A novel photocrosslinked phosphate functionalized Chitosan-Sr5(PO4)2SiO4 composite hydrogels and in vitro biomineralization, osteogenesis, angiogenesis for bone regeneration application
A novel photocrosslinked phosphate functionalized Chitosan-Sr5(PO4)2SiO4 composite hydrogels and in vitro biomineralization, osteogenesis, angiogenesis for bone regeneration application
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DOI：
10.1016/j.compositesb.2021.109057
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发表时间：
2021-06-08
影响因子：
13.1
通讯作者：
Zeng, Hui
中科院分区：
文献类型：
--
作者：
Chen, Yingqi;Udduttula, Anjaneyulu;Zeng, Hui
天然多糖基水凝胶由于其优异的生物相容性、生物安全性和生物可降解性，作为骨修复和重建的3D支架获得了极大的兴趣。然而，这些水凝胶在诸如机械、成骨、血管生成和生物矿化的性能不足方面具有主要障碍。因此，本研究主要目的是开发一种创新的水溶性磷酸功能化壳聚糖（CSMAP），通过后续的甲基丙烯酸酐（MA）的改性，然后改变膦酰基丙酸（P）。此外，在紫外光照射下，CSMAP和合成的磷硅酸锶（SPS，Sr 5（PO 4）2SiO 4）生物陶瓷纳米粒子与光引发剂的组合制备了一种新型的光交联复合水凝胶。将不同浓度的纳米SPS颗粒（0.5、2.5、5和10 mg/mL）掺入CSMAP基质中，并研究其溶胀、机械、形态学、生理化学、成骨、血管生成特性。CSMAP-SPS复合水凝胶具有有序的多孔网络结构。随着SPS粒子浓度的增加，复合水凝胶在蒸馏水中的溶胀受到限制。SPS粒子的加入提高了CSMAP水凝胶的压缩强度和模量。生物活性的Sr，P，和Si离子从CSMAP-SPS水凝胶中以持续和受控的方式在无毒水平下释放。复合水凝胶促进了体外无定形磷灰石沉积，显示出优越的上级生物矿化活性。体外实验结果表明，复合水凝胶对前成骨细胞MC 3 T3-E1细胞无毒性，诱导成骨细胞分化（bsp、ocn和opn成骨基因检测），并促进内皮管形成（毛细血管长度增加、分支点增多、血管生成基因vegf表达增加）。因此，所获得的结果证明，所制造的新型CSMAP-SPS水凝胶可以作为骨再生的有吸引力的候选物。
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.