Department of Bone & Joint Surgery, Peking University Shenzhen Hospital, Shenzhen 518036, P.R. China.
National & Local Joint Engineering Research Center of Orthopaedic Biomaterials, Peking University Shenzhen Hospital, Shenzhen 518036, P.R. China.
ACS Appl Mater Interfaces. 2022 Feb 16;14(6):7592-7608. doi: 10.1021/acsami.1c21260. Epub 2022 Feb 4.
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 Mg 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 μm. 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 Mg 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.
天然多糖（NPH）基可注射水凝胶在治疗临界尺寸骨缺损方面显示出巨大的潜力。然而，它们的成骨、血管生成和机械性能仍然不足。在这里，将氧化镁纳米粒子（NPs）掺入新合成的水溶性磷酸肌酸功能化壳聚糖（CSMP）水溶液中，通过 CSMP 中的磷酸基团与 MgO NPs 中的镁之间的超分子组合，形成可注射水凝胶（CSMP-MgO），从而规避了壳聚糖基可注射水凝胶的这些缺点。水溶性壳聚糖偏离 CSMP 首先通过在壳聚糖链上一步冻干过程中接枝甲基丙烯酰基和磷酸肌酸来合成。该水凝胶中的磷酸肌酸不仅提供与 MgO NPs 结合形成超分子结合的位点，而且还作为控制 Mg 释放的储库。结果，冻干 CSMP-MgO 水凝胶呈现出多孔结构，孔壁上有一些小孔，孔径范围为 50 至 100μm。CSMP-MgO 可注射水凝胶在 DI 水中的溶胀受到限制（最低溶胀比为 16.0 ± 1.1 g/g），在压缩时甚至在应变超过 85%（对照组为 28.0 和 41.3 kPa）时也不会发生脆性断裂，具有稳定和持续的调控性 Mg 释放。CSMP-MgO 可注射水凝胶在过饱和磷酸钙溶液中促进钙磷（羟基磷灰石（HA）和四钙磷酸盐（TTCP））沉积，对 MC3T3-E1 细胞无细胞毒性；CSMP-MgO 水凝胶促进 MC3T3-E1 细胞成骨分化，上调 BSP、OPN 和 Osterix 成骨基因表达及矿化和 HUVEC 管形成。其中，CSMP-MgO（5）表现出了大部分这些特性。此外，这种水凝胶（CSMP-MgO（5））在大鼠临界尺寸颅骨缺损中具有优异的促进新骨形成的能力。因此，CSMP-MgO 可注射水凝胶在骨再生方面具有广阔的应用前景。
