Polysaccharide-based biomaterials with on-demand nitric oxide releasing property regulated by enzyme catalysis
Polysaccharide-based biomaterials with on-demand nitric oxide releasing property regulated by enzyme catalysis
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具有酶催化调节的按需一氧化氮释放特性的多糖基生物材料
DOI：
10.1016/j.biomaterials.2013.07.045
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发表时间：
2013-11-01
期刊：
影响因子：
14
通讯作者：
Kong, Deling
中科院分区：
文献类型：
--
作者：
Zhao, Qiang;Zhang, Jimin;Kong, Deling
一氧化氮(NO)在细胞信号转导中的调节作用已被广泛认识。临床上，已知NO缺乏与严重的血管疾病有关，特别是在长期患有糖尿病的患者中。NO的外源性代偿是一种很有前途的治疗策略，尽管缺乏稳定的NO化合物往往会导致不满意的临床结果。在本研究中，我们报道了一种稳定的梳状聚合物(CS-NO)，它以糖基化的NO化合物为侧链，以壳聚糖(CS)为骨架，用于控制NO的释放。NO的按需释放是通过控制CS-NO聚合物的分解过程来实现的，CS-NO聚合物被半乳糖阻断，只有在糖苷酶存在的情况下才能发生，使NO的释放动力学与糖苷酶的浓度密切相关。此外，由于CS-NO聚合物的高度稳定性，还可以加工成支撑膜或可注射水凝胶，进一步展示了其临床潜力。事实上，我们报道了NO释放膜抑制血小板黏附，延长激活的部分凝血活酶时间(APTT)，如富含血小板血浆(PRP)检测所示。我们还观察到，体外培养的人脐静脉内皮细胞生长增强，而血管平滑肌细胞的增殖受到抑制。此外，体内给予CS-NO溶液显著促进了糖尿病小鼠后肢缺血的血管生成。观察CS-NO对肢体坏死的保护作用。鉴于一氧化氮的生理重要性，CS-NO聚合物可能被认为是治疗血管疾病和糖尿病足的有前途的选择。(C)2013爱思唯尔有限公司。保留所有权利。
The regulatory role of nitric oxide (NO) in cell signaling has been well recognized. Clinically, NO deficiency is known to be associated with severe vascular disorders, especially in patients with long-term diabetes. Exogenous compensation of NO is a promising therapeutic strategy, although the lack of stable NO compounds often lead to unsatisfactory clinical outcomes. In the present study, we report a stable comb-shaped polymer (CS-NO) using glycosylated NO compound as pendent chains and chitosan (CS) as backbone for controlled NO release. The on-demand release of NO is achieved by controlling the decomposition process of the CS-NO polymer, which is blocked by galactose and only occurs in the presence of glycosidase, making the NO releasing kinetic closely correlate with the glycosidase concentration. In addition, due to its high stability, the CS-NO polymers can also be processed into supportive membrane or injectable hydrogel, further demonstrating its clinical potential. Indeed, we report that the NO-releasing membrane inhibited platelet adhesion, prolonged activated partial thromboplastin time (APTT) as shown in the platelet-rich-plasma (PRP) assay. We also observe enhanced human umbilical vein endothelial cell growth yet suppressed vascular smooth muscle cell proliferation on the NO-contained membrane in vitro. Furthermore, in vivo administration of CS-NO solution significantly enhanced angiogenesis in diabetic mice with hind-limb ischemia. Protective effect of CS-NO was also observed against limb necrosis. Given the physiological importance of NO, the CS-NO polymer may be considered a promising option in therapeutic development against vascular disorders and diabetic feet. (C) 2013 Elsevier Ltd. All rights reserved.