Controlling the Biomimetic Implant Interface: Modulating Antimicrobial Activity by Spacer Design.
Controlling the Biomimetic Implant Interface: Modulating Antimicrobial Activity by Spacer Design.
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DOI：
10.1142/s2251237316400050
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发表时间：
2016-08
影响因子：
1.5
通讯作者：
Cate Wisdom;S. K. Vanoosten;Kyle Boone;D. Khvostenko;P. Arnold;M. Snead;C. Tamerler
中科院分区：
文献类型：
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作者：
Cate Wisdom;S. K. Vanoosten;Kyle Boone;D. Khvostenko;P. Arnold;M. Snead;C. Tamerler
手术部位感染是术后并发症的常见原因，通常会导致种植体松动，最终需要翻修手术，增加成本和更糟糕的手术结果。由于种植体失效始于种植体表面，创建和控制生物材料界面将在减少感染同时改善宿主细胞与种植体的相互作用方面发挥关键作用。在这里，我们设计了一个基于嵌合肽的仿生界面，该嵌合肽将钛结合肽(TiBP)和抗菌肽(AMP)结合到单个分子中，直接结合到种植体表面，并提供对变形链球菌和表皮葡萄球菌的抗菌活性，这两种细菌与临床种植体感染有关。为了优化抗菌活性，我们研究了分隔嵌合肽的两个功能结构域的间隔区的设计。延长和改变间隔区的氨基酸组成可使其对变形链球菌的最低抑菌浓度提高3倍。涂有嵌合肽的表面显著减少了细菌数量，变形链球菌的细菌数量减少了9倍，表皮葡萄球菌的细菌数量减少了48倍。基于结构特征的抗菌活性的从头算预测得到了证实。与未经处理的植入物表面相比，宿主细胞在仿生界面的附着和活性也得到了改善。用这种嵌合肽形成的仿生界面通过将抗菌和改善的宿主细胞反应偶联到可植入的钛材料上，提供了无限的潜力，这种基于多肽的方法可以扩展到各种生物材料表面。
Surgical site infection is a common cause of post-operative morbidity, often leading to implant loosening, ultimately requiring revision surgery, increased costs and worse surgical outcomes. Since implant failure starts at the implant surface, creating and controlling the bio-material interface will play a critical role in reducing infection while improving host cell-to-implant interaction. Here, we engineered a biomimetic interface based upon a chimeric peptide that incorporates a titanium binding peptide (TiBP) with an antimicrobial peptide (AMP) into a single molecule to direct binding to the implant surface and deliver an antimicrobial activity against S. mutans and S. epidermidis, two bacteria which are linked with clinical implant infections. To optimize antimicrobial activity, we investigated the design of the spacer domain separating the two functional domains of the chimeric peptide. Lengthening and changing the amino acid composition of the spacer resulted in an improvement of minimum inhibitory concentration by a three-fold against S. mutans. Surfaces coated with the chimeric peptide reduced dramatically the number of bacteria, with up to a nine-fold reduction for S. mutans and a 48-fold reduction for S. epidermidis. Ab initio predictions of antimicrobial activity based on structural features were confirmed. Host cell attachment and viability at the biomimetic interface were also improved compared to the untreated implant surface. Biomimetic interfaces formed with this chimeric peptide offer interminable potential by coupling antimicrobial and improved host cell responses to implantable titanium materials, and this peptide based approach can be extended to various biomaterials surfaces.