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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

Dynamic distribution of chitosan particles during articular cartilage regeneration in microdrilled cartilage defects, in unstained plastic sections. The red fluorescent signal shows RITC-chitosan, and the green (A) is autofluorescent bone. After 1 week of repair, chitosan particles resided at the top of drill holes (A) as an extracellular scaffold dispersed within the fibrin clot (B). Some chitosan adhered to the bone lining the drill hole side walls and the base of the defect (A, open arrows). At 2 weeks of repair, little or no extracellular chitosan remained (C), and most chitosan particles were internalized in vesicles of granulation tissue cells (D). The dotted arrows (in A and C) show the increased width of the treated drill hole at 2 weeks.
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fig2-1947603510381096: Dynamic distribution of chitosan particles during articular cartilage regeneration in microdrilled cartilage defects, in unstained plastic sections. The red fluorescent signal shows RITC-chitosan, and the green (A) is autofluorescent bone. After 1 week of repair, chitosan particles resided at the top of drill holes (A) as an extracellular scaffold dispersed within the fibrin clot (B). Some chitosan adhered to the bone lining the drill hole side walls and the base of the defect (A, open arrows). At 2 weeks of repair, little or no extracellular chitosan remained (C), and most chitosan particles were internalized in vesicles of granulation tissue cells (D). The dotted arrows (in A and C) show the increased width of the treated drill hole at 2 weeks.

Mentions: In histological sections, fluorescent chitosan particles were limited to the top of the drill holes (Fig. 2 A and C). Particles became transformed from an extracellular scaffold at 1 week to intracellular vesicles in granulation tissue cells at 2 weeks (Fig. 1 G-I and Fig. 2 B and D). Occasional fluorescent implant fragments were seen in the fat pad or synovium lining the trochlear ridge (data not shown). At 1 week, some chitosan coated the bone surfaces at the top of the drill hole and along the base of the defect (Fig. 2A, open arrows). To summarize, these data showed that chitosan particles resided at the top of all treated drill holes and were actively cleared over several weeks by granulation tissue cells.


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)

Dynamic distribution of chitosan particles during articular cartilage regeneration in microdrilled cartilage defects, in unstained plastic sections. The red fluorescent signal shows RITC-chitosan, and the green (A) is autofluorescent bone. After 1 week of repair, chitosan particles resided at the top of drill holes (A) as an extracellular scaffold dispersed within the fibrin clot (B). Some chitosan adhered to the bone lining the drill hole side walls and the base of the defect (A, open arrows). At 2 weeks of repair, little or no extracellular chitosan remained (C), and most chitosan particles were internalized in vesicles of granulation tissue cells (D). The dotted arrows (in A and C) show the increased width of the treated drill hole at 2 weeks.
© Copyright Policy
Related In: Results  -  Collection

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

fig2-1947603510381096: Dynamic distribution of chitosan particles during articular cartilage regeneration in microdrilled cartilage defects, in unstained plastic sections. The red fluorescent signal shows RITC-chitosan, and the green (A) is autofluorescent bone. After 1 week of repair, chitosan particles resided at the top of drill holes (A) as an extracellular scaffold dispersed within the fibrin clot (B). Some chitosan adhered to the bone lining the drill hole side walls and the base of the defect (A, open arrows). At 2 weeks of repair, little or no extracellular chitosan remained (C), and most chitosan particles were internalized in vesicles of granulation tissue cells (D). The dotted arrows (in A and C) show the increased width of the treated drill hole at 2 weeks.
Mentions: In histological sections, fluorescent chitosan particles were limited to the top of the drill holes (Fig. 2 A and C). Particles became transformed from an extracellular scaffold at 1 week to intracellular vesicles in granulation tissue cells at 2 weeks (Fig. 1 G-I and Fig. 2 B and D). Occasional fluorescent implant fragments were seen in the fat pad or synovium lining the trochlear ridge (data not shown). At 1 week, some chitosan coated the bone surfaces at the top of the drill hole and along the base of the defect (Fig. 2A, open arrows). To summarize, these data showed that chitosan particles resided at the top of all treated drill holes and were actively cleared over several weeks by granulation tissue cells.

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