample section, 2) timing of biopsy/sample recovery, 3) histoprocessing, 4) staining, and 5) blinded evaluation with a proper control group. Histological scores, quantitative histomorphometry of repair tissue thickness, percentage of tissue staining for collagens and glycosaminoglycan, polarized light microscopy for collagen fibril organization, and subchondral bone integration/structure are all relevant outcome measures that can be collected and used to assess the efficacy of novel therapeutics. Standardized histology methods could improve statistical analyses, help interpret and validate noninvasive imaging outcomes, and permit cross-comparison between studies. Currently, there are no suitable substitutes for histology in evaluating repair tissue quality and cartilaginous character.
authors.affiliation: Department of Chemical Engineering, Institute of Biomedical Engineering, École Polytechnique, Montréal, Quebec, Canada.
authors.forename: Caroline
authors.initials: C
authors.lastname: Hoemann
authors.affiliation: BioEngineering of Skeletal Tissues Team, Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Rita
authors.initials: R
authors.lastname: Kandel
authors.affiliation: Spinal Studies & ISTM (Keele University), Robert Jones & Agnes Hunt Orthopaedic Hospital, Oswestry, Shropshire, UK.
authors.forename: Sally
authors.initials: S
authors.lastname: Roberts
authors.affiliation: Department of Orthopaedics, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Daniel B F
authors.initials: DB
authors.lastname: Saris
authors.affiliation: Department of Orthopaedics, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Laura
authors.initials: L
authors.lastname: Creemers
authors.affiliation: Aginko Research, Bern, Switzerland.
authors.forename: Pierre
authors.initials: P
authors.lastname: Mainil-Varlet
authors.affiliation: Piramal Healthcare (Canada), Montréal, Quebec, Canada.
authors.forename: Stephane
authors.initials: S
authors.lastname: Méthot
authors.affiliation: University of Bristol, University Walk, Clifton, Bristol, UK.
authors.forename: Anthony P
authors.initials: AP
authors.lastname: Hollander
authors.affiliation: Department of Chemical Engineering, Institute of Biomedical Engineering, École Polytechnique, Montréal, Quebec, Canada.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Buschmann
keywords: animal models; articular cartilage; biopsy; cartilage repair; collagen type I; collagen type II; fibrocartilage; glycosaminoglycan; histology; polarized light microscopy; subchondral bone; tidemark