Fusion peptide engineered "statically-versatile" titanium implant simultaneously enhancing anti-infection, vascularization and osseointegration
Fusion peptide engineered "statically-versatile" titanium implant simultaneously enhancing anti-infection, vascularization and osseointegration
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DOI：
10.1016/j.biomaterials.2020.120446
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发表时间：
2021-01-01
期刊：
影响因子：
14
通讯作者：
Wang, Yingjun
中科院分区：
文献类型：
--
作者：
Chen, Junjian;Hu, Guansong;Wang, Yingjun
虽然抗菌钛种植体可以预防骨科中生物材料相关感染（BAI），但它们表现出细胞毒性和骨整合延迟。因此，多功能种植体是同时抑制BAI和促进骨整合的理想选择，特别是具有非必要外部刺激的“静态多功能”种植体，以促进应用。本研究通过硼氢化钠还原促进Cu(I)催化叠氮-炔环加成（CuAAC- sb）固定含有HHC36抗菌序列和QK血管生成序列的新型融合肽（FP），开发了一种“静态多用途”钛植入物，该方法比传统的抗坏血酸钠还原（CuAAC- sa）固定效率更高。经fp修饰的假体对金黄色葡萄球菌、大肠杆菌、铜绿假单胞菌和耐甲氧西林金黄色葡萄球菌等4种临床细菌的抑菌活性均达到96.8%以上，优于混合肽修饰的假体。这可以机械地归因于HHC36序列较大的细菌可达表面积。值得注意的是，植入物可以同时增强细胞增殖，上调HUVECs血管生成相关基因/蛋白（VEGF和VEGFR-2）和hBMSCs成骨相关基因/蛋白（ALP、COL-1、RUNX-2、OPN和OCN）的表达。在感染和非感染骨缺损模型的体内实验表明，fp工程种植体可以杀死99.63%的金黄色葡萄球菌，同时促进血管形成和骨整合。相信这项研究为发展“静态通用”骨科植入物提供了一个极好的策略。
Although antimicrobial titanium implants can prevent biomaterial-associated infection (BAI) in orthopedics, they display cytotoxicity and delayed osseointegration. Therefore, versatile implants are desirable for simultaneously inhibiting BAI and promoting osseointegration, especially "statically-versatile" ones with nonessential external stimulations for facilitating applications. Herein, we develop a "statically-versatile" titanium implant by immobilizing an innovative fusion peptide (FP) containing HHC36 antimicrobial sequence and QK angiogenic sequence via sodium borohydride reduction promoted Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC-SB), which shows higher immobilization efficiency than traditional CuAAC with sodium ascorbate reduction (CuAAC-SA). The FP-engineered implant exhibits over 96.8% antimicrobial activity against four types of clinical bacteria (S. aureus, E. coli, P. aeruginosa and methicillin-resistant S. aureus), being stronger than that modified with mixed peptides. This can be mechanistically attributed to the larger bacterial accessible surface area of HHC36 sequence. Notably, the implant can simultaneously enhance cellular proliferation, up-regulate expressions of angiogenesis-related genes/proteins (VEGF and VEGFR-2) of HUVECs and osteogenesis-related genes/proteins (ALP, COL-1, RUNX-2, OPN and OCN) of hBMSCs. In vivo assay with infection and non-infection bone-defect model reveals that the FP-engineered implant can kill 99.63% of S. aureus, and simultaneously promote vascularization and osseointegration. It is believed that this study presents an excellent strategy for developing "statically-versatile" orthopedic implants.