Copper ions-photo dual-crosslinked alginate hydrogel for angiogenesis and osteogenesis.

Guochen Liu, Shanshan Ye, Yue Li, Jing Yang, Simin Wang, Yuan Liu, Sisi Yang, Yinping Tian, Miao Yin, Bo Cheng
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Abstract

Early healing of bone defects is still a clinical challenge. Many bone-filling materials have been studied, among which photocrosslinked alginate has received significant attention due to its good biocompatibility and morphological plasticity. Although it has been confirmed that photocrosslinked alginate can be used as an extracellular matrix for 3D cell culture, it lacks osteogenesis-related biological functions. This study constructed a copper ions-photo dual-crosslinked alginate hydrogel scaffold by controlling the copper ion concentration. The scaffolds were shaped by photocrosslinking and then endowed with biological functions by copper ions crosslinking. According to in vitro research, the dual-crosslinked hydrogel increased the compressive strength and favored copper dose-dependent osteoblast differentiation and cell surface adherence of rat bone marrow mesenchymal stem cells and the expression of type I collagen (Col1), runt-related transcription factor 2 (Runx2), osteocalcin (OCN), vascular endothelial growth factor (VEGF). In addition, hydrogel scaffolds were implanted into rat skull defects, and more angiogenesis and osteogenesis could be observed in in vivo studies. The above results show that the copper-photo-crosslinked hydrogel scaffold has excellent osseointegration properties and can potentially promote angiogenesis and early healing of bone defects, providing a reference solution for bone tissue engineering materials.

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用于血管生成和骨生成的铜离子-照片双交联藻酸盐水凝胶。
骨缺损的早期愈合仍然是一项临床挑战。人们对许多骨填充材料进行了研究,其中光交联藻酸盐因其良好的生物相容性和形态可塑性而备受关注。虽然已证实光交联藻酸盐可用作三维细胞培养的细胞外基质,但它缺乏成骨相关的生物学功能。本研究通过控制铜离子浓度,构建了铜离子-光电双交联藻酸盐水凝胶支架。该支架通过光交联成型,然后通过铜离子交联赋予其生物功能。体外研究表明,双交联水凝胶增加了抗压强度,有利于铜剂量依赖性的成骨细胞分化和大鼠骨髓间充质干细胞的细胞表面粘附,以及 I 型胶原(Col1)、Runt 相关转录因子 2(Runx2)、骨钙素(OCN)、血管内皮生长因子(VEGF)的表达。此外,将水凝胶支架植入大鼠颅骨缺损处,在体内研究中可以观察到更多的血管生成和骨生成。上述结果表明,铜-光交联水凝胶支架具有良好的骨结合性能,可促进血管生成和骨缺损的早期愈合,为骨组织工程材料提供了参考方案。
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