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用于在生物材料上双重呈现生物活性肽基序的新型肽基平台。

Novel peptide-based platform for the dual presentation of biologically active peptide motifs on biomaterials.

作者信息

Mas-Moruno Carlos, Fraioli Roberta, Albericio Fernando, Manero José María, Gil F Javier

机构信息

Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Metallurgical Engineering, Technical University of Catalonia (UPC) , ETSEIB, Avenida Diagonal 647, 08028 Barcelona, Spain.

出版信息

ACS Appl Mater Interfaces. 2014 May 14;6(9):6525-36. doi: 10.1021/am5001213. Epub 2014 Apr 15.

DOI:10.1021/am5001213
PMID:24673628
Abstract

Biofunctionalization of metallic materials with cell adhesive molecules derived from the extracellular matrix is a feasible approach to improve cell-material interactions and enhance the biointegration of implant materials (e.g., osseointegration of bone implants). However, classical biomimetic strategies may prove insufficient to elicit complex and multiple biological signals required in the processes of tissue regeneration. Thus, newer strategies are focusing on installing multifunctionality on biomaterials. In this work, we introduce a novel peptide-based divalent platform with the capacity to simultaneously present distinct bioactive peptide motifs in a chemically controlled fashion. As a proof of concept, the integrin-binding sequences RGD and PHSRN were selected and introduced in the platform. The biofunctionalization of titanium with this platform showed a positive trend towards increased numbers of cell attachment, and statistically higher values of spreading and proliferation of osteoblast-like cells compared to control noncoated samples. Moreover, it displayed statistically comparable or improved cell responses compared to samples coated with the single peptides or with an equimolar mixture of the two motifs. Osteoblast-like cells produced higher levels of alkaline phosphatase on surfaces functionalized with the platform than on control titanium; however, these values were not statistically significant. This study demonstrates that these peptidic structures are versatile tools to convey multiple biofunctionality to biomaterials in a chemically defined manner.

摘要

用源自细胞外基质的细胞黏附分子对金属材料进行生物功能化修饰,是改善细胞与材料相互作用、增强植入材料生物整合性(如骨植入物的骨整合)的一种可行方法。然而,经典的仿生策略可能不足以引发组织再生过程中所需的复杂多样的生物信号。因此,新的策略聚焦于在生物材料上赋予多功能性。在本研究中,我们引入了一种新型的基于肽的二价平台,该平台能够以化学可控的方式同时呈现不同的生物活性肽基序。作为概念验证,选择整合素结合序列RGD和PHSRN并引入该平台。用此平台对钛进行生物功能化修饰后,与未涂层的对照样品相比,细胞附着数量呈增加趋势,成骨样细胞的铺展和增殖值在统计学上更高。此外,与用单一肽或两种基序的等摩尔混合物涂层的样品相比,它表现出统计学上相当或更好的细胞反应。在经该平台功能化修饰的表面上,成骨样细胞产生的碱性磷酸酶水平高于对照钛表面;然而,这些值在统计学上并不显著。本研究表明,这些肽结构是以化学定义的方式为生物材料传递多种生物功能的通用工具。

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