Injectable tissue-engineered bone repair of a rat calvarial defect.

Injectable tissue-engineered bone repair of a rat calvarial defect.
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DOI:
10.1002/lary.20624
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发表时间:
2010-05
期刊:
影响因子:
2.6
通讯作者:
Park, Stephen S.
Park, Stephen S.
中科院分区:
医学2区
文献类型:
--
作者:
Stephan, Scott J.;Tholpady, Sunil S.;Gross, Brian;Petrie-Aronin, Caren E.;Botchway, Edward A.;Nair, Lakshmi S.;Ogle, Roy C.;Park, Stephen S.

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骨修复方面的进展主要集中在组织工程骨(TEB)的微创输送方面。以间充质干细胞(MSCs)和骨生长因子(BMP-2)为载体,构建了一种新型的壳聚糖-无机磷酸盐生物聚合物,并在大鼠颅骨临界大小缺损(CSD)模型上进行了评价。绿色荧光蛋白(GFP)标记的MSCs用于评估细胞的存活和增殖模式。动物模型的前瞻性对照试验。30只雄性大鼠制作8 mm颅骨CSD,分为5组,每组6只。实验组植入壳聚糖凝胶、骨髓间充质干细胞凝胶(0.3×106个/缺损处)、骨形态发生蛋白-2凝胶(2µg/缺损处)或同时植入骨髓间充质干细胞和骨形态发生蛋白-2的凝胶。在对照组中,缺损处不进行处理。4周后行体内微CT分析。8周后取颅骨标本进行显微CT、组织学和免疫组织化学检查。在所有处理的动物的缺损处都可以看到新的骨生长区域。Micro-CT分析显示,与所有其他组相比,Gel/MSC/BMP-2处理组的骨体积和骨面积的再生显著(P<.001)随时间的增加而增加。组织学分析证实了这种差异。在新骨区域检测到GFP标记的TEB,表明细胞活性和注射的MSC对新骨生长的贡献。这项研究表明,使用壳聚糖凝胶、MSC和BMP-2的可注射形式的TEB可以促进大鼠颅骨CSD的骨形成。
Advances in bone repair have focused on the minimally-invasive delivery of tissue-engineered bone (TEB). A promising injectable biopolymer of chitosan and inorganic phosphates was seeded with mesenchymal stem cells (MSCs) and a bone growth factor (BMP-2), and evaluated in a rat calvarial critical size defect (CSD). Green fluorescent protein (GFP)-labeled MSCs are used to evaluate patterns of cell viability and proliferation. Prospective, controlled trial in an animal model. In 30 male rats, 8-mm calvarial CSDs were created, and divided into five groups of six animals each. In the experimental groups, the defects were injected with either chitosan gel, gel loaded with MSCs (0.3 × 106 cells/defect), gel loaded with BMP-2 (2 µg/defect), or gel loaded with both MSC and BMP-2. In the control group, the defect was left untreated. At 4 weeks, in vivo microcomputed tomography (micro-CT) analysis was performed. At 8 weeks, calvarial specimens were examined by micro-CT, histology, and immunohistochemistry. New areas of bone growth were seen in the defects of all treated animals. Micro-CT analysis revealed a significant (P < .001) time-dependent increase in the regeneration of bone volume and bone area in defects treated with gel/MSC/BMP-2 as compared to all other groups. Histological analysis confirmed this difference. GFP–labeled TEB was detected within the areas of new bone, indicating cell viability and contribution to new bone growth by the injected MSC. This study demonstrates that an injectable form of TEB using a chitosan gel, MSC, and BMP-2 can enhance bone formation in a rat calvarial CSD.
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