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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.


Histoprocessing and histomorphometry of large animal defects. The example is taken from a sheep cartilage repair model (6 months repair43). In this unilateral cartilage repair model, the repaired defect (top panels) was decalcified, trimmed at 2 levels in the defect (midproximal and middistal), and stained with Safranin O/Fast Green. Repair tissue above the projected tidemark was cropped using histomorphometric software, and total area (TA) and total stained repair tissue area (TS) were used to determine percentage of Safranin O–stained repair. The contralateral intact condyle was decalcified, trimmed through the middle, and cropped with matching defect width, and total area was used to determine percentage fill of the defect with repair tissue.
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fig3-1947603510397535: Histoprocessing and histomorphometry of large animal defects. The example is taken from a sheep cartilage repair model (6 months repair43). In this unilateral cartilage repair model, the repaired defect (top panels) was decalcified, trimmed at 2 levels in the defect (midproximal and middistal), and stained with Safranin O/Fast Green. Repair tissue above the projected tidemark was cropped using histomorphometric software, and total area (TA) and total stained repair tissue area (TS) were used to determine percentage of Safranin O–stained repair. The contralateral intact condyle was decalcified, trimmed through the middle, and cropped with matching defect width, and total area was used to determine percentage fill of the defect with repair tissue.

Mentions: In animal studies, a rigorous study design includes histological characterization of the acute defect in a separate group of animals (with and without implanted material, also to assess debridement level) and a repair endpoint relevant to the treatment, for example, 2 to 6 months in rabbits and 6 to 12 months in large animals.6,54 As previously recommended,54 a very short repair period, 1 to 7 days postoperatively, can be used to establish implant residency after weightbearing. Insight into biological mechanisms of action can be gleaned after several weeks’ repair in rabbits33,44,52 and several months in sheep or horses.36,42,49,51 In large animal models, histological analyses can be supplemented with analyses of repair tissue biochemistry.40,43,100 In unilateral cartilage repair models, histology of the contralateral joint can be used as a reference for intact cartilage volume (Fig. 3). Intact age-matched osteochondral specimens also serve as useful controls. Detailed recommendations for animal study design are described in another article in this series.101


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)

Histoprocessing and histomorphometry of large animal defects. The example is taken from a sheep cartilage repair model (6 months repair43). In this unilateral cartilage repair model, the repaired defect (top panels) was decalcified, trimmed at 2 levels in the defect (midproximal and middistal), and stained with Safranin O/Fast Green. Repair tissue above the projected tidemark was cropped using histomorphometric software, and total area (TA) and total stained repair tissue area (TS) were used to determine percentage of Safranin O–stained repair. The contralateral intact condyle was decalcified, trimmed through the middle, and cropped with matching defect width, and total area was used to determine percentage fill of the defect with repair tissue.
© Copyright Policy
Related In: Results  -  Collection

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

fig3-1947603510397535: Histoprocessing and histomorphometry of large animal defects. The example is taken from a sheep cartilage repair model (6 months repair43). In this unilateral cartilage repair model, the repaired defect (top panels) was decalcified, trimmed at 2 levels in the defect (midproximal and middistal), and stained with Safranin O/Fast Green. Repair tissue above the projected tidemark was cropped using histomorphometric software, and total area (TA) and total stained repair tissue area (TS) were used to determine percentage of Safranin O–stained repair. The contralateral intact condyle was decalcified, trimmed through the middle, and cropped with matching defect width, and total area was used to determine percentage fill of the defect with repair tissue.
Mentions: In animal studies, a rigorous study design includes histological characterization of the acute defect in a separate group of animals (with and without implanted material, also to assess debridement level) and a repair endpoint relevant to the treatment, for example, 2 to 6 months in rabbits and 6 to 12 months in large animals.6,54 As previously recommended,54 a very short repair period, 1 to 7 days postoperatively, can be used to establish implant residency after weightbearing. Insight into biological mechanisms of action can be gleaned after several weeks’ repair in rabbits33,44,52 and several months in sheep or horses.36,42,49,51 In large animal models, histological analyses can be supplemented with analyses of repair tissue biochemistry.40,43,100 In unilateral cartilage repair models, histology of the contralateral joint can be used as a reference for intact cartilage volume (Fig. 3). Intact age-matched osteochondral specimens also serve as useful controls. Detailed recommendations for animal study design are described in another article in this series.101

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.