中国组织工程研究 ›› 2025, Vol. 29 ›› Issue (30): 6426-6433.doi: 10.12307/2025.919

• 组织构建实验造模 experimental modeling in tissue construction • 上一篇    下一篇

骨质疏松性股骨髁骨缺损兔模型制备及其临界值

邓光慧1,向  炜2,苏其帆2,陈小鱼2,王亮为2,万志宏2,吴佳奇2,陈孝均2   

  1. 1西南医科大学附属医院骨科,四川省泸州市  646000;2西南医科大学附属中医医院骨科,四川省泸州市  646000


  • 收稿日期:2024-09-25 接受日期:2024-11-22 出版日期:2025-10-28 发布日期:2025-03-27
  • 通讯作者: 陈孝均,博士,副主任医师,西南医科大学附属中医医院骨科,四川省泸州市 646000
  • 作者简介:邓光慧,女,1999年生,四川省自贡市人,汉族,2025年西南医科大学毕业,硕士,医师,主要从事骨与关节疾病的研究。
  • 基金资助:
    泸州市人民政府-西南科大学科技战略合作项目(2019LZXNYDJ37),项目负责人:陈孝均

Preparation of osteoporotic femoral condylar bone defect model in rabbits and its critical value

Deng Guanghui1, Xiang Wei2, Su Qifan2, Chen Xiaoyu2, Wang Liangwei2, Wan Zhihong2, Wu Jiaqi2, Chen Xiaojun2   

  1. 1Department of Orthopedics, The Affiliated Hospital, Southwest Medical University, Luzhou 646000, Sichuan Province, China; 2Department of Orthopedics, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou 646000, Sichuan Province, China
  • Received:2024-09-25 Accepted:2024-11-22 Online:2025-10-28 Published:2025-03-27
  • Contact: Chen Xiaojun, MD, Associate chief physician, Department of Orthopedics, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou 646000, Sichuan Province, China
  • About author:Deng Guanghui, MS, Physician, Department of Orthopedics, The Affiliated Hospital, Southwest Medical University, Luzhou 646000, Sichuan Province, China
  • Supported by:
    Luzhou Municipal People’s Government-Southwest Medical University of Science and Technology Strategic Cooperation Project, No. 2019LZXNYDJ37 (to CXJ)

摘要:


文题释义:
临界骨缺损(critical size bone defect,CSD):指在特定骨和动物物种中,活体动物不会自发愈合的最小骨缺损,其大小并不是唯一参数。大多数物种的骨缺损长度超过骨直径的1.5倍或2倍时可以考虑为最小尺寸。
骨小梁间隙:指骨小梁之间的空隙大小。骨小梁的间隙越大,可能会对骨骼的承载力造成影响。

背景:大多数物种的骨缺损长度超过骨直径的1.5或2倍时可以考虑为临界骨缺损,当骨缺损体积达到临界值时便不能自身愈合。目前,对于兔骨质疏松性股骨髁临界骨缺损的大小,尚无统一的标准。
目的:建立兔骨质疏松性股骨髁不同尺寸骨缺损模型,确定兔骨质疏松性股骨髁临界骨缺损的大小。
方法:将36只3月龄雌性新西兰大白兔随机分为卵巢切除组(n=30)和假手术组(n=6)。卵巢切除组兔行双侧卵巢切除建立骨质疏松模型,再进一步建立不同直径(直径分别为4,5,6,7 mm,深度为8 mm)股骨髁骨缺损的模型;假手术组兔不切除卵巢。于建模后第8,12周,每组随机抽取3只行CT扫描及三维重建,评价骨缺损愈合情况;之后取材进行大体观察和苏木精-伊红染色观察股骨髁骨缺损区域新生骨生长情况。
结果与结论:①骨质疏松建模和股骨髁骨缺损建模术后所有兔均存活,活动良好;②骨质疏松建模术后第12周,双能X射线吸收法检测结果提示卵巢切除组兔腰椎骨密度值较假手术组显著降低(P < 0.05);苏木精-伊红染色显示卵巢切除组骨小梁变细、变稀疏;骨组织面积占比卵巢切除组显著低于假手术组(P=0.00);Micro-CT结果提示卵巢切除组兔股骨髁骨组织参数与假手术组比较差异有显著性意义(P < 0.05),卵巢切除组表现出明显的骨质疏松特征;③术后第12周CT显示,直径4 mm和5 mm组骨缺损基本完全修复;直径6 mm组新生骨组织较多,但骨缺损中心部位尚未完全修复;直径7 mm组少量新生骨组织长入,骨缺损明显;④术后第12周大体观察,直径4 mm和5 mm组股骨髁骨缺损被完全修复;直径6 mm和7 mm 组骨缺损区可见明显凹陷,骨缺损未被完全修复;⑤术后12周组织学观察,直径4 mm和5 mm组骨缺损区完全由新生骨填充,骨小梁结构不规则;而直径6 mm和7 mm组周边有新生骨小梁,中心区域骨缺损依然明显;⑥结果说明,在兔骨质疏松性股骨髁骨缺损12周的实验观察期内,在缺损深度同为8 mm的条件下,直径≥6 mm的股骨髁骨缺损不能自行愈合,而直径< 6 mm的股骨髁骨缺损被完全修复;直径6 mm、深度8 mm可作为兔骨质疏松性股骨髁临界骨缺损值。  
https://orcid.org/0009-0006-7327-061X(邓光慧)

