HA/MgO nanocrystal-based hybrid hydrogel with high mechanical strength and osteoinductive potential for bone reconstruction in diabetic rats
HA/MgO nanocrystal-based hybrid hydrogel with high mechanical strength and osteoinductive potential for bone reconstruction in diabetic rats
复制标题
HA/MgO纳米晶混合水凝胶具有高机械强度和骨诱导潜力，可用于糖尿病大鼠骨重建
DOI：
10.1039/d0tb02553d
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发表时间：
2021-01-28
影响因子：
7
通讯作者：
Yuan, Jian-Dong
中科院分区：
文献类型：
--
作者：
Chen, Rui;Chen, Hang-Bo;Yuan, Jian-Dong
糖尿病(DM)患者的骨修复和再生过程明显受损。类似于为正常愈合条件开发的干预方法已被用于对抗糖尿病相关的骨再生。然而，这些方法取得的成果有限。因此，将骨诱导氧化镁纳米晶与骨传导羟基磷灰石(HA)纳米晶均匀地安装在由半胱氨酸修饰的聚谷氨酸(PGA-Cys)组成的有机水凝胶的网络基质中，构建了一种杂化粗糙的水凝胶支架。推测羟基磷灰石/氧化镁纳米晶杂化水凝胶(HA/MgO-H)支架可通过控制释放镁离子来显著促进糖尿病大鼠的骨修复。与PGA-Cys支架相比，HA/MgO-H支架呈海绵状，内部有多孔的三维网络，具有更高的机械强度。同时，羟基磷灰石/氧化镁-H支架水化后逐渐形成G‘大于1000Pa的韧性水凝胶，并保持了较高的水化膨胀率。此外，在分散的氧化镁纳米晶化学降解后，由于镁离子与PGA-Cys的羧基之间的络合作用，镁离子从水凝胶基质中缓慢释放长达8周。体外细胞研究表明，HA/MgO-H支架不仅能有效促进BMSCs的迁移和增殖，还能诱导其向成骨细胞分化。此外，将HA/MgO-H支架植入DM大鼠股骨缺损区后8周，显微CT显示骨修复效果更好。骨密度(397.22+/-16.36 mg cm(-3))、骨小梁厚度(0.48+/-0.07 mm)、骨组织体积/总组织体积(79.37+/-7.96%)均显著高于其他两组。此外，HA/MgO-H处理后，Col-I和OCN的表达也增加。HA/MgO-H支架的骨修复机制与炎性巨噬细胞(CD80(+))的减少和血管生成(CD31(+))的增加密切相关。综上所述，不使用生物活性因子的羟基磷灰石/氧化镁-H支架有望成为一种促进糖尿病骨缺损愈合的生物材料。
Bone repair and regeneration processes are markedly impaired in diabetes mellitus (DM). Intervening approaches similar to those developed for normal healing conditions have been adopted to combat DM-associated bone regeneration. However, limited outcomes were achieved for these approaches. Hence, together with osteoconductive hydroxyapatite (HA) nanocrystals, osteoinductive magnesium oxide (MgO) nanocrystals were uniformly mounted into the network matrix of an organic hydrogel composed of cysteine-modified gamma-polyglutamic acid (PGA-Cys) to construct a hybrid and rough hydrogel scaffold. It was hypothesized that the HA/MgO nanocrystal hybrid hydrogel (HA/MgO-H) scaffold can significantly promote bone repair in DM rats via the controlled release of Mg2+. The HA/MgO-H scaffold exhibited a sponge-like morphology with porous 3D networks inside it and displayed higher mechanical strength than a PGA-Cys scaffold. Meanwhile, the HA/MgO-H scaffold gradually formed a tough hydrogel with G ' of more than 1000 Pa after hydration, and its high hydration swelling ratio was still retained. Moreover, after the chemical degradation of the dispersed MgO nanocrystals, slow release of Mg2+ from the hydrogel matrix was achieved for up to 8 weeks because of the chelation between Mg2+ and the carboxyl groups of PGA-Cys. In vitro cell studies showed that the HA/MgO-H scaffold could not only effectively promote the migration and proliferation of BMSCs but could also induce osteogenic differentiation. Moreover, in the 8th week after implanting the HA/MgO-H scaffold into femur bone defect zones of DM rats, more effective bone repair was presented by micro-CT imaging. The bone mineral density (397.22 +/- 16.36 mg cm(-3)), trabecular thickness (0.48 +/- 0.07 mm), and bone tissue volume/total tissue volume (79.37 +/- 7.96%) in the HA/MgO-H group were significantly higher than those in the other groups. Moreover, higher expression of COL-I and OCN after treatment with HA/MgO-H was also displayed. The bone repair mechanism of the HA/MgO-H scaffold was highly associated with reduced infiltration of pro-inflammatory macrophages (CD80(+)) and higher angiogenesis (CD31(+)). Collectively, the HA/MgO-H scaffold without the usage of bioactive factors may be a promising biomaterial to accelerate bone defect healing under diabetes mellitus.