基于丝/硅酸钙/海藻酸钠复合支架的肌源性鸢尾素递送载体用于骨再生。
Delivery vehicle of muscle-derived irisin based on silk/calcium silicate/sodium alginate composite scaffold for bone regeneration.
机构信息
Department of Prosthodontics, Shanghai Engineering Research Center of Advanced Dental Technology and Materials, Shanghai Key Laboratory of Stomatology and Shanghai Research Institute of Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, China,
The State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, China.
出版信息
Int J Nanomedicine. 2019 Feb 22;14:1451-1467. doi: 10.2147/IJN.S193544. eCollection 2019.
BACKGROUND
Irisin is a cytokine produced by skeletal muscle and usually plays a pivotal role in inducing fat browning and regulating energy expenditure. In recent years, it was found that irisin might be the molecular entity responsible for muscle-bone connectivity and is useful in osteogenesis induction.
MATERIALS AND METHODS
To study its effect on bone regeneration, we developed silk/calcium silicate/sodium alginate (SCS) composite scaffold based on an interpenetrating network hydrogel containing silk fibroin, calcium silicate, sodium alginate. Then we loaded irisin on the SCS before coating it with polyvinyl alcohol (PVA). The SCS/P scaffold was physically characterized and some in vitro and in vivo experiments were carried out to evaluate the scaffold effect on bone regeneration.
RESULTS
The SCS/P scaffold was showed a porous sponge structure pursuant to scanning electron microscopy analysis. The release kinetics assay demonstrated that irisin was stably released from the irisin-loaded hybrid system (i/SCS/P system) to 50% within 7 days. Moreover, osteoinductive studies using bone marrow stem cells (BMSCs) in vitro exhibited the i/SCS/P system improved the activity of alkaline phosphatase (ALP) and enhanced the expression levels of a series of osteogenic markers containing Runx-2, ALP, BMP2, Osterix, OCN, and OPN. Alizarin red staining also demonstrated the promotion of osteogenesis induced by i/SCS/P scaffolds. In addition, in vivo studies showed that increased bone regeneration with better mineralization and higher quality was found during the repair of rat calvarial defects through utilizing the i/SCS/P system.
CONCLUSION
These data provided strong evidence that the composite i/SCS/P would be a promising substitute for bone tissue engineering.
背景
鸢尾素是一种由骨骼肌产生的细胞因子，通常在诱导脂肪棕色化和调节能量消耗方面发挥关键作用。近年来，发现鸢尾素可能是肌肉-骨骼连接的分子实体，并且在成骨诱导中很有用。
材料和方法
为了研究其对骨再生的影响，我们开发了基于丝素蛋白、硅酸钙、海藻酸钠的互穿网络水凝胶的丝/硅酸钙/海藻酸钠（SCS）复合支架。然后，我们在 SCS 上加载鸢尾素，再用聚乙烯醇（PVA）进行涂层。对 SCS/P 支架进行物理特性分析，并进行了一些体外和体内实验，以评估支架对骨再生的影响。
结果
扫描电子显微镜分析表明，SCS/P 支架呈现多孔海绵结构。释放动力学研究表明，鸢尾素从负载鸢尾素的混合系统（i/SCS/P 系统）中以 50%的速率稳定释放，7 天内达到 7 天内达到 50%。此外，体外骨髓间充质干细胞（BMSCs）的成骨诱导研究表明，i/SCS/P 系统提高了碱性磷酸酶（ALP）的活性，并增强了一系列成骨标志物的表达水平，包括 Runx-2、ALP、BMP2、Osterix、OCN 和 OPN。茜素红染色也证明了 i/SCS/P 支架促进了成骨。此外，体内研究表明，在通过使用 i/SCS/P 系统修复大鼠颅骨缺损时，发现骨再生增加，矿化更好，质量更高。
结论
这些数据提供了有力的证据，表明复合 i/SCS/P 将是一种有前途的骨组织工程替代物。
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