中国组织工程研究

中国组织工程研究 ›› 2017, Vol. 21 ›› Issue (34): 5526-5531.doi: 10.3969/j.issn.2095-4344.2017.34.019

• 材料生物相容性 material biocompatibility • 上一篇    下一篇

骨形态发生蛋白2/Ⅰ型胶原凝胶修复前交叉韧带损伤

王  智1，杨大志2，欧阳建安2，王庆贺1
  

  1. 1深圳市南山区西丽人民医院骨科，广东省深圳市  518052；2广东医科大学附属南山医院骨科，广东省深圳市  518052
  • 收稿日期:2017-09-03 出版日期:2017-12-08 发布日期:2018-01-04
  • 通讯作者: 杨大志，硕士生导师，副主任医师，广东医科大学附属南山医院骨科，广东省深圳市 518052
  • 作者简介:王智，男，1965年生，安徽省淮南市人，汉族，副主任医师，主要从事膝关节重建修复研究。
  • 基金资助:

    2015年广东省自然科学基金项目(2015A030313877)；2015年深圳市科技创新委员会基础研究项目(JCYJ20150402095641635)

Bone morphogenetic protein-2/type I collagen hydrogels for anterior cruciate ligament injury

Wang Zhi1, Yang Da-zhi2, Ouyang Jian-an2, Wang Qing-he1
  

  1. 1Department of Orthopedics, Xili Hospital, Shenzhen 518052, Guangdong Province, China; 2Department of Orthopedics, Nanshan Hospital, Guangdong Medical University, Shenzhen 518052, Guangdong Province, China
  • Received:2017-09-03 Online:2017-12-08 Published:2018-01-04
  • Contact: Yang Da-zhi, Master’s supervisor, Associate chief physician, Department of Orthopedics, Nanshan Hospital, Guangdong Medical University, Shenzhen 518052, Guangdong Province, China
  • About author:Wang Zhi, Associate chief physician, Department of Orthopedics, Xili Hospital, Shenzhen 518052, Guangdong Province, China
  • Supported by:
    the Natural Science Foundation of Guangdong Province in 2015, No. 2015A030313877; the Basic Research Project of Shenzhen Science and Technology Innovation Committee in 2015, No. JCYJ20150402095641635

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摘要：

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文题释义：
骨形态发生蛋白：是美国Urist教授1963年发现的，能够诱导动物或人体间充质细胞分化为骨、软骨、韧带、肌腱和神经组织，是与胚胎骨骼形成有关的蛋白质，在骨形成的数个阶段均起作用，由形态发生的早期阶段开始，并延续至出生后，在中枢神经的发生中也起着关键作用。
腱-骨愈合：首先形成富含血管的纤维结缔组织带(界面组织)填充在腱与骨之间，随后来源于隧道骨组织的成纤维细胞逐渐长入，形成连接，继而形成类似直接止点的结构。肌腱骨止点在愈合过程中的形态学特征有显著变化，肌腱和骨的愈合先是骨长入二者之间，形成成纤维血管界面组织，界面组织逐步矿化，骨长入肌腱，重新建立肌腱骨界面连续的胶原纤维结构。
 
