Bone defects are a common and challenging orthopedic problem with poor self-healing ability and long treatment cycles. The difficult-to-heal bone defects cause a significant burden of medical expenses on patients. Currently, biomaterials with mechanical stability, long-lasting action, and osteogenic activity are considered as a suitable way to effectively heal bone defects. Here, an injectable double network (DN) hydrogel prepared using physical and chemical cross-linking methods is designed. The first rigid network is constructed using methylpropenylated hyaluronic acid (HAMA), while the addition of chitosan oligosaccharide (COS) forms a second flexible network by physical cross-linking. The mesoporous silica nanoparticles (MSN) loaded with bone morphogenetic protein-4 (BMP-4) were embedded into DN hydrogel, which not only enhanced the mechanical stability of the hydrogel, but also slowly released BMP-4 to achieve long-term skull repair. The designed composite hydrogel showed an excellent compression property and deformation resistance. In vitro studies confirmed that the HAMA/COS/MSN@BMP-4 hydrogel had good biocompatibility and showed great potential in supporting proliferation and osteogenic differentiation of mouse embryo osteoblast precursor (MC3T3-E1) cells. Furthermore, in vivo studies confirmed that the DN hydrogel successfully filled and closed irregular skull defect wounds, effectively promoted bone regeneration, and significantly promoted bone repair compared with the control group. In addition, HAMA/COS/MSN@BMP-4 hydrogel precursor solution can quickly form hydrogel in situ at the wound by ultraviolet light, which can be applied to the closure and repair of wounds of different shapes, which provides the new way for the treatment of bone defects.

中文翻译：

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由介孔二氧化硅纳米颗粒增强并负载 BMP-4 的可注射原位形成双网络水凝胶用于颅骨缺损的闭合和修复

骨缺损是一种常见且具有挑战性的骨科问题，其自愈能力差、治疗周期长。难以愈合的骨缺损给患者带来了巨大的医疗费用负担。目前，具有机械稳定性、持久作用和成骨活性的生物材料被认为是有效治愈骨缺损的合适方法。这里，设计了一种使用物理和化学交联方法制备的可注射双网络（DN）水凝胶。第一个刚性网络是使用甲基丙烯酰化透明质酸（HAMA）构建的，而添加壳寡糖（COS）通过物理交联形成第二个柔性网络。将负载骨形态发生蛋白4（BMP-4）的介孔二氧化硅纳米颗粒（MSN）嵌入DN水凝胶中，不仅增强了水凝胶的机械稳定性，而且缓慢释放BMP-4以实现长期颅骨修复。设计的复合水凝胶表现出优异的压缩性能和抗变形能力。体外研究证实HAMA/COS/MSN@BMP-4水凝胶具有良好的生物相容性，在支持小鼠胚胎成骨前体细胞（MC3T3-E1）增殖和成骨分化方面显示出巨大潜力。此外，体内研究证实，DN水凝胶成功填充和闭合不规则颅骨缺损创面，有效促进骨再生，与对照组相比显着促进骨修复。此外，HAMA/COS/MSN@BMP-4水凝胶前驱体溶液可利用紫外光在伤口处快速原位形成水凝胶，可应用于不同形状伤口的闭合和修复，为伤口愈合提供了新途径。骨缺损的治疗。