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Acute Osteoclast Activity following Subchondral Drilling Is Promoted by Chitosan and Associated with Improved Cartilage Repair Tissue Integration.

Chen G, Sun J, Lascau-Coman V, Chevrier A, Marchand C, Hoemann CD - Cartilage (2011)

Bottom Line: Chitosan was retained at the top of the drill holes at 1 week as extracellular particles became internalized by granulation tissue cells at 2 weeks and was completely cleared by 8 weeks.Osteoclasts burst-accumulated at microdrill hole edges at 1 week, in new woven bone at the base of the drill holes at 2 weeks, and below endochondral cartilage repair at 8 weeks.Osteoclasts are cellular mediators of marrow-derived cartilage repair integration.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemical Engineering, Ecole Polytechnique, Montreal, Quebec, Canada.

ABSTRACT

Objective: Cartilage-bone integration is an important functional end point of cartilage repair therapy, but little is known about how to promote integration. We tested the hypothesis that chitosan-stabilized blood clot implant elicits osteoclasts to drilled cartilage defects and promotes repair and cartilage-bone integration.

Design: Bilateral trochlear defects in 15 skeletally mature rabbit knees were microdrilled and then treated with chitosan-glycerol phosphate (GP)/blood implant with fluorescent chitosan tracer and thrombin to accelerate in situ solidification or with thrombin alone. Chitosan clearance, osteoclast density, and osteochondral repair were evaluated at 1, 2, and 8 weeks at the outside, edge, and through the proximal microdrill holes.

Results: Chitosan was retained at the top of the drill holes at 1 week as extracellular particles became internalized by granulation tissue cells at 2 weeks and was completely cleared by 8 weeks. Osteoclasts burst-accumulated at microdrill hole edges at 1 week, in new woven bone at the base of the drill holes at 2 weeks, and below endochondral cartilage repair at 8 weeks. Implants elicited 2-fold more osteoclasts relative to controls (P < 0.001), a more complete drill hole bone repair, and improved cartilage-bone integration and histological tissue quality. Treated and control 8-week cartilage repair tissues contained 85% collagen type II. After 8 weeks of repair, subchondral osteoclast density correlated positively with bone-cartilage repair tissue integration (P < 0.0005).

Conclusions: Chitosan-GP/blood implant amplified the acute influx of subchondral osteoclasts through indirect mechanisms, leading to significantly improved repair and cartilage-bone integration without inducing net bone resorption. Osteoclasts are cellular mediators of marrow-derived cartilage repair integration.

No MeSH data available.


Related in: MedlinePlus

Treatment with thrombin-chitosan-GP/blood implant versus thrombin alone resulted in time-dependent alterations in subchondral osteoclast density (A), soft repair tissue formation (B), and repair integration (C) at 1, 2, and 8 weeks postoperatively and led to similar Safranin O–stained matrix at 8 weeks postoperatively (D), according to quantitative histomorphometry. Data show the average ± 95% confidence intervals. Levels 1, 2, and 3 refer to sections analyzed between, at the edge, and through the drill holes as indicated by the schematic. Significant differences specifically due to treatment (#) were analyzed at each time point using the general linear model (GLM), where all 3 levels were simultaneously analyzed with treatment as a predictor. *Significant effect due to treatment level 2 only (GLM with LSD post hoc). ^Nearly significant effect due to treatment for level 2 (paired Student t test). The arrow and circle arrow (C and F, right panels) show average values obtained from intact knee trochlea of immature (N = 4) and skeletally mature (N = 4) rabbit femurs, respectively.
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fig5-1947603510381096: Treatment with thrombin-chitosan-GP/blood implant versus thrombin alone resulted in time-dependent alterations in subchondral osteoclast density (A), soft repair tissue formation (B), and repair integration (C) at 1, 2, and 8 weeks postoperatively and led to similar Safranin O–stained matrix at 8 weeks postoperatively (D), according to quantitative histomorphometry. Data show the average ± 95% confidence intervals. Levels 1, 2, and 3 refer to sections analyzed between, at the edge, and through the drill holes as indicated by the schematic. Significant differences specifically due to treatment (#) were analyzed at each time point using the general linear model (GLM), where all 3 levels were simultaneously analyzed with treatment as a predictor. *Significant effect due to treatment level 2 only (GLM with LSD post hoc). ^Nearly significant effect due to treatment for level 2 (paired Student t test). The arrow and circle arrow (C and F, right panels) show average values obtained from intact knee trochlea of immature (N = 4) and skeletally mature (N = 4) rabbit femurs, respectively.

Mentions: The net effect of implant was to double the osteoclast density lining the drill holes at 1 week (P < 0.0001) (Fig. 5A). The chitosan implant also expanded the zone of acute osteoclast formation to subchondral areas between the drill holes at 1 week (Fig. 5A, level 1). After 2 weeks, osteoclast density increased below control defects, mainly along new woven bone forming at the base of all drill holes, and was slightly higher below treated defects (P = 0.023) (Fig. 5B, level 2). At 8 weeks, osteoclast density subsided, with more osteoclasts detected below treated than control defects (P = 0.023) (Fig. 5C). Osteoclast density in 8-week repair bone was similar to that of intact immature 4-month-old rabbit trochlea (Fig. 5C, horizontal arrow, 8 weeks). Osteoclasts were scarcely detected in sections from adult rabbits (Fig. 5C, horizontal circle arrow, 8 weeks).