背景：在前交叉韧带重建过程中，骨形态发生蛋白2/Ⅰ型胶原凝胶对腱-骨愈合的影响尚无定论。
目的：观察兔前交叉韧带重建过程中，骨形态发生蛋白2/Ⅰ型胶原凝胶对前交叉韧带损伤腱-骨愈合的修复作用。
方法：取18只新西兰大白兔，制作右膝前交叉韧带损伤模型，随机分为3组干预，空白对照组不进行任何干预，对照组胫骨股骨隧道内移植自体半腱肌肌腱，实验组胫骨股骨隧道内移植自体半腱肌肌腱后再向胫骨隧道内注射骨形态发生蛋白2/Ⅰ型胶原凝胶，移植后3个月，取胫骨骨隧道及近膝关节组织，进行Micro-CT影像学检查、苏木精-伊红染色及Masson染色。
结果与结论：①Micro-CT影像学检查：空白对照组在胫骨隧道开口处、开口近1 cm处及隧道最宽处均未见明显骨组织再生；对照组骨隧道内出现不连续骨再生组织；实验组腱-骨部再生明显，胫骨骨隧道部分区域有连续骨连接；②苏木精-伊红染色：空白对照组骨隧道内可见稀疏纤维组织及骨再生；对照组骨隧道内可见新生骨长入肌腱，但肌腱与周围组织贴服疏松，交界处大量纤维细胞分布，新生骨面积较小；实验组骨隧道内大量新生骨长入肌腱，肌腱与周围骨组织交织分布，新生骨面积较多；③Masson染色：空白对照组腱-骨部未形成，原隧道部分充斥大量脂肪或纤维组织；对照组腱-骨界面可见软骨样组织及纤维组织，但纤维组织排列松散，与软骨组织间无紧密连接；实验组腱-骨部出现纤维组织-软骨-骨组织，纤维组织与软骨组织结合紧密，软骨组织下方为成熟骨组织；④结果表明：骨形态发生蛋白2/Ⅰ型胶原凝胶通过加强骨隧道骨再生和腱-骨结合部愈合促进前交叉韧带损伤的修复。

关键词: 生物材料, 材料相容性, 膝关节, 交叉韧带, 腱-骨愈合, 组织工程, 骨形态发生蛋白2, 广东省自然科学基金

Abstract:

BACKGROUND: No conclusion has yet been drawn on the effect of bone morphogenetic protein-2 (BMP-2)/collagen type I hydrogels on tendon-bone healing during the reconstruction of anterior cruciate ligament (ACL) is inconclusive.
OBJECTIVE: To investigate the effect of BMP-2/collagen type I hydrogels to repair ACL injury.
METHODS: ACL injury models were made in the right knees of 18 New Zealand rabbits. Model rabbits were randomized into three groups: blank control group with no intervention, control group with implantation of autologous semitendinosus tendon into the tibial and femoral tunnels, and experimental group with implantation of autologous semitendinosus tendon into the tibial and femoral tunnels combined with BMP-2/collagen type I hydrogel injection into the tibial tunnel. The Micro-CT, hematoxylin-eosin staining and Masson staining of the tendon-bone interface were conducted at 3 months after implantation.
RESULTS AND CONCLUSION: (1) Micro-CT imaging examination: No obvious bone tissue regeneration around the tibial tunnel (at the opening site, 1 cm distant to the opening site, and at the widest site of the tunnel) was observed in the blank control group. Discontinuous bone regeneration in the tibial tunnel was found in the control group. In the experimental group, there was obvious tendon-bone regeneration and continuous bone connections in part of the tibial tunnel. (2) Hematoxylin-eosin staining: In the blank control group, sparse fibrous tissue and regenerated bone tissue were observed in the bone tunnel. In the control group, new bone tissues grew into the tendon, but the tendon and the surrounding tissue were loose, with a large amount of fibrocytes and the small new bone area. In the experimental group, a large number of new bone tissues were regenerated in the tendon, the tendon was intertwined with the surrounding bone tissues, and the area of new bone was increased. (3) Masson staining: In the blank control group the tunnel was partially filled with fat or fibrous tissues, and no tendon-bone interface appeared. In the control group, cartilage and fibrous tissues were visible on the tendon-bone interface, but the fibrous tissues were loosely arranged and had no close connection with the cartilage tissues. In the experimental group, fibrous-chondral-bone tissues were found on the tendon-bone interface, with fibrous tissues being tightly bound to the cartilage tissues, and mature bone tissues were visible below the cartilage tissue. These results indicate that BMP-2/collagen type I hydrogel is beneficial to ACL repair by strengthening the bone regeneration in the bone tunnel and the healing of tendon-bone junction.

Key words: Bone Morphogenetic Proteins, Anterior Cruciate Ligament, Collagen Type I, Tissue Engineering

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