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通过使用生物安全的三步反应固定碱性成纤维细胞生长因子,加速组织与多孔材料的整合。

Accelerated tissue integration into porous materials by immobilizing basic fibroblast growth factor using a biologically safe three-step reaction.

作者信息

Kakinoki Sachiro, Sakai Yusuke, Fujisato Toshia, Yamaoka Tetsuji

机构信息

Department of Biomedical Engineering, National Cerebral and Cardiovascular Center Research Institute, 5-7-1 Fujishiro-Dai, Suita, Osaka, 565-8565, Japan.

Department of Biomedical Engineering, Graduate School of Engineering, Osaka Institute of Technology, 5-16-1 Omiya, Asahi-Ku, Osaka, 535-8585, Japan.

出版信息

J Biomed Mater Res A. 2015 Dec;103(12):3790-7. doi: 10.1002/jbm.a.35516. Epub 2015 Jun 29.

Abstract

Soft tissue integration into a porous structure is important to prevent bacterial infection of percutaneous devices and improve tissue regeneration using porous scaffolds. Here, basic fibroblast growth factor (bFGF) was immobilized on porous polymer materials using a mild and biologically safe three-step reaction: (1) modification with a novel surface-modification peptide (penta-lysine-mussel adhesive sequence, which reacts with various matrices), (2) electrostatic binding of heparin with introduced penta-lysine, and (3) biologically specific binding of bFGF to heparin. Porous polyethylene specimens (PPSs) (D = 6.0 mm, H = 2.0 mm) with a good size for tissue integration were selected as a base material, immobilized with bFGF, and subcutaneously implanted into mice. Half of the unmodified PPSs extruded out of the body on day 112 postimplantation; however, the three-step reaction completely prevented sample rejection. Tissue integration was greatly accelerated by immobilizing bFGF. Direct physical coating of bFGF on PPS resulted in greater immobilization but lesser tissue integration than that after the three-step bFGF immobilization, indicating that heparin binds and enhances bFGF efficacy. This three-step bFGF immobilization reaction will be applicable to various polymeric, metallic, and ceramic materials and is a simple strategy to integrate tissue on porous medical devices or scaffolds for tissue regeneration.

摘要

软组织与多孔结构的整合对于预防经皮设备的细菌感染以及利用多孔支架促进组织再生非常重要。在此,使用温和且生物安全的三步反应将碱性成纤维细胞生长因子(bFGF)固定在多孔聚合物材料上:(1)用一种新型表面修饰肽(五赖氨酸-贻贝粘附序列,可与各种基质反应)进行修饰,(2)肝素与引入的五赖氨酸进行静电结合,以及(3)bFGF与肝素的生物特异性结合。选择尺寸适合组织整合的多孔聚乙烯标本(PPSs)(直径 = 6.0 毫米,高度 = 2.0 毫米)作为基材,固定bFGF后皮下植入小鼠体内。未修饰的PPSs中有一半在植入后第112天从体内挤出;然而,三步反应完全防止了样本排斥。固定bFGF极大地加速了组织整合。将bFGF直接物理包被在PPS上导致的固定量更大,但组织整合程度低于三步固定bFGF后的情况,这表明肝素结合并增强了bFGF的功效。这种三步bFGF固定反应将适用于各种聚合物、金属和陶瓷材料,是一种在多孔医疗设备或组织再生支架上整合组织的简单策略。

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