Li Xian, Contreras-Garcia Angel, LoVetri Karen, Yakandawala Nandadeva, Wertheimer Michael R, De Crescenzo Gregory, Hoemann Caroline D
Department of Chemical Engineering, École Polytechnique, Montréal, Quebec, Canada, H3C 3A7.
Biomedical Sciences and Technology Research Group/Groupe de Recherche Sciences et Technologies Biomedicales (GRSTB), École Polytechnique, Montréal, Quebec, Canada, H3C 3A7.
J Biomed Mater Res A. 2015 Dec;103(12):3736-46. doi: 10.1002/jbm.a.35511. Epub 2015 Jun 11.
In the context of porous bone void filler for oral bone reconstruction, peptides that suppress microbial growth and promote osteoblast function could be used to enhance the performance of a porous bone void filler. We tested the hypothesis that P15-CSP, a novel fusion peptide containing collagen-mimetic osteogenic peptide P15, and competence-stimulating peptide (CSP), a cationic antimicrobial peptide, has emerging properties not shared by P15 or CSP alone. Peptide-coated surfaces were tested for antimicrobial activity toward Streptoccocus mutans, and their ability to promote human mesenchymal stem cell (MSC) attachment, spreading, metabolism, and osteogenesis. In the osteogenesis assay, peptides were coated on tissue culture plastic and on thin films generated by plasma-enhanced chemical vapor deposition to have hydrophilic or hydrophobic character (water contact angles 63°, 42°, and 92°, respectively). S. mutans planktonic growth was specifically inhibited by CSP, whereas biofilm formation was inhibited by P15-CSP. MSC adhesion and actin stress fiber formation was strongly enhanced by CSP, P15-CSP, and fibronectin coatings and modestly enhanced by P15 versus uncoated surfaces. Metabolic assays revealed that CSP was slightly cytotoxic to MSCs. MSCs developed alkaline phosphatase activity on all surfaces, with or without peptide coatings, and consistently deposited the most biomineralized matrix on hydrophilic surfaces coated with P15-CSP. Hydrophobic thin films completely suppressed MSC biomineralization, consistent with previous findings of suppressed osteogenesis on hydrophobic bioplastics. Collective data in this study provide new evidence that P15-CSP has unique dual capacity to suppress biofilm formation, and to enhance osteogenic activity as a coating on hydrophilic surfaces.
在用于口腔骨重建的多孔骨缺损填充材料的背景下,能够抑制微生物生长并促进成骨细胞功能的肽可用于增强多孔骨缺损填充材料的性能。我们验证了以下假设:P15-CSP,一种含有模拟胶原蛋白的成骨肽P15和具有抗菌活性的阳离子肽—— competence-stimulating peptide(CSP)的新型融合肽,具有单独的P15或CSP所不具备的新特性。对肽包被的表面进行了针对变形链球菌的抗菌活性测试,以及它们促进人间充质干细胞(MSC)附着、铺展、代谢和成骨的能力测试。在成骨试验中,将肽包被在组织培养塑料以及通过等离子体增强化学气相沉积生成的具有亲水性或疏水性特征(水接触角分别为63°、42°和92°)的薄膜上。CSP特异性抑制变形链球菌的浮游生长,而P15-CSP抑制生物膜形成。CSP、P15-CSP和纤连蛋白包被显著增强了MSC的黏附以及肌动蛋白应力纤维的形成,与未包被的表面相比,P15也适度增强了这种作用。代谢试验表明,CSP对MSC有轻微的细胞毒性。无论有无肽包被,MSC在所有表面上均产生碱性磷酸酶活性,并且在涂有P15-CSP的亲水性表面上始终沉积最多的生物矿化基质。疏水性薄膜完全抑制了MSC的生物矿化,这与先前在疏水性生物塑料上抑制成骨的研究结果一致。本研究中的综合数据提供了新的证据,即P15-CSP具有独特的双重能力,可抑制生物膜形成,并作为亲水性表面的涂层增强成骨活性。