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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

An example of integration of repair tissues at 2 weeks (top panels, nondecalcified plastic sections) and 8 weeks (bottom panels, decalcified cryosections) in control (A and B) and treated (C and D) defects. The black arrows in A1, B1, C1, and D1 indicate the region shown in the adjacent panel.
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fig6-1947603510381096: An example of integration of repair tissues at 2 weeks (top panels, nondecalcified plastic sections) and 8 weeks (bottom panels, decalcified cryosections) in control (A and B) and treated (C and D) defects. The black arrows in A1, B1, C1, and D1 indicate the region shown in the adjacent panel.

Mentions: In 2-week control repair tissues, we observed that marrow-derived tissue tended to form more cohesive bonds within the newly formed repair matrix rather than attaching to the bone (Fig. 6A2). This morphology was frequently followed at 8 weeks by repair tissue “sprouting” from the drill holes without attaching to the bone base of the defect (Fig. 6B). Treated repair tissues formed cell-bone matrix attachments at 2 weeks (Fig. 6C), which was followed by integrated repair at 8 weeks (Fig. 6D). In quantifying the percentage of repair tissue detached from the bone base of the defects, we noted that fibrin clot and granulation repair tissues were quite fragile and could tear during cryosectioning; however, detached repair tissues observed at 8 weeks showed smooth repair tissue surfaces facing the bone, suggesting the tissue was detached in vivo and not a sectioning artefact (Fig. 6B2). After 1 to 2 weeks of repair, all defects showed a similar level of tissue detachment (Fig. 5 G and H), but after 8 weeks of repair, control defects showed significantly more detached cartilage repair throughout the proximal defect (P < 0.001) (Fig. 5I), especially at the edge of the drill hole (Fig. 5I, level 2, 8 weeks). Control tissues tended to be depleted of glycosaminoglycan at the edge of the hole (P = 0.066) (Fig. 5J, level 2).


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)

An example of integration of repair tissues at 2 weeks (top panels, nondecalcified plastic sections) and 8 weeks (bottom panels, decalcified cryosections) in control (A and B) and treated (C and D) defects. The black arrows in A1, B1, C1, and D1 indicate the region shown in the adjacent panel.
© Copyright Policy
Related In: Results  -  Collection

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

fig6-1947603510381096: An example of integration of repair tissues at 2 weeks (top panels, nondecalcified plastic sections) and 8 weeks (bottom panels, decalcified cryosections) in control (A and B) and treated (C and D) defects. The black arrows in A1, B1, C1, and D1 indicate the region shown in the adjacent panel.
Mentions: In 2-week control repair tissues, we observed that marrow-derived tissue tended to form more cohesive bonds within the newly formed repair matrix rather than attaching to the bone (Fig. 6A2). This morphology was frequently followed at 8 weeks by repair tissue “sprouting” from the drill holes without attaching to the bone base of the defect (Fig. 6B). Treated repair tissues formed cell-bone matrix attachments at 2 weeks (Fig. 6C), which was followed by integrated repair at 8 weeks (Fig. 6D). In quantifying the percentage of repair tissue detached from the bone base of the defects, we noted that fibrin clot and granulation repair tissues were quite fragile and could tear during cryosectioning; however, detached repair tissues observed at 8 weeks showed smooth repair tissue surfaces facing the bone, suggesting the tissue was detached in vivo and not a sectioning artefact (Fig. 6B2). After 1 to 2 weeks of repair, all defects showed a similar level of tissue detachment (Fig. 5 G and H), but after 8 weeks of repair, control defects showed significantly more detached cartilage repair throughout the proximal defect (P < 0.001) (Fig. 5I), especially at the edge of the drill hole (Fig. 5I, level 2, 8 weeks). Control tissues tended to be depleted of glycosaminoglycan at the edge of the hole (P = 0.066) (Fig. 5J, level 2).

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