课题背景：各种基质材料单独应用时成骨能力有限，为增强材料的成骨能力，将支架材料、成骨细胞和生长因子等复合构成复合材料用于骨移植已成为目前植骨材料的研究方向。四环素可吸附在矿物质表面、丙稀酸脂链、可吸收纤维素、交联胶原膜上，并可以持续释放。实验利用四环素吸附在矿物质和胶原膜上发挥作用的特性，将四环素吸附于胶原生物衍生骨复合材料，从而构建新型生物衍生骨材料。

应用要点：①以体外培养的兔成骨细胞为种子细胞，四环素-胶原生物衍生骨缓释材料为支架材料成功构建四环素-胶原生物衍生骨复合材料，提示四环素可用于构建组织工程骨材料。②阳性对照的实验结果提示，四环素能够为骨组织再生提供类生长因子样功能。

偏倚或不足：四环素-胶原生物衍生骨缓释材料，是一种较为理想的类生长因子载体材料。但将其植入机体后可能出现骨沉积反应，对骨形成产生影响。因此，合适剂量的四环素对于四环素-胶原生物衍生骨缓释材料促进骨再生起决定性作用。

摘要

背景：各种基质材料单独应用时成骨能力有限，为增强材料的成骨能力，应用复合材料修复骨缺损是组织工程的发展方向。
目的：探讨四环素-胶原生物衍生骨材料植入体内后的成骨能力。
设计、时间及地点：于2004-09/2005-01在四川大学华西医学中心组织工程实验室完成随机分组设计的对照观察实验。
材料：选择新西兰大白兔24只，按随机数字表法分为2组，每组12只。制备兔桡骨中段1.5 cm骨缺损模型。新鲜人骨自行制备四环素-胶原衍生骨材料。
方法：将两种材料分别植入兔桡骨缺损部位。实验组为四环素-胶原生物衍生骨，对照组为胶原生物衍生骨。术后6，12周动物麻醉后处死取材。
主要观察指标：X射线观察和组织学检测缺损部位的成骨情况。
结果：纳入动物24只，均进入结果分析。①X射线结果：术后6周，实验组整个缺损区均可见到骨痂生成，对照组仅在缺损两端有骨痂生成。术后12周，实验组缺损部位已完全被新生成骨组织所填充，与自体骨基本相近，已有骨髓腔出现，对照组骨缺损区可见明显的骨生成影像。②组织学结果：术后6周，实验组在材料内部孔隙区可见到新生类骨质形成，对照组缺损区无骨组织形成。术后12周，实验组可见大量的编织骨样组织，已形成板层骨样结构，骨髓腔已贯通，对照组缺损区可见有骨样组织形成。
结论：胶原生物衍生骨与四环素-胶原生物衍生骨材料均可促进骨再生，四环素-胶原生物衍生骨材料对兔骨缺损修复效果优于胶原生物衍生骨材料。
关键词：四环素；骨缺损；组织工程；生物材料

梁军，辛景义，曹红彬.四环素-胶原生物衍生骨缓释材料修复骨缺损[J].中国组织工程研究与临床康复，2008，12(14):2615-2618
[www.zglckf.com/zglckf/ejournal/upfiles/08-14/14k-2615(ps).pdf]

Tetracycline loaded bio-derived bone to repair bone defect

Abstract

BACKGROUND:Compound materials have strong osteogenic ability, which reinforce the substitute materials used alone. Compound material will be commonly used to repair bone defects in tissue engineering.
OBJECTIVE: To explore the osteogenic capacity of tetracycline loaded bio-derived bone in vivo.
DESIGN, TIME AND SETTING: The randomized controlled observation was performed at Tissue Engineering Laboratory (State Key Laboratory) of West China Center of Medical Sciences, Sichuan University from September 2004 to January 2005.
MATERIALS: Twenty-four New Zealand white rabbits were randomly divided into 2 groups (n=12). Rabbit models of radial middle segment defect (1.5 cm) were established. Tetracycline collagen bio-derived bone was made of fresh human bone.
METHODS: The tetracycline collagen bio-derived bone was implanted into radial defects of experimental group, and collagen bio-derived bone was implanted into control group. All rabbits were executed 6 and 12 weeks after operation.
MAIN OUTCOME MEASURES: Osteogenic condition in all specimens was examined by X-ray and histological methods.
RESULTS: Twenty-four animals were included in final analysis. ①X-ray results showed that osteotylus was seen in the whole defect area of the experimental group in postoperative 6 weeks, while only in the defect ends of the control group. In 12 weeks after surgery, new bone tissue filled all defect area of the experimental group, which was basically consistent with normal bone, even medullary canal was formed. Osteogenic images were found in the control group. ②Histological results suggested that new osteoid formation was observed in internal pore zone in the experimental group in 6 weeks, while no bone tissue was found in the control group. In 12 weeks, much woven bone was seen in the experimental group, and lamellar bone structure had formed and medullary cavity of bones had transfixed. Osteoid formation was observed in the control group.
CONCLUSION: Both tetracycline collagen bio-derived bone and collagen bio-derived bone can promote bone formation, but tetracycline loaded bio-derived materials show superior effect in repairing defects.

Liang J, Xin JY, Cao HB.Tetracycline loaded bio-derived bone to repair bone defect.Zhongguo Zuzhi Gongcheng Yanjiu yu Linchuang Kangfu 2008;12(14):2615-2618 [www.zglckf.com/zglckf/ejournal/upfiles//08-14/14k-2615 (ps).pdf]