Ⅰ型胶原-血管内皮生长因子缓释材料促进兔骨-肌腱结合部位愈合的作用

Role of sustained release type Ⅰ collagen-vascular endothelial growth factor in promoting bonetendon junction defect healing in rabbits

目的观察Ⅰ型胶原-血管内皮生长因子（VEGF）缓释材料对骨-肌腱结合部位损伤愈合的促进作用。方法建立兔部分髌骨切除模型，将制备的Ⅰ型胶原-VEGF缓释支架材料植入髌骨-髌腱结合部位。72只新西兰大白兔按随机数字表法分为对照组、Ⅰ型胶原组和Ⅰ型胶原-VEGF组，每组24只。术后4，8，12周取材，X线片及组织学检测观察髌骨-髌腱结合部位愈合情况，生物力学检测其愈合质量。结果X线片显示，术后4，8，12周对照组新生骨面积分别为（2．1±0．6）mm^2、（4．1±0．3）mm^2、（6．6±0．6）mm^2，Ⅰ型胶原组分别为（4．1±0．4）mm^2、（12．1±0．5）mm^2、（13．0±1．2）mm^2，Ⅰ型胶原-VEGF组分别为（3．8±0．4）mm^2、（11．0±0．5）mm^2、（13．1±1．0）mm^2，与对照组比较，Ⅰ型胶原组和Ⅰ型胶原-VEGF组各时相点新生骨面积均明显增多（P〈0．05）。组织学检测显示，对照组新生骨少，有大量纤维细胞聚集，肌腱纤维排列紊乱；Ⅰ型胶原-VEGF组大量新骨形成，胶原纤维组织排列整齐有序，术后4，8周有大量糖胺多糖表达，以纤维软骨修复为主；Ⅰ型胶原组有大量新骨形成，但肌腱端胶原纤维修复差，术后糖胺多糖表达量少，以纤维修复为主。生物力学结果显示，Ⅰ型胶原组、Ⅰ型胶原-VEGF组及对照组的极限拉应力均随时间的推移而增大，12周极限拉应力均明显大于4，8周；相同时相点极限拉应力比较，Ⅰ型胶原-VEGF组〉I型胶原组〉对照组（P〈0．05）。结论Ⅰ型胶原-VEGF缓释材料能早期提高骨-肌腱结合部位生物力学性能，促进愈合及纤维软骨带的形成。

Objective To observe the effect of sustained release type Ⅰ collagen-vascular endothelial growth factor （ VEGF ） on healing of bone-tendon junction injuries. Methods Partial patellectomy was conducted in 72 rabbits divided equally into control group, type Ⅰ collagen group, and collagen type Ⅰ-VEGF group. The scaffold was planted into the bone-tendon interface. Animals were sacrificed at 4, 8 and 12 weeks. New bone formation into the patella-patella tendon surface was detected using X-ray films and histological observations. Quality of bone healing was assayed using biomechanieal testing. Results At postoperative 4, 8 and 12 weeks, X-ray films showed bone formation of type I collagen group [ （4. 1 ± 0. 4 ） mm^2, （ 12.1 ± 0.5 ） mm^2, （ 13.0 ± 1.2 ） mm^2 respectively ] and of collagen type Ⅰ-VEGF group [ （ 3.8 ±0. 4） mm^2, （ 11.0 ± 0.5 ） mm^2, （ 13.1 ± 1.0 ） mm^2 respectively ] were more than that of control group [ （ 2. 1±0. 6 ） mm^2, （ 4.1 ± 0.3 ） mm^2, （ 6.6 ± 0.6 ） mm^2 respectively ] （ P 〈 0. 05 ）. Histology identified few new bone, massive fibrocyte accumulation and disrupted alignment of tendon fiber in control group, massive new bone formation, neat and orderly alignment of collagen fiber tissues and massive aggrecan expression at postoperative 4 and 8 weeks （fibrous cartage repair in largely） in collagen type Ⅰ-VEGF group, and massive new bone formation but worse alignment of tendon collagen fibers and less aggrecan expression （fibrous repair in largely） in type Ⅰ collagen group. Biomechanical test showed the ultimate tensile strength increased over time in all groups, with significantly higher value at 12 weeks than that at 4 and 8 weeks. At the same time point, ultimate tensile strength ranged in an order as follows ： collagen type Ⅰ-VEGF group 〉 collagen type Ⅰ group 〉 control group （ P 〈 0. 05 ）. Conclusion Sustained release type Ⅰ collagen-VEGF can accelerate early healing of bone-tendon junction injury and improve the histological and mechanical properties.