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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

Residency and clearance of chitosan particles in microdrilled cartilage defects. Full-thickness cartilage defects were microdrilled (A) and loaded with fluorescent chitosan-GP/blood implant that solidified in situ (B). Fluorescent chitosan particles were retained over all 4 microdrill holes after 1 week in vivo (C and D), showed diminished fluorescent signal at 2 weeks (E), and were no longer detectable at 8 weeks (F). Implants solidified in situ with thrombin (D) retained more chitosan than implants solidified without thrombin (C) (representative data from N = 2). Extracellular chitosan at 1 week (G) was internalized by repair cells at 2 weeks (H and I, white arrows). Scale bars in panels C to F are 1 mm.
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fig1-1947603510381096: Residency and clearance of chitosan particles in microdrilled cartilage defects. Full-thickness cartilage defects were microdrilled (A) and loaded with fluorescent chitosan-GP/blood implant that solidified in situ (B). Fluorescent chitosan particles were retained over all 4 microdrill holes after 1 week in vivo (C and D), showed diminished fluorescent signal at 2 weeks (E), and were no longer detectable at 8 weeks (F). Implants solidified in situ with thrombin (D) retained more chitosan than implants solidified without thrombin (C) (representative data from N = 2). Extracellular chitosan at 1 week (G) was internalized by repair cells at 2 weeks (H and I, white arrows). Scale bars in panels C to F are 1 mm.

Mentions: Implant residency was analyzed in rabbits that were immediately mobile following surgery and had unrestrained activity for the entire repair period. Fluorescent chitosan implant was macroscopically retained over all microdrill holes at 1 week postoperatively, with diminished intensity after 2 weeks, and was completely cleared after 8 weeks of repair (Fig. 1). These data were consistent with a previous report that fast green–stained chitosan particles were cleared by 5 weeks of repair in a similar cartilage repair model using implants without thrombin.24 To verify the influence of thrombin on implant retention, 2 rabbits in this study received implant without and with thrombin to accelerate in situ solidification.30 More RITC-chitosan was retained in defects pretreated with thrombin (Fig. 1 C and D). All other defects received either thrombin implant (treated) or thrombin only (control). Since thrombin was a controlled variable, repair reactions in treated defects could be attributed to the chitosan clot implant.


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)

Residency and clearance of chitosan particles in microdrilled cartilage defects. Full-thickness cartilage defects were microdrilled (A) and loaded with fluorescent chitosan-GP/blood implant that solidified in situ (B). Fluorescent chitosan particles were retained over all 4 microdrill holes after 1 week in vivo (C and D), showed diminished fluorescent signal at 2 weeks (E), and were no longer detectable at 8 weeks (F). Implants solidified in situ with thrombin (D) retained more chitosan than implants solidified without thrombin (C) (representative data from N = 2). Extracellular chitosan at 1 week (G) was internalized by repair cells at 2 weeks (H and I, white arrows). Scale bars in panels C to F are 1 mm.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4300782&req=5

fig1-1947603510381096: Residency and clearance of chitosan particles in microdrilled cartilage defects. Full-thickness cartilage defects were microdrilled (A) and loaded with fluorescent chitosan-GP/blood implant that solidified in situ (B). Fluorescent chitosan particles were retained over all 4 microdrill holes after 1 week in vivo (C and D), showed diminished fluorescent signal at 2 weeks (E), and were no longer detectable at 8 weeks (F). Implants solidified in situ with thrombin (D) retained more chitosan than implants solidified without thrombin (C) (representative data from N = 2). Extracellular chitosan at 1 week (G) was internalized by repair cells at 2 weeks (H and I, white arrows). Scale bars in panels C to F are 1 mm.
Mentions: Implant residency was analyzed in rabbits that were immediately mobile following surgery and had unrestrained activity for the entire repair period. Fluorescent chitosan implant was macroscopically retained over all microdrill holes at 1 week postoperatively, with diminished intensity after 2 weeks, and was completely cleared after 8 weeks of repair (Fig. 1). These data were consistent with a previous report that fast green–stained chitosan particles were cleared by 5 weeks of repair in a similar cartilage repair model using implants without thrombin.24 To verify the influence of thrombin on implant retention, 2 rabbits in this study received implant without and with thrombin to accelerate in situ solidification.30 More RITC-chitosan was retained in defects pretreated with thrombin (Fig. 1 C and D). All other defects received either thrombin implant (treated) or thrombin only (control). Since thrombin was a controlled variable, repair reactions in treated defects could be attributed to the chitosan clot implant.

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