Strontium Ranelate Incorporated Enzyme-Cross-Linked Gelatin Nanoparticle/Silk Fibroin Aerogel for Osteogenesis in OVX-Induced Osteoporosis
Strontium Ranelate Incorporated Enzyme-Cross-Linked Gelatin Nanoparticle/Silk Fibroin Aerogel for Osteogenesis in OVX-Induced Osteoporosis
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雷尼酸锶掺入酶交联明胶纳米颗粒/丝素蛋白气凝胶用于 OVX 诱导的骨质疏松症的成骨
DOI：
10.1021/acsbiomaterials.8b01298
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发表时间：
2019-03-01
影响因子：
5.8
通讯作者：
Ji, Ping
中科院分区：
文献类型：
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作者：
Li, Dize;Chen, Kaiwen;Ji, Ping
骨质疏松症是一种广泛的疾病，对骨缺损的愈合有负面影响。雷尼酸锶(SR)具有刺激成骨细胞和抑制破骨细胞活性的双重功能，具有良好的成骨潜能。然而，由于其剂量依赖效应和对全身应用的副作用，它具有局限性。在这里，通过蘑菇酪氨酸酶和物理折叠的顺序交联策略，制备了具有药物释放控制能力的SR负载明胶纳米粒子/丝素蛋白气凝胶(简称S/G-SR-MT)。结果表明，S/G-SR-MT复合材料酶交联成功，空间结构良好，力学性能得到提高。Sr2+负载均匀，释放量稳定，初期突释受到明显抑制。生物矿化研究表明，羟基磷灰石迅速沉积在S/G-SR-MT表面。体外培养7d后，观察到MC3T3EL在S/G-sr-MT上的铺展形态和成骨基因的高表达。体内实验显示，S/G-sr-MT对去卵巢大鼠颅骨缺损区具有明显的成骨能力，表现为高表达Runx2和抑制TRAP活性。上述结果提示，S/G-锶-MT支架在体内可促进成骨细胞的成骨分化，同时抑制破骨细胞的行为。这些发现突出了SR复合酶交联支架在卵巢切除(OVX)骨愈合中的潜在成骨能力和临床应用。
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 Sr2+ 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 MC3T3El 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 Runx2 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.