Magnesium Oxide Nanoparticle Coordinated Phosphate-Functionalized Chitosan Injectable Hydrogel for Osteogenesis and Angiogenesis in Bone Regeneration
Magnesium Oxide Nanoparticle Coordinated Phosphate-Functionalized Chitosan Injectable Hydrogel for Osteogenesis and Angiogenesis in Bone Regeneration
复制标题
氧化镁纳米颗粒配位的磷酸酯功能化壳聚糖可注射水凝胶用于骨再生中的成骨与血管生成
DOI：
10.1021/acsami.1c21260
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发表时间：
2022-02-04
影响因子：
9.5
通讯作者：
Zeng, Hui
中科院分区：
文献类型：
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作者：
Chen, Yingqi;Sheng, Weibei;Zeng, Hui
基于天然多糖（NPH）的可注射水凝胶在关键尺寸的骨缺损修复中显示出巨大的潜力。然而，它们的成骨、血管生成和机械性能不足。在这里，MgO纳米颗粒（NPs）被纳入到一个新合成的水溶性磷酸肌酸功能化壳聚糖（CSMP）的水溶液中，形成一个可注射的水凝胶（CSMP-MgO）通过超分子结合在CSMP中的磷酸基团和MgO NPs中的镁，以规避这些缺点壳聚糖为基础的可注射的水凝胶。通过一步冻干法将甲基丙烯酸酐和磷酸肌酸接枝到壳聚糖链上，合成了水溶性壳聚糖衍生物CSMP。该水凝胶中的磷酸肌酸不仅提供了与MgO NP联合收割机结合以形成超分子结合的位点，而且还用作控制Mg 2+释放的储库。结果表明，冻干的CSMP-MgO水凝胶呈多孔结构，孔壁中有一些小孔，孔径范围为50 - 100 μ m。CSMP-MgO可注射水凝胶在去离子水中的溶胀受到限制（最低溶胀比为16.0 +/-1.1g/g），并且在压缩过程中即使在高于85%的应变下也不呈现脆性破坏（最大抗压强度为195.0 kPa）与对照组相比（对于CSMP和CSMP-MgO（0.5）水凝胶为28.0和41.3kPa），具有以稳定和持续的方式调节的Mg 2+释放。CSMP-MgO可注射水凝胶促进体外磷酸钙（羟基磷灰石（HA）和磷酸四钙（TTCP））在过饱和磷酸钙溶液中沉积，并且对MC 3 T3-E1细胞没有细胞毒性; CSMP-MgO水凝胶促进MC 3 T3-E1细胞成骨分化，上调BSP、OPN和Osterix成骨基因表达和矿化以及HUVEC管形成。其中CSMP-MgO（5）具有上述性质。此外，该水凝胶（CSMP-MgO（5））显示出促进大鼠中临界尺寸颅骨缺损中新骨形成的优异能力。因此，CSMP-MgO可注射水凝胶显示出用于骨再生的巨大前景。
Natural polysaccharide (NPH)-based injectable hydrogels have shown great potential for critical-sized bone defect repair. However, their osteogenic, angiogenic, and mechanical properties are insufficient. Here, MgO nanoparticles (NPs) were incorporated into a newly synthesized water-soluble phosphocreatine-functionalized chitosan (CSMP) water solution to form an injectable hydrogel (CSMP-MgO) via supramolecular combination between phosphate groups in CSMP and magnesium in MgO NPs to circumvent these drawbacks of chitosan-based injectable hydrogels. Water-soluble chitosan deviate CSMP was first synthesized by grafting methacrylic anhydride and phosphocreatine into a chitosan chain in a one-step lyophilization process. The phosphocreatine in this hydrogel not only provides sites to combine with MgO NPs to form supramolecular binding but also serves as the reservoir to control Mg2+ release. As a result, the lyophilized CSMP-MgO hydrogels presented a porous structure with some small holes in the pore wall, and the pore diameters ranged from 50 to 100 mu m. The CSMP-MgO injectable hydrogels were restricted from swelling in DI water (lowest swelling ratio was 16.0 +/- 1.1 g/g) and presented no brittle failure during compression even at a strain above 85% (maximum compressive strength was 195.0 kPa) versus the control groups (28.0 and 41.3 kPa for CSMP and CSMP-MgO (0.5) hydrogels), with regulated Mg2+ release in a stable and sustained manner. The CSMP-MgO injectable hydrogels promoted in vitro calcium phosphate (hydroxyapatite (HA) and tetracalcium phosphate (TTCP)) deposition in supersaturated calcium phosphate solution and presented no cytotoxicity to MC3T3-E1 cells; the CSMP-MgO hydrogel promoted MC3T3-E1 cell osteogenic differentiation with upregulation of BSP, OPN, and Osterix osteogenic gene expression and mineralization and HUVEC tube formation. Among them, CSMP-MgO (5) presented most of these properties. Moreover, this hydrogel (CSMP-MgO (5)) showed an excellent ability to promote new bone formation in critical-sized calvarial defects in rats. Thus, the CSMP-MgO injectable hydrogel shows great promise for bone regeneration.