Department of Chemical Engineering, École Polytechnique, Montréal, QC, Canada.
Osteoarthritis Cartilage. 2013 Jun;21(6):849-59. doi: 10.1016/j.joca.2013.03.012. Epub 2013 Mar 21.
Cartilage repair elicited by bone marrow stimulation can be enhanced by a chitosan-glycerol phosphate (GP)/blood implant, through mechanisms involving therapeutic inflammatory angiogenesis. The implant is formed by in situ coagulation, which can be accelerated by adding coagulation factors. We hypothesized that coagulation factors enhance acute subchondral angiogenesis in repairing drilled defects.
Full-thickness cartilage defects were created bilaterally in 12 skeletally mature rabbit knee trochlea, microdrilled, then allowed to bleed as a control (N = 6) or treated with chitosan-GP/blood implant (N = 6), or implant solidified with thrombin (IIa), tissue factor (TF) with recombinant human factor VIIa (rhFVIIa), or rhFVIIa alone (N = 4 each condition). At 3 weeks post-operative, quantitative stereology was used to obtain blood vessel length (L(V)), surface (S(V)), and volume (V(V)) density at systematic depths in two microdrill holes per defect. Collagen type I, type II and glycosaminoglycan (GAG) percent stain in non-mineralized repair tissue were analysed by histomorphometry.
All drill holes were healing, and showed a depth-dependent increase in granulation tissue blood vessel density (Lv, Sv, and Vv, P < 0.005). Residual chitosan implant locally suppressed blood vessel ingrowth into the granulation tissue, whereas holes completely cleared of chitosan amplified angiogenesis vs microdrill-only (P = 0.049), an effect enhanced by IIa. Chitosan implant suppressed strong Col-I, Col-II, and GAG accumulation that occurred spontaneously in drill-only bone defects (P < 0.005) and coagulation factors did not alter this effect.
Subchondral angiogenesis is promoted by chitosan implant clearance. Chitosan implant treatment suppresses fibrocartilage scar tissue formation, and promotes bone remodeling, which allows more blood vessel migration and woven bone repair towards the cartilage lesion area.
通过诱导骨髓刺激的软骨修复，可以通过涉及治疗性炎症血管生成的机制，增强壳聚糖-甘油磷酸（GP）/血液植入物的效果。该植入物通过原位凝固形成，通过添加凝血因子可以加速凝固。我们假设凝血因子增强了修复钻孔缺陷时的急性软骨下血管生成。
在 12 只骨骼成熟的兔膝关节滑车双侧创建全层软骨缺损，微钻孔，然后让其出血作为对照（N = 6）或用壳聚糖-GP/血液植入物（N = 6）治疗，或用凝血酶（IIa）、组织因子（TF）和重组人凝血因子 VIIa（rhFVIIa）凝固植入物，或单独用 rhFVIIa 凝固植入物（N = 4 每种情况）。术后 3 周，使用定量立体学方法获得每个缺陷的两个微钻孔中系统深度的血管长度（L(V)）、表面（S(V)）和体积（V(V)）密度。通过组织形态计量学分析非矿化修复组织中 I 型胶原、II 型胶原和糖胺聚糖（GAG）的百分比染色。
所有钻孔都在愈合，并且在肉芽组织血管密度（Lv、Sv 和 Vv，P < 0.005）方面表现出深度依赖性增加。残留的壳聚糖植入物局部抑制肉芽组织内血管生成，而完全清除壳聚糖的孔则增强了与微钻孔单独钻孔相比的血管生成（P = 0.049），这一效应被 IIa 增强。壳聚糖植入物抑制了在仅钻孔的骨缺损中自发发生的强烈的 Col-I、Col-II 和 GAG 积累（P < 0.005），并且凝血因子没有改变这种效应。
软骨下血管生成是由壳聚糖植入物清除促进的。壳聚糖植入物治疗抑制纤维软骨瘢痕组织形成，并促进骨重塑，这允许更多的血管迁移和编织骨修复向软骨病变区域。
