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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

Quantitative measures of cartilage repair tissue collagen content and residual soft tissue area in microdrilled defects. (A) In 8-week repair tissues above the projected tidemark, collagen matrix composition through the drill holes was unchanged by treatment (N = 7, average ± standard deviation). (B-C) Soft tissue below the projected tidemark diminished over time in all drill holes; however, significantly more soft tissue remained below control defects at 8 weeks (D; N = 7, average ± 95% confidence intervals). Levels 1, 2, and 3 refer to sections analyzed between, at the edge, and through the drill holes. The horizontal arrow (B) refers to the theoretical initial area occupied by two 1.0-mm-diameter, 3.5-mm-deep microdrill holes.
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fig8-1947603510381096: Quantitative measures of cartilage repair tissue collagen content and residual soft tissue area in microdrilled defects. (A) In 8-week repair tissues above the projected tidemark, collagen matrix composition through the drill holes was unchanged by treatment (N = 7, average ± standard deviation). (B-C) Soft tissue below the projected tidemark diminished over time in all drill holes; however, significantly more soft tissue remained below control defects at 8 weeks (D; N = 7, average ± 95% confidence intervals). Levels 1, 2, and 3 refer to sections analyzed between, at the edge, and through the drill holes. The horizontal arrow (B) refers to the theoretical initial area occupied by two 1.0-mm-diameter, 3.5-mm-deep microdrill holes.

Mentions: Treated repair tissues over the drill holes had consistently more chondrocyte-like cells (O’Driscoll histological scores I and VII) (Table 2), higher structural integrity, healthier subchondral bone, and a higher total histological score (scores IV, X, and total) (Table 2). Significant histological differences due to treatment were only observed in sections through the drill holes in this relatively small sample group (N = 7). Most repair tissues were not bonded with adjacent cartilage, and all adjacent cartilage tissues showed some degree of degeneration. Collagen typing of the repair tissues at 8 weeks showed that treated and control repair matrix contained the same average area percentage of collagen type II (85%) and collagen type I (38%) (Fig. 8A). This result was partly due to a poor cartilage repair response in 2 of the 7 treated rabbits in the 8-week group that were skeletally aged to 24 months see (Fig. 7 O and P). Treated drill holes were slightly larger at 1 to 2 weeks than controls (Fig. 8 B and C) and more completely repaired with bone at 8 weeks compared to controls (Fig. 8D), which were frequently filled with collagen type II instead of collagen type I matrix (Fig. 7 C and D).


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)

Quantitative measures of cartilage repair tissue collagen content and residual soft tissue area in microdrilled defects. (A) In 8-week repair tissues above the projected tidemark, collagen matrix composition through the drill holes was unchanged by treatment (N = 7, average ± standard deviation). (B-C) Soft tissue below the projected tidemark diminished over time in all drill holes; however, significantly more soft tissue remained below control defects at 8 weeks (D; N = 7, average ± 95% confidence intervals). Levels 1, 2, and 3 refer to sections analyzed between, at the edge, and through the drill holes. The horizontal arrow (B) refers to the theoretical initial area occupied by two 1.0-mm-diameter, 3.5-mm-deep microdrill holes.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4300782&req=5

fig8-1947603510381096: Quantitative measures of cartilage repair tissue collagen content and residual soft tissue area in microdrilled defects. (A) In 8-week repair tissues above the projected tidemark, collagen matrix composition through the drill holes was unchanged by treatment (N = 7, average ± standard deviation). (B-C) Soft tissue below the projected tidemark diminished over time in all drill holes; however, significantly more soft tissue remained below control defects at 8 weeks (D; N = 7, average ± 95% confidence intervals). Levels 1, 2, and 3 refer to sections analyzed between, at the edge, and through the drill holes. The horizontal arrow (B) refers to the theoretical initial area occupied by two 1.0-mm-diameter, 3.5-mm-deep microdrill holes.
Mentions: Treated repair tissues over the drill holes had consistently more chondrocyte-like cells (O’Driscoll histological scores I and VII) (Table 2), higher structural integrity, healthier subchondral bone, and a higher total histological score (scores IV, X, and total) (Table 2). Significant histological differences due to treatment were only observed in sections through the drill holes in this relatively small sample group (N = 7). Most repair tissues were not bonded with adjacent cartilage, and all adjacent cartilage tissues showed some degree of degeneration. Collagen typing of the repair tissues at 8 weeks showed that treated and control repair matrix contained the same average area percentage of collagen type II (85%) and collagen type I (38%) (Fig. 8A). This result was partly due to a poor cartilage repair response in 2 of the 7 treated rabbits in the 8-week group that were skeletally aged to 24 months see (Fig. 7 O and P). Treated drill holes were slightly larger at 1 to 2 weeks than controls (Fig. 8 B and C) and more completely repaired with bone at 8 weeks compared to controls (Fig. 8D), which were frequently filled with collagen type II instead of collagen type I matrix (Fig. 7 C and D).

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