纳米羟基磷灰石／壳聚糖复合支架修复兔股骨髁临界性骨缺损的实验研究

Repair of critical-sized bone defects of the femoral condyle with nano-hydroxyapatite/chitosan corn-posites in rabbits

目的探讨纳米羟基磷灰石（nHA）／壳聚糖（CS）复合支架修复兔股骨髁临界性骨缺损的能力。方法取44只健康成年新西兰大白兔，于兔左侧股骨外侧髁建立临界性骨缺损（直径为6mm、深为10him）模型，随机分为3组：实验组（n=20）：骨缺损处植入nHA／CS复合材料；对照组（n=20）：骨缺损处植入单纯CS；空白组（n=4）：骨缺损处旷置，不植入任何材料。术后8、12周取材行大体观察、X线摄片、显微CT扫描及组织学观察，比较各组骨缺损的修复能力。结果术后12周X线片显示实验组骨缺损修复良好，骨皮质连续；对照组缺损区明显缩小，两断端不连接；空白组缺损区无明娃骨痂生成。实验组和对照组Lane-SandhuX射线评分平均分别为（10．18±0．98）、（8．90±0．99）分，两组比较差异有统计学意义（t=6．858，P=0．000）。显微CT扫描显示：实验组骨缺损基本完全修复，股骨髁外形恢复正常；对照组骨缺损空腔大部分为新生骨组织填充，缺损区仍留有缺损；空白组骨缺损綦本无修复。实验组和对照组CT值平均分别为（256．1±26．8）、（169．2±25．4）Hu，两组比较差异有统计学意义（t=4．711，P=0．003）。术后12周组织学观察显示：实验组可见大量新生骨小梁，新生骨质与周围骨床之间无明显分界线；对照组可见骨缺损为剩余材料与纤维组织充填；空白组骨缺损区均被少量纤维组织充填。结论nHA／CS复合材料较单纯CS能更好地促进兔股骨髁临界性骨缺损的修复，是一种很有应用前景的组织工程修复材料。

Objective To investigate the bone regeneration potential of nano-hydroxyapatite/chi- tosan composite scaffolds when implanted into critical-sized bone defects in rabbit femoral condyles. Methods Critical-sized bone defects （6 mm in diameter and 10 mm in depth） were created in the left femoral condyles of 44 adult New Zealand white rabbits. All the rabbits were randomly divided into 3 groups according to bone grafts. Nano-hydroxyapatite/chitosan compositions were implanted into the defects in the experimental group （ n = 20）, pure chitosan in the control group （ n = 20）, and nothing in the blank group （n =4） . New bone formation was detected and compared among the 3 groups by gross observation, plain radiography, quantitative computer tomography （CT） and histological examination at 8 and 12 weeks after surgery. Results Plain radiography at 12 weeks after surgery showed that bone defects were being re- paired well and cortic.al bone union was observed in the experimental group, and that the depth of defect di- minished but bony connection was not achieved in the control group, and that there was no new bone formation in the blank group. The Lane-Sandhu X-ray scores were 10. 18 ± 0.98 in the experimental group and 8.90 ± 0.99 in the control group, with a significant difference between the 2 groups （ t =6. 858, P =0. 000）. At 12 weeks, CT showed that the defects were almost filled with new osteoid tissue and the bone contour remodeled smoothly in the experimental group; most of the defects were filled with new osteoid tissue but still visible in the control group; bony union was not achieved and the defects were still very obvious in the blank group. The CT scores were 256. 1 ± 26. 8 Hu in the experimental group and 169.2 ± 25.4 Hu in the control group, with a significant difference （ t = 4. 711, P = 0. 003）. The histological observation showed a lot of trabecular bone in the bone defects at 12 weeks in the experimental group, with no visible boundary between newly formed bone tissue and native bone. In the control group, the bone defects were full of the remnant material and fibrous tissue at 12 weeks. In the blank group, the bone defects were filled with a little fibrous tissue at 12 weeks but no new bone formed. Conclusion Since nano-hydroxyapatite/chitosan composite scaffolds may have better performance than pure chitosan in repair of bone defects, it is a sort of promising candidate material for regeneration of bone loss.