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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.


Appearance of human 2-mm-diameter biopsy obtained with a Jamshidi 11-gauge needle (A, C) and corresponding decalcified Safranin O–stained paraffin section (B, D). Samples were obtained ex vivo with an ethics-approved protocol from the same lateral condyle (nonlesional area) obtained after total knee arthroplasty (74-year-old female). (A and B) A biopsy cored perpendicular to the surface and (C and D) a biopsy cored deliberately at an oblique angle to the surface are shown. Both biopsies were initially 6 mm long, but the subchondral bone was missing from the oblique biopsy prior to histoprocessing (C). Part of the subchondral bone in the perpendicular biopsy (B) was lost during histoprocessing.
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fig2-1947603510397535: Appearance of human 2-mm-diameter biopsy obtained with a Jamshidi 11-gauge needle (A, C) and corresponding decalcified Safranin O–stained paraffin section (B, D). Samples were obtained ex vivo with an ethics-approved protocol from the same lateral condyle (nonlesional area) obtained after total knee arthroplasty (74-year-old female). (A and B) A biopsy cored perpendicular to the surface and (C and D) a biopsy cored deliberately at an oblique angle to the surface are shown. Both biopsies were initially 6 mm long, but the subchondral bone was missing from the oblique biopsy prior to histoprocessing (C). Part of the subchondral bone in the perpendicular biopsy (B) was lost during histoprocessing.

Mentions: A clinical biopsy is obtained during a second-look arthroscopy. During the procedure, it is essential to document and score the general intra-articular findings. Utilization of a validated scoring system is recommended; a number of studies have used the ICRS macroscopic score.56,61,70,71,74,83,99 The Outerbridge classification has also been used to describe articular cartilage repair; however, the score was originally designed to describe a cartilage injury and therefore is not recommended. The defect size, integration, and repair aspect as well as the biopsy procedure and location and intra-articular findings should be documented using a video-capture system. Documentation of the biopsy site should be sufficiently detailed to permit comparison of histology with other joint parameters (i.e., meniscal status, alignment). Osteochondral biopsies can be taken with a 1.8- to 2.3-mm inner-diameter bone biopsy needle (up to 3-mm nominal outer diameter) such as Jamshidi (11 gauge, Cardinal Health, Dublin, OH),59,71 Manatech (Stoke-on-Trent, England), Trapsystem (11 gauge, MD TECH, Gainesville, FL),72 or Giebel (Karl Storz, Tuttlingen, Germany),83 and video capture can be used to document the biopsy site. The technique may be first practiced ex vivo with animal joints or on human cadaveric specimens. Biopsies should be taken from the estimated geometric center of the initial lesion to minimize the possibility of collecting adjacent (normal or degraded) cartilage and should be as perpendicular as possible to the bone.96 The needle is inserted by very carefully placing the needle and gently tapping with a mallet approximately 1 cm deep in order to obtain several millimeters of subchondral bone and is twisted clockwise and counterclockwise (10 times each way) to core the sample and break the biopsy from the subchondral bone, using a technique similar to the one used for retrieval of osteochondral grafts during a mosaicplasty procedure. The biopsy is extruded backwards through the needle with a fitted wire pressing on the bone core to avoid damaging the soft repair tissue at the opposite end. The biopsy should be photodocumented with a size marker or ruler59 (Fig. 2) and processed immediately (see below, Histoprocessing). All surgical details including problems with biopsy retrieval, time into fixative, and a schematic of the location in the defect should be documented and transferred to the histologist. For some lesion sites, biopsies can only be collected oblique to the cartilage surface, and these may need to go deeper to collect subchondral bone (Figs. 2C and 2D). Also, despite best efforts by the surgeon to extract a biopsy from the middle of the repaired lesion, it is possible that the biopsy is retrieved outside the lesion. It is suggested that the blinded observers flag any biopsies with features suggestive of a nonrepresentative biopsy such as a well-formed tidemark or normal-appearing hyaline cartilage with a lamina splendens. In some repair samples, especially those slightly delaminated, the twisting motion used to extract the biopsy can lead to the bone or surface becoming separated from the cartilage repair in the biopsy specimen. Broken samples have previously been eliminated from some analyses61,68; however, the separate pieces can be processed together to obtain a subset of histological and histomorphometric values, which may reduce bias. Some features can still be scored even if the biopsy is not complete.


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)

Appearance of human 2-mm-diameter biopsy obtained with a Jamshidi 11-gauge needle (A, C) and corresponding decalcified Safranin O–stained paraffin section (B, D). Samples were obtained ex vivo with an ethics-approved protocol from the same lateral condyle (nonlesional area) obtained after total knee arthroplasty (74-year-old female). (A and B) A biopsy cored perpendicular to the surface and (C and D) a biopsy cored deliberately at an oblique angle to the surface are shown. Both biopsies were initially 6 mm long, but the subchondral bone was missing from the oblique biopsy prior to histoprocessing (C). Part of the subchondral bone in the perpendicular biopsy (B) was lost during histoprocessing.
© Copyright Policy
Related In: Results  -  Collection

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

fig2-1947603510397535: Appearance of human 2-mm-diameter biopsy obtained with a Jamshidi 11-gauge needle (A, C) and corresponding decalcified Safranin O–stained paraffin section (B, D). Samples were obtained ex vivo with an ethics-approved protocol from the same lateral condyle (nonlesional area) obtained after total knee arthroplasty (74-year-old female). (A and B) A biopsy cored perpendicular to the surface and (C and D) a biopsy cored deliberately at an oblique angle to the surface are shown. Both biopsies were initially 6 mm long, but the subchondral bone was missing from the oblique biopsy prior to histoprocessing (C). Part of the subchondral bone in the perpendicular biopsy (B) was lost during histoprocessing.
Mentions: A clinical biopsy is obtained during a second-look arthroscopy. During the procedure, it is essential to document and score the general intra-articular findings. Utilization of a validated scoring system is recommended; a number of studies have used the ICRS macroscopic score.56,61,70,71,74,83,99 The Outerbridge classification has also been used to describe articular cartilage repair; however, the score was originally designed to describe a cartilage injury and therefore is not recommended. The defect size, integration, and repair aspect as well as the biopsy procedure and location and intra-articular findings should be documented using a video-capture system. Documentation of the biopsy site should be sufficiently detailed to permit comparison of histology with other joint parameters (i.e., meniscal status, alignment). Osteochondral biopsies can be taken with a 1.8- to 2.3-mm inner-diameter bone biopsy needle (up to 3-mm nominal outer diameter) such as Jamshidi (11 gauge, Cardinal Health, Dublin, OH),59,71 Manatech (Stoke-on-Trent, England), Trapsystem (11 gauge, MD TECH, Gainesville, FL),72 or Giebel (Karl Storz, Tuttlingen, Germany),83 and video capture can be used to document the biopsy site. The technique may be first practiced ex vivo with animal joints or on human cadaveric specimens. Biopsies should be taken from the estimated geometric center of the initial lesion to minimize the possibility of collecting adjacent (normal or degraded) cartilage and should be as perpendicular as possible to the bone.96 The needle is inserted by very carefully placing the needle and gently tapping with a mallet approximately 1 cm deep in order to obtain several millimeters of subchondral bone and is twisted clockwise and counterclockwise (10 times each way) to core the sample and break the biopsy from the subchondral bone, using a technique similar to the one used for retrieval of osteochondral grafts during a mosaicplasty procedure. The biopsy is extruded backwards through the needle with a fitted wire pressing on the bone core to avoid damaging the soft repair tissue at the opposite end. The biopsy should be photodocumented with a size marker or ruler59 (Fig. 2) and processed immediately (see below, Histoprocessing). All surgical details including problems with biopsy retrieval, time into fixative, and a schematic of the location in the defect should be documented and transferred to the histologist. For some lesion sites, biopsies can only be collected oblique to the cartilage surface, and these may need to go deeper to collect subchondral bone (Figs. 2C and 2D). Also, despite best efforts by the surgeon to extract a biopsy from the middle of the repaired lesion, it is possible that the biopsy is retrieved outside the lesion. It is suggested that the blinded observers flag any biopsies with features suggestive of a nonrepresentative biopsy such as a well-formed tidemark or normal-appearing hyaline cartilage with a lamina splendens. In some repair samples, especially those slightly delaminated, the twisting motion used to extract the biopsy can lead to the bone or surface becoming separated from the cartilage repair in the biopsy specimen. Broken samples have previously been eliminated from some analyses61,68; however, the separate pieces can be processed together to obtain a subset of histological and histomorphometric values, which may reduce bias. Some features can still be scored even if the biopsy is not complete.

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.