Sulfated polysaccharides are attractive semi-synthesized materials that can be used as a mimic of heparan sulfate to modulate the protein activity and other physiological processes. In this study, we employed sulfated chitosan to enhance the angiogenic capacity of bone morphogenic protein-2 (BMP-2). Bone marrow stromal cells (BMSCs) cultured in a combination of BMP-2 and 2-N,6-O-sulfated chitosan (SCS) group exhibited a higher cell viability and sprouting ability. The cells also secreted more VEGF and NO. The expression patterns of angiogenic and osteogenic genes were analyzed, and VEGFR2 signaling was found to play a role in the enhancing effect of SCS. The chick embryo chorioallantoic membrane (CAM) assay revealed an enhanced angiogenic effect of BMP-2 when SCS was involved. In addition, we investigated angiogenesis and osteogenesis in mouse using a BMP-2-induced ectopic bone model. Histological and immune-staining analysis revealed that both bone and vascular tissue were enhanced when SCS was added. These data prove that SCS can improve the angiogenic potential of BMP-2 and thus lead to better bone regeneration.

中文翻译：

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2- N，6- O-硫酸化壳聚糖增强BMP-2介导的血管生成和成骨作用

硫酸化多糖是有吸引力的半合成材料，可用作模仿硫酸乙酰肝素来调节蛋白质活性和其他生理过程。在这项研究中，我们采用硫酸化壳聚糖来增强骨形态发生蛋白2（BMP-2）的血管生成能力。在BMP-2和2- N，6- O的组合中培养的骨髓基质细胞（BMSC）硫酸壳聚糖（SCS）组表现出更高的细胞活力和发芽能力。细胞还分泌更多的VEGF和NO。分析了血管生成和成骨基因的表达模式，发现VEGFR2信号在SCS的增强作用中起作用。小鸡胚胎绒膜尿囊膜（CAM）分析显示，当涉及SCS时，BMP-2的血管生成作用增强。此外，我们使用BMP-2诱导的异位骨模型研究了小鼠的血管生成和成骨作用。组织学和免疫染色分析表明，添加SCS后，骨骼和血管组织均得到增强。这些数据证明，SCS可以改善BMP-2的血管生成潜能，从而导致更好的骨骼再生。