Polyglutamate directed coupling of bioactive peptides for the delivery of osteoinductive signals on allograft bone.
Polyglutamate directed coupling of bioactive peptides for the delivery of osteoinductive signals on allograft bone.
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DOI：
10.1016/j.biomaterials.2012.10.046
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发表时间：
2013-02
期刊：
影响因子：
14
通讯作者：
Bellis, Susan L.
中科院分区：
文献类型：
--
作者：
Culpepper, Bonnie K.;Bonvallet, Paul P.;Reddy, Michael S.;Ponnazhagan, Selvarangan;Bellis, Susan L.
同种异体移植骨通常用作自体移植骨的替代品，但同种异体移植骨由于加工而缺乏自体骨中存在的许多骨诱导因子。在这项研究中，我们研究了一种用骨再生因子重建同种异体移植物的方法。具体来说，来自 I 型胶原蛋白的骨诱导肽 DGEA 被设计为表达七谷氨酸 (E7) 结构域，该结构域与骨矿物质内的羟基磷灰石结合。将 E7 添加到 DGEA 中，同种异体移植物上的肽负载量增加了 9 倍，并且经过 5 天的间隔并进行大量清洗后，保留率显着提高。当考虑到更大的初始负载和保留时，E7 结构域使同种异体移植物表面的肽密度增加了 45 倍。肽包被的同种异体移植物也被皮下植入大鼠体内，发现E7DGEA在体内保留至少3个月。有趣的是