课题背景：前交叉韧带重建移植肌腱在骨隧道内多为间接愈合，即直接由Sharpey’s纤维固定，且时间长，通常在12周左右，因此早期功能锻炼受到了限制。

应用要点：实验在前交叉韧带重建过程中在骨隧道内加入骨形态发生蛋白2，术后4周发现有类Sharpey纤维和新骨形成，8周时证实有典型的Sharpey’s纤维形成，比以往12周明显提前。

同行评价：骨形态发生蛋白2在前交叉韧带重建过程中对肌腱在骨隧道内的愈合有明显促进作用，促进腱-骨之间形成间接连接，具有重要的临床应用前景。

摘要
目的：前交叉韧带重建移植肌腱在骨隧道内多为间接愈合，即在肌腱与骨之间没有纤维软骨带而直接由Sharpey’s纤维固定。观察人重组骨形态发生蛋白2对移植肌腱在骨隧道内愈合的影响。
方法：实验于2004-06/09在上海市第六人民医院动物实验室完成，动物实验方法符合动物伦理学要求。①实验材料及分组：选用新西兰大白兔36只，按随机数字表法分为3组，即空白对照组、胶原海绵组及骨形态发生蛋白2组，每组12只。②实验方法：采用兔膝关节自体半腱肌重建前交叉韧带悬吊固定模型，骨形态发生蛋白2组在骨隧道内加入人重组骨形态发生蛋白2和胶原海绵，胶原海绵组仅在骨隧道内加入胶原海绵。③实验评估：术后4，8，12周在移植物周围取材进行苏木精-伊红、天狼猩红和Masson染色，观察骨隧道和肌腱移植物间的界面组织学变化，采用Yamakado分类评价界面形态愈合类型，并对Masson染色切片作肌腱周围新骨形成的形态学定量评估。
结果：空白对照组2只白兔于术后第10周脱失。①术后4周空白对照组腱骨间有腱-骨分离，骨形态发生蛋白2组腱-骨间充满结缔组织；术后8周骨形态发生蛋白2组形成Sharpey’s纤维，而空白对照组术后12周时开始出现Sharpey’s纤维。②术后4，8，12周骨形态发生蛋白2组白兔新骨形成面积均显著大于空白对照组、胶原海绵组（P < 0.01）。
结论：人重组骨形态发生蛋白2可促进移植肌腱在骨隧道内的愈合，促进腱-骨之间形成间接连接。
关键词：腱/移植；骨形态发生蛋白质类；骨生成；组织移植

曹红彬，沈灏，蒋垚，辛景义.骨形态发生蛋白2对移植肌腱在骨隧道内愈合的影响：界面组织学特点[J].中国组织工程研究与临床康复，2008，12(2):205-208 [www.zglckf.com/zglckf/ejournal/upfiles/08-2/2k-205(ps).pdf]

Effect of recombinant human bone morphogenetic protein-2 on autograft tendon healing in bone tunnel: Interface histological characteristics

Abstract

AIM：Anterior cruciate ligament reconstruction with semitendonous tendon in bone tunnel always indirectly heals, i.e. there is no fibrocartilagous zone between tendon and bone but Sharpey fiber. The study investigated the effect of recombinant human bone morphogenetic protein-2 (BM-2) on tendon healing in bone tunnel.
METHODS: The experiment was performed in the animal laboratory, Shanghai Sixth People's Hospital from June to September 2004. All the experiment procedures were accorded with the animal ethical requirements. ①Thirty-six New Zealand rabbits were randomly divided into blank control group, collagen sponge group and BMP-2 group with 12 animals in each group. ②Anterior cruciate ligament reconstruction with semitendonous tendon was done in knee joints of rabbits by suspend fixation model. Recombinant human BMP-2 and collagen sponge were implanted in bone tunnel of rats in BMP-2 group, and only collagen sponge was given to collagen sponge group. ③Specimens were collected at 4, 8 and 12 weeks after surgery. Sections were stained with HE, Sirius Red and Masson to observe the changes of interface tissue between bone tunnel and tendon graft. Interface types were classified according to Yamakado method. The amount of new bone formation over the grafted tendon was measured in section with Masson stain for histomorphometry.
RESULTS: Two rabbits in control group dropped from the study at the tenth week. ①At 4 weeks after surgery, tendon-bone separation occurred in control group, while the connective tissue was filled in tendon and bone in BMP-2 group. At 8 weeks, abundant penetrating Sharpey fibers appeared in BMP-2 group but appeared in control group at 12 weeks. ②New bone formation area in BMP-2 group was significantly larger than that in control group and collagen sponge group at 4, 8 and 12 weeks after surgery (P < 0.01).
CONCLUSION: Recombinant human BMP-2 can enhance tendon healing in bone tunnel, and promote the connection between tendon and bone.

Cao HB, Shen H, Jiang Y, Xin JY.Effect of recombinant human bone morphogenetic protein-2 on autograft tendon healing in bone tunnel: Interface histological characteristics.Zhongguo Zuzhi Gongcheng Yanjiu yu Linchuang Kangfu 2008;12(2):205-208(China) [www.zglckf.com/zglckf/ejournal/upfiles/08-2/2k-205(ps).pdf]