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International Cartilage Repair Society (ICRS) Recommended Guidelines for Histological Endpoints for Cartilage Repair Studies in Animal Models and Clinical Trials.

Hoemann C, Kandel R, Roberts S, Saris DB, Creemers L, Mainil-Varlet P, Méthot S, Hollander AP, Buschmann MD - Cartilage (2011)

Bottom Line: 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.Standardized histology methods could improve statistical analyses, help interpret and validate noninvasive imaging outcomes, and permit cross-comparison between studies.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemical Engineering, Institute of Biomedical Engineering, École Polytechnique, Montréal, Quebec, Canada.

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.

No MeSH data available.


Histomorphometry of chondral versus subchondral soft repair tissues. The example is from a 2-month repair of a trochlear full-thickness rabbit knee defect with two 0.9-mm microdrill holes.44 (A) Safranin O–stained trochlear repair tissue, with the “projected tidemark” drawn through the defect area. (B) The chondral repair is cropped separately from the subchondral soft tissue repair for further histomorphometric analysis.
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fig5-1947603510397535: Histomorphometry of chondral versus subchondral soft repair tissues. The example is from a 2-month repair of a trochlear full-thickness rabbit knee defect with two 0.9-mm microdrill holes.44 (A) Safranin O–stained trochlear repair tissue, with the “projected tidemark” drawn through the defect area. (B) The chondral repair is cropped separately from the subchondral soft tissue repair for further histomorphometric analysis.

Mentions: In animal cartilage repair studies, the acute defect may or may not include subchondral bone damage, and during repair, extensive subchondral bone resorption can sometimes occur.38,42,43,120 When there is subchondral bone resorption, and all soft tissue present in the section is evaluated, this will lead to artifactual overestimates of the cartilage repair tissue volume. Likewise, bone overgrowth leads to thinning of the articular layer and the presence of bone in the cartilage defect area.109 To specifically analyze chondral repair tissue versus subchondral repair tissue, a curved “projected tidemark” should be drawn across the defect, using the tidemark of the flanking cartilage, to separate the cartilage repair from the subchondral repair tissue (Fig. 5).


International Cartilage Repair Society (ICRS) Recommended Guidelines for Histological Endpoints for Cartilage Repair Studies in Animal Models and Clinical Trials.

Hoemann C, Kandel R, Roberts S, Saris DB, Creemers L, Mainil-Varlet P, Méthot S, Hollander AP, Buschmann MD - Cartilage (2011)

Histomorphometry of chondral versus subchondral soft repair tissues. The example is from a 2-month repair of a trochlear full-thickness rabbit knee defect with two 0.9-mm microdrill holes.44 (A) Safranin O–stained trochlear repair tissue, with the “projected tidemark” drawn through the defect area. (B) The chondral repair is cropped separately from the subchondral soft tissue repair for further histomorphometric analysis.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4300784&req=5

fig5-1947603510397535: Histomorphometry of chondral versus subchondral soft repair tissues. The example is from a 2-month repair of a trochlear full-thickness rabbit knee defect with two 0.9-mm microdrill holes.44 (A) Safranin O–stained trochlear repair tissue, with the “projected tidemark” drawn through the defect area. (B) The chondral repair is cropped separately from the subchondral soft tissue repair for further histomorphometric analysis.
Mentions: In animal cartilage repair studies, the acute defect may or may not include subchondral bone damage, and during repair, extensive subchondral bone resorption can sometimes occur.38,42,43,120 When there is subchondral bone resorption, and all soft tissue present in the section is evaluated, this will lead to artifactual overestimates of the cartilage repair tissue volume. Likewise, bone overgrowth leads to thinning of the articular layer and the presence of bone in the cartilage defect area.109 To specifically analyze chondral repair tissue versus subchondral repair tissue, a curved “projected tidemark” should be drawn across the defect, using the tidemark of the flanking cartilage, to separate the cartilage repair from the subchondral repair tissue (Fig. 5).

Bottom Line: 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.Standardized histology methods could improve statistical analyses, help interpret and validate noninvasive imaging outcomes, and permit cross-comparison between studies.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemical Engineering, Institute of Biomedical Engineering, École Polytechnique, Montréal, Quebec, Canada.

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.

No MeSH data available.