中国组织工程研究杂志出版内容重点:组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程

关键词: 临界骨缺损, 骨质疏松, 股骨髁, 模型, 兔, Micro-CT, DXA, 骨组织工程

Abstract: BACKGROUND: In most species, a bone defect that is longer than 1.5 or 2 times its diameter can be considered a critical bone defect, and when the bone defect volume reaches the critical value, it cannot heal on its own. Currently, there is no uniform standard for the size of critical-sized defects in the osteoporotic femoral condyle of rabbits.
OBJECTIVE: To establish a rabbit model with different sizes of bone defects in the osteoporotic femoral condyle and to determine the critical-sized defects of osteoporotic femoral condyle in rabbits.
METHODS: Thirty-six 3-month-old female New Zealand white rabbits were randomly divided into ovariectomy group (n=30) and sham operation group (n=6). Rabbits in the ovariectomy group underwent bilateral ovariectomy to establish an osteoporosis model, and then femoral condyle bone defect models of different diameters (diameters were 4, 5, 6, and 7 mm, and depths were 8 mm) were further established; rabbits in the sham operation group did not undergo ovariectomy. At 8 and 12 weeks after modeling, 3 rats were randomly selected from each group for CT scanning and three-dimensional reconstruction to evaluate the healing of bone defects. Afterwards, samples were taken for gross observation and hematoxylin-eosin staining to observe the growth of new bone in the femoral condyle bone defect area.
RESULTS AND CONCLUSION: (1) All rabbits survived and moved well after modeling of osteoporosis and femoral condyle bone defect. (2) At 12 weeks after osteoporosis modeling, dual-energy X-ray absorptiometry results showed that the bone mineral density of lumbar vertebrae in ovariectomy group was significantly lower than that in sham operation group (P < 0.05). Hematoxylin-eosin staining showed that the bone trabeculae in the ovariectomy group became thinner and sparse. The proportion of bone tissue area in the ovariectomy group was significantly lower than that in the sham operation group (P=0.00). Micro-CT results showed that the bone tissue parameters of the femoral condyle in the ovariectomy group were significantly different from those in the sham operation group (P < 0.05), and the ovariectomy group showed obvious characteristics of osteoporosis. (3) CT showed that the bone defect in the 4 mm and 5 mm diameter groups was basically completely repaired at 12 weeks after surgery. There was more new bone tissue in the 6 mm diameter group, but the central part of the bone defect was not completely repaired. A small amount of new bone tissue grew in the 7 mm diameter group, and the bone defect was obvious. (4) Gross observation at 12 weeks after surgery showed that the femoral condyle bone defect in the 4 mm and 5 mm diameter groups was completely repaired. Obvious depression was seen in the bone defect area of the 6 mm and 7 mm diameter groups, and the bone defect was not completely repaired. (5) Histological observation at 12 weeks after surgery showed that the bone defect area of the 4 mm and 5 mm diameter groups was completely filled with new bone, and the trabecular structure was irregular; while there were new trabeculae in the periphery of the 6 mm and 7 mm diameter groups, and the bone defect in the central area was still obvious. (6) The results showed that during the 12-week experimental observation period of osteoporotic femoral condyle defects in rabbits, under the condition of the same defect depth of 8 mm, femoral condyle defects with a diameter ≥ 6 mm could not heal on their own, while femoral condyle defects with a diameter < 6 mm were completely repaired. A diameter of 6 mm and a depth of 8 mm can be used as the critical bone defect value of osteoporotic femoral condyle in rabbits.

中国组织工程研究杂志出版内容重点:组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程

Key words: critical bone defect, osteoporosis, femoral condyle, model, rabbit, Micro-CT, DXA, bone tissue engineering

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