Acute Osteoclast Activity following Subchondral Drilling Is Promoted by Chitosan and Associated with Improved Cartilage Repair Tissue Integration.

Chen G, Sun J, Lascau-Coman V, Chevrier A, Marchand C, Hoemann CD - Cartilage (2011)

Treatment with thrombin-chitosan-GP/blood implant versus thrombin alone resulted in time-dependent alterations in subchondral osteoclast density (A), soft repair tissue formation (B), and repair integration (C) at 1, 2, and 8 weeks postoperatively and led to similar Safranin O–stained matrix at 8 weeks postoperatively (D), according to quantitative histomorphometry. Data show the average ± 95% confidence intervals. Levels 1, 2, and 3 refer to sections analyzed between, at the edge, and through the drill holes as indicated by the schematic. Significant differences specifically due to treatment (#) were analyzed at each time point using the general linear model (GLM), where all 3 levels were simultaneously analyzed with treatment as a predictor. *Significant effect due to treatment level 2 only (GLM with LSD post hoc). ^Nearly significant effect due to treatment for level 2 (paired Student t test). The arrow and circle arrow (C and F, right panels) show average values obtained from intact knee trochlea of immature (N = 4) and skeletally mature (N = 4) rabbit femurs, respectively.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4300782&req=5

fig5-1947603510381096: Treatment with thrombin-chitosan-GP/blood implant versus thrombin alone resulted in time-dependent alterations in subchondral osteoclast density (A), soft repair tissue formation (B), and repair integration (C) at 1, 2, and 8 weeks postoperatively and led to similar Safranin O–stained matrix at 8 weeks postoperatively (D), according to quantitative histomorphometry. Data show the average ± 95% confidence intervals. Levels 1, 2, and 3 refer to sections analyzed between, at the edge, and through the drill holes as indicated by the schematic. Significant differences specifically due to treatment (#) were analyzed at each time point using the general linear model (GLM), where all 3 levels were simultaneously analyzed with treatment as a predictor. *Significant effect due to treatment level 2 only (GLM with LSD post hoc). ^Nearly significant effect due to treatment for level 2 (paired Student t test). The arrow and circle arrow (C and F, right panels) show average values obtained from intact knee trochlea of immature (N = 4) and skeletally mature (N = 4) rabbit femurs, respectively.
Mentions: The net effect of implant was to double the osteoclast density lining the drill holes at 1 week (P < 0.0001) (Fig. 5A). The chitosan implant also expanded the zone of acute osteoclast formation to subchondral areas between the drill holes at 1 week (Fig. 5A, level 1). After 2 weeks, osteoclast density increased below control defects, mainly along new woven bone forming at the base of all drill holes, and was slightly higher below treated defects (P = 0.023) (Fig. 5B, level 2). At 8 weeks, osteoclast density subsided, with more osteoclasts detected below treated than control defects (P = 0.023) (Fig. 5C). Osteoclast density in 8-week repair bone was similar to that of intact immature 4-month-old rabbit trochlea (Fig. 5C, horizontal arrow, 8 weeks). Osteoclasts were scarcely detected in sections from adult rabbits (Fig. 5C, horizontal circle arrow, 8 weeks).

Bottom Line: Chitosan was retained at the top of the drill holes at 1 week as extracellular particles became internalized by granulation tissue cells at 2 weeks and was completely cleared by 8 weeks.Osteoclasts burst-accumulated at microdrill hole edges at 1 week, in new woven bone at the base of the drill holes at 2 weeks, and below endochondral cartilage repair at 8 weeks.Osteoclasts are cellular mediators of marrow-derived cartilage repair integration.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemical Engineering, Ecole Polytechnique, Montreal, Quebec, Canada.

ABSTRACT

Objective: Cartilage-bone integration is an important functional end point of cartilage repair therapy, but little is known about how to promote integration. We tested the hypothesis that chitosan-stabilized blood clot implant elicits osteoclasts to drilled cartilage defects and promotes repair and cartilage-bone integration.

Design: Bilateral trochlear defects in 15 skeletally mature rabbit knees were microdrilled and then treated with chitosan-glycerol phosphate (GP)/blood implant with fluorescent chitosan tracer and thrombin to accelerate in situ solidification or with thrombin alone. Chitosan clearance, osteoclast density, and osteochondral repair were evaluated at 1, 2, and 8 weeks at the outside, edge, and through the proximal microdrill holes.

Results: Chitosan was retained at the top of the drill holes at 1 week as extracellular particles became internalized by granulation tissue cells at 2 weeks and was completely cleared by 8 weeks. Osteoclasts burst-accumulated at microdrill hole edges at 1 week, in new woven bone at the base of the drill holes at 2 weeks, and below endochondral cartilage repair at 8 weeks. Implants elicited 2-fold more osteoclasts relative to controls (P < 0.001), a more complete drill hole bone repair, and improved cartilage-bone integration and histological tissue quality. Treated and control 8-week cartilage repair tissues contained 85% collagen type II. After 8 weeks of repair, subchondral osteoclast density correlated positively with bone-cartilage repair tissue integration (P < 0.0005).

Conclusions: Chitosan-GP/blood implant amplified the acute influx of subchondral osteoclasts through indirect mechanisms, leading to significantly improved repair and cartilage-bone integration without inducing net bone resorption. Osteoclasts are cellular mediators of marrow-derived cartilage repair integration.

No MeSH data available.


Related in: MedlinePlus