Enhancement of peptide coupling to hydroxyapatite and implant osseointegration through collagen mimetic peptide modified with a polyglutamate domain.

Enhancement of peptide coupling to hydroxyapatite and implant osseointegration through collagen mimetic peptide modified with a polyglutamate domain.
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DOI:
10.1016/j.biomaterials.2010.08.020
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发表时间:
2010-12
期刊:
影响因子:
14
通讯作者:
Bellis, Susan L.
Bellis, Susan L.
中科院分区:
工程技术1区
文献类型:
--
作者:
Culpepper, Bonnie K.;Phipps, Matthew C.;Bonvallet, Paul P.;Bellis, Susan L.

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羟基磷灰石(HA)具有较高的骨传导性,是一种应用广泛的骨修复材料。然而,通过生物活性因子对表面进行功能化来改善HA性能的策略是有限的。在这项研究中,我们探索了使用透明质酸结合结构域(七谷氨酸,“E7”)来促进胶原模拟肽DGEA与两种类型的含HA材料的偶联,即固体HA圆盘和含有纳米HA的静电纺丝聚己内酯基质。我们发现,E7结构域在体外将更多的肽定向到HA表面,并增强了两种材料上的肽保留率。此外,E7修饰的多肽在体内至少保留了两个月,这突显了这一机制作为生物活性多肽的持续递送系统的潜力。最重要的是,与DGEA-HA相比,E7-DGEA偶联HA能促进间充质干细胞的黏附和成骨分化,并增加新骨形成和骨-种植体在植入大鼠胫骨内的HA盘上的直接接触。总之,这些结果支持使用E7-DGEA多肽在HA基质上促进成骨,并进一步表明E7结构域可以作为一种通用工具,将各种骨再生分子锚定到任何类型的含有HA的材料上。
Hydroxyapatite (HA) is a widely-used biomaterial for bone repair due to its high degree of osteoconductivity. However, strategies for improving HA performance by functionalizing surfaces with bioactive factors are limited. In this study, we explored the use of an HA-binding domain (heptaglutamate, “E7”) to facilitate coupling of the collagen mimetic peptide, DGEA, to two types of HA-containing materials, solid HA disks and electrospun polycaprolactone matrices incorporating nanoparticulate HA. We found that the E7 domain directed significantly more peptide to the surface of HA and enhanced peptide retention on both materials in vitro. Moreover, E7-modified peptides were retained in vivo for at least two months, highlighting the potential of this mechanism as a sustained delivery system for bioactive peptides. Most importantly, E7-DGEA-coupled HA, as compared with DGEA-HA, enhanced the adhesion and osteoblastic differentiation of mesenchymal stem cells, and also increased new bone formation and direct bone-implant contact on HA disks implanted into rat tibiae. Collectively, these results support the use of E7-DGEA peptides to promote osteogenesis on HA substrates, and further suggest that the E7 domain can serve as a universal tool for anchoring a wide variety of bone regenerative molecules to any type of HA-containing material.
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