TCP/PLGA composite scaffold loaded rapamycin in situ enhances lumbar fusion by regulating osteoblast and osteoclast activity
TCP/PLGA composite scaffold loaded rapamycin in situ enhances lumbar fusion by regulating osteoblast and osteoclast activity
复制标题
TCP/PLGA复合支架原位负载雷帕霉素通过调节成骨细胞和破骨细胞活性增强腰椎融合
DOI：
10.1002/term.3186
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发表时间：
2021-04-19
影响因子：
3.3
通讯作者：
Cai，Daozhang
中科院分区：
文献类型：
--
作者：
Liu，Hai;Zhu，Huangrong;Cai，Daozhang
本研究的目的是开发一种新型的β-磷酸三钙（TCP）/聚（D，L-乳酸-羟基乙酸）（PLGA）复合支架，负载雷帕霉素，可以调节成骨细胞和破骨细胞的活性，用于腰椎融合。通过低温三维打印技术制备TCP/PLGA复合支架，然后原位负载雷帕霉素。扫描电镜观察复合支架的表面结构形态。为评价该复合支架的体外生物相容性，将骨髓间充质干细胞（BMSCs）在TCP/PLGA复合支架玻片上进行培养，并采用活/死细胞活性试剂盒（LiveDeadViabilityKit）进行检测。采用免疫组化染色和Western blotting方法观察雷帕霉素对破骨细胞和成骨细胞的影响。体外实验结果表明，载雷帕霉素的TCP/PLGA复合支架与BMSC具有良好的生物相容性，释放的雷帕霉素明显促进了成骨细胞的分化和矿化。体内研究将负载雷帕霉素的TCP/PLGA复合支架植入腰椎融合模型，通过显微CT扫描、苏木精-伊红、Masson染色、免疫组织化学染色等方法，评价雷帕霉素对骨融合的影响。体内实验结果表明，载雷帕霉素的TCP/PLGA复合支架可分别通过调节成骨细胞和破骨细胞的活性来促进骨形成。在本研究中，负载雷帕霉素的TCP/PLGA复合支架被证实提供了良好的相容性，并通过调节成骨细胞和骨细胞活性来改善腰椎融合的性能，将是一种有前途的骨组织工程复合生物材料。
The purpose of this study was to develop a novel β‐tricalcium phosphate (TCP)/poly (D,L‐lactic‐co‐glycolic acid) (PLGA) composite scaffold loaded with rapamycin that can regulate the activity of osteoblasts and osteoclasts for lumbar fusion. The TCP/PLGA composite scaffold was fabricated by cryogenic three‐dimensional printing techniques and then loaded with rapamycin in situ. The structural surface morphology of the composite scaffold was tested with scanning electron microscope. To evaluate the biocompatibility of the composite scaffold in vitro, bone marrow mesenchymal stem cells (BMSCs) were cultured on the TCP/PLGA composite scaffold slide and tested with Live/Dead Viability Kit. The effect of rapamycin on osteoclast and osteoblast was studied with staining and Western blotting. The in vitro results showed that the rapamycin‐loaded TCP/PLGA composite scaffold showed good biocompatibility with BMSC and released rapamycin obviously promoted the osteoblast differentiation and mineralization. In vivo study, the TCP/PLGA composite scaffold loaded with rapamycin were implanted in lumbar fusion model and study with micro‐computed tomography scanning, hematoxylin–eosin, Masson, and immune‐histological staining, to evaluate the effect of rapamycin on bone fusion. The in vivo results demonstrated that rapamycin‐loaded TCP/PLGA composite scaffold could enhance bone formation by regulating osteoblast and osteoclast activity, respectively. In this study, the TCP/PLGA composite scaffold loaded with rapamycin was confirmed to provide great compatibility and improved performance in lumbar fusion by regulating osteoblastic and osteoclastic activity and would be a promising composite biomaterial for bone tissue engineering.