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A novel photocrosslinked phosphate functionalized Chitosan-Sr5(PO4)2SiO4 composite hydrogels and in vitro biomineralization, osteogenesis, angiogenesis for bone regeneration application
Composites Part B: Engineering ( IF 12.7 ) Pub Date : 2021-06-05 , DOI: 10.1016/j.compositesb.2021.109057
Yingqi Chen , Anjaneyulu Udduttula , Xuelin Xie , Meng Zhou , Weibei Sheng , Fei Yu , Jian Weng , Deli Wang , Bin Teng , Geetha Manivasagam , Jian V. Zhang , Pei-Gen Ren , Bin Kang , Hui Zeng

The natural polysaccharide-based hydrogels have gained significant interest to use as 3D scaffolds for bone repair and reconstruction owing to their excellent biocompatibility, biosafety, and biodegradability. Yet, these hydrogels have major obstacles in terms of insufficient properties such as mechanical, osteogenic, angiogenic, and biomineralization. Therefore, this study mainly aims to develop an innovative water-soluble phosphate functionalized chitosan (CSMAP) through consequent modification with methacrylic anhydride (MA), then alteration by phosphonopropionic acid (P). Further, a novel photocrosslinked composite hydrogel was fabricated with a combination of CSMAP and synthesized strontium phosphosilicate (SPS, Sr5(PO4)2SiO4) bioceramic nanoparticles with a photoinitiator under UV irradiation. The various concentrations of nanosized SPS particles (0.5, 2.5, 5, and 10 mg/mL) were incorporated into the CSMAP matrix and the swelling, mechanical, morphological, physiochemical, osteogenic, angiogenic properties were investigated. The CSMAP-SPS composite hydrogels possessed a well-arranged porous network structure. The composite hydrogel was restricted to swell in distilled water with the increased concentration of SPS particles. The compressive strength and modulus of CSMAP hydrogel were improved by the inclusion of SPS particles. The bioactive Sr, P, and Si ions were released from CSMAP-SPS hydrogels in a sustained and controlled manner at a non-toxic level. The composite hydrogels promoted in vitro amorphous apatite deposition, revealing a superior biomineralization activity. In vitro results demonstrated that the composites hydrogels showed no toxicity to preosteoblast MC3T3-E1 cells, induced MC3T3-E1 osteogenic differentiation with detection of bsp, ocn and opn osteogenic genes, and also promoted the endothelial tube formation with increased capillary length, branch points, and angiogenic gene vegf expression. Thus, the obtained results proved that the fabricated novel CSMAP-SPS hydrogel could act as an attractive candidate for bone regeneration.



中文翻译:

一种新型光交联磷酸盐功能化壳聚糖-Sr 5 (PO 4 ) 2 SiO 4复合水凝胶和用于骨再生的体外生物矿化、成骨、血管生成

天然多糖基水凝胶由于其优异的生物相容性、生物安全性和生物降解性而被用作骨修复和重建的 3D 支架。然而,这些水凝胶在机械、成骨、血管生成和生物矿化等性能不足方面存在重大障碍。因此,本研究的主要目的是通过随后用甲基丙烯酸酐(MA)进行改性,然后用膦酰基丙酸(P)进行改性,开发一种创新的水溶性磷酸盐功能化壳聚糖(CSMAP)。此外,一种新型光交联复合水凝胶由 CSMAP 和合成的磷硅酸锶 (SPS, Sr 5 (PO 4 ) 2 SiO 4)在紫外线照射下带有光引发剂的生物陶瓷纳米颗粒。将各种浓度的纳米 SPS 颗粒(0.5、2.5、5 和 10 mg/mL)加入到 CSMAP 基质中,并研究了膨胀、机械、形态、生理化学、成骨、血管生成特性。CSMAP-SPS 复合水凝胶具有排列良好的多孔网络结构。随着 SPS 颗粒浓度的增加,复合水凝胶被限制在蒸馏水中膨胀。CSMAP 水凝胶的压缩强度和模量通过包含 SPS 颗粒得到改善。生物活性 Sr、P 和 Si 离子以持续和受控的方式从 CSMAP-SPS 水凝胶中以无毒水平释放。体外促进复合水凝胶无定形磷灰石沉积,显示出优异的生物矿化活性。体外结果表明,复合水凝胶对前成骨细胞 MC3T3-E1 细胞无毒性,通过检测bspocnopn成骨基因诱导 MC3T3-E1 成骨分化,并通过增加毛细血管长度、分支点、和血管生成基因vegf表达。因此,获得的结果证明制造的新型 CSMAP-SPS 水凝胶可以作为骨再生的有吸引力的候选者。

更新日期:2021-06-08
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