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构建肝素修饰的胰腺脱细胞支架以改善其再内皮化。

Constructing heparin-modified pancreatic decellularized scaffold to improve its re-endothelialization.

作者信息

Xu Liancheng, Guo Yibing, Huang Yan, Xiong Yicheng, Xu Yang, Li Xiaohong, Lu Jingjing, Wang Lei, Wang Yao, Lu Yuhua, Wang Zhiwei

机构信息

1 Research center of clinical medical, Affiliated Hospital of Nantong University, Nantong City, Jiangsu, PR China.

2 Department of General Surgery, Affiliated Hospital of Nantong University, Nantong City, Jiangsu, PR China.

出版信息

J Biomater Appl. 2018 Mar;32(8):1063-1070. doi: 10.1177/0885328217752859. Epub 2018 Jan 16.

Abstract

Pancreas transplantation is considered as a promising therapeutic option with the potential to cure diabetes. However, efficacy of current clinical transplantation is limited by the donor organ. With regard to creating a functional pancreas-tissue equivalent for transplantation, vascularization remains a large obstacle. To enhance the angiogenic properties of pancreatic decellularized scaffold, surface modification of the vasculature was used to promote endothelialization efficiency. In this study, an endothelialized pancreatic decellularized scaffold was obtained through heparin modification under mild conditions. The immobilization of heparin was performed through 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide and N-Hydroxysuccinimide. The morphology, ultra-structure and porosity of the heparinized scaffold were characterized by toluidine blue staining, scanning electron microscope and infrared spectrum. The adhesion, proliferation and angiogenesis of human umbilical vein endothelial cells on heparin-pancreatic decellularized scaffold were also researched in vitro. In vivo transplantation was also performed to observe the location of human umbilical vein endothelial cells and the formation of new blood vessel, which exhibited significant differences with pancreatic decellularized scaffold group (p<0.05). These findings indicated that the endothelialized heparin-pancreatic decellularized scaffold may be used to solve the problem of blood supply and to support the function of insulin-secreting cells better after in vivo transplantation, and therefore, would be a potential candidate for pancreatic tissue engineering.

摘要

胰腺移植被认为是一种有前景的治疗选择,有治愈糖尿病的潜力。然而,目前临床移植的疗效受到供体器官的限制。关于创建用于移植的功能性胰腺组织替代物,血管化仍然是一个巨大的障碍。为了增强胰腺脱细胞支架的血管生成特性,采用对脉管系统进行表面修饰的方法来提高内皮化效率。在本研究中,通过在温和条件下进行肝素修饰获得了内皮化的胰腺脱细胞支架。肝素的固定通过1-乙基-3-(3-二甲基氨基丙基)-碳二亚胺和N-羟基琥珀酰亚胺来进行。用甲苯胺蓝染色、扫描电子显微镜和红外光谱对肝素化支架的形态、超微结构和孔隙率进行了表征。还在体外研究了人脐静脉内皮细胞在肝素化胰腺脱细胞支架上的黏附、增殖和血管生成情况。也进行了体内移植以观察人脐静脉内皮细胞的定位和新血管的形成,其与胰腺脱细胞支架组相比有显著差异(p<0.05)。这些发现表明,内皮化的肝素化胰腺脱细胞支架可用于解决血液供应问题,并在体内移植后更好地支持胰岛素分泌细胞的功能,因此,将是胰腺组织工程的一个潜在候选物。

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