Li Dize, Chen Kaiwen, Duan Lian, Fu Tiwei, Li Jiao, Mu Zhixiang, Wang Si, Zou Qin, Chen Li, Feng Yangyingfan, Li Yihan, Zhang Hongmei, Wang Huanan, Chen Tao, Ji Ping
Stomatological Hospital of Chongqing Medical University, Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing Medical University, Chongqing 401147, P. R. China.
School of Life Science and Biotechnology, Dalian University of Technology, Dalian 116023, P. R. China.
ACS Biomater Sci Eng. 2019 Mar 11;5(3):1440-1451. doi: 10.1021/acsbiomaterials.8b01298. Epub 2019 Feb 5.
Osteoporosis is a wide-range disease with a negative impact on bone defect healing. Strontium ranelate (SR) has promising osteogenic potential for its dual function on stimulating osteoblasts and inhibiting osteoclast activity. However, it has limitations for its dose-dependent effect and side effects on systemic applications. Here, a sequentially cross-linking strategy including enzyme-cross-linking through tyrosinase from mushroom and physical folding is acquired to create SR loaded gelatin nanoparticle/silk fibroin aerogel (abbreviated as S/G-Sr-MT) with drug release controlling capacity. The results showed successful enzyme-cross-linking, excellent spatial structure, and enhanced mechanical properties of S/G-Sr-MT. Even Sr loading and stable release with markedly inhibited initial burst release were detected. The biomineralization investigation showed rapid deposition of hydroxyapatite on the surface of S/G-Sr-MT. In vitro, spreading morphology and higher osteogenic gene expression of MC3T3-E1 seeded on S/G-Sr-MT were observed compared to other groups after 7 day culturing. In vivo, S/G-Sr-MT showed an obvious osteogenic capacity in calvaria defects of ovariectomized rats in which high expression and inhibited TRAP activity were observed. Such results suggested the S/G-Sr-MT scaffold could stimulate osteogenic differentiation of osteoblasts while inhibiting osteoclast behaviors in vivo. These findings highlight the potential osteogenic ability and clinical application of SR incorporated enzyme-cross-linked scaffold in ovariectomized (OVX) bone healing.
骨质疏松症是一种广泛存在的疾病，对骨缺损愈合有负面影响。雷奈酸锶（SR）因其对成骨细胞的刺激和破骨细胞活性的抑制双重功能而具有良好的成骨潜力。然而，其在全身应用中的剂量依赖性效应和副作用存在局限性。在此，我们采用了一种包括通过蘑菇酪氨酸酶进行酶交联和物理折叠的顺序交联策略，以制备具有药物释放控制能力的负载SR的明胶纳米颗粒/丝素蛋白气凝胶（简称为S/G-Sr-MT）。结果表明S/G-Sr-MT成功实现了酶交联，具有优异的空间结构和增强的力学性能。检测到均匀的锶负载和稳定释放，且显著抑制了初始突释。生物矿化研究表明羟基磷灰石在S/G-Sr-MT表面快速沉积。在体外，培养7天后，与其他组相比，接种在S/G-Sr-MT上的MC3T3-E1细胞呈现出铺展形态和更高的成骨基因表达。在体内，S/G-Sr-MT在去卵巢大鼠颅骨缺损中显示出明显的成骨能力，观察到其高表达并抑制了抗酒石酸酸性磷酸酶（TRAP）活性。这些结果表明S/G-Sr-MT支架在体内可刺激成骨细胞的成骨分化，同时抑制破骨细胞行为。这些发现突出了含SR的酶交联支架在去卵巢（OVX）骨愈合中的潜在成骨能力和临床应用价值。
