Wisdom Cate, VanOosten Sarah Kay, Boone Kyle W, Khvostenko Dmytro, Arnold Paul M, Snead Malcolm L, Tamerler Candan
Bioengineering Program, University of Kansas, 3135A Learned Hall, 1530 W 15th Street Lawrence, Kansas 66045, USA.
Bioengineering Research Center (BERC), University of Kansas, 3138 Learned Hall, 1530 W 15th Street Lawrence, Kansas 66045, USA,
J Mol Eng Mater. 2016 Mar;4(1). doi: 10.1142/S2251237316400050. Epub 2016 Aug 22.
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 and , 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 . Surfaces coated with the chimeric peptide reduced dramatically the number of bacteria, with up to a nine-fold reduction for and a 48-fold reduction for 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.
手术部位感染是术后发病的常见原因，常常导致植入物松动，最终需要进行翻修手术，增加成本并导致更差的手术结果。由于植入物失效始于植入物表面，因此创建和控制生物材料界面在减少感染的同时改善宿主细胞与植入物的相互作用方面将发挥关键作用。在此，我们基于一种嵌合肽设计了一种仿生界面，该嵌合肽将钛结合肽（TiBP）与抗菌肽（AMP）整合到单个分子中，以直接结合到植入物表面，并对与临床植入物感染相关的两种细菌——[此处原文缺失细菌名称]和[此处原文缺失细菌名称]产生抗菌活性。为了优化抗菌活性，我们研究了分隔嵌合肽两个功能域的间隔域的设计。延长间隔域并改变其氨基酸组成，使对[此处原文缺失细菌名称]的最低抑菌浓度提高了三倍。涂有嵌合肽的表面显著减少了细菌数量，对[此处原文缺失细菌名称]最多减少了九倍，对[此处原文缺失细菌名称]最多减少了48倍，基于结构特征的抗菌活性预测得到了证实。与未处理的植入物表面相比，仿生界面处的宿主细胞附着和活力也得到了改善。用这种嵌合肽形成的仿生界面通过将抗菌作用与改善的宿主细胞对可植入钛材料的反应相结合，提供了无限的潜力，并且这种基于肽的方法可以扩展到各种生物材料表面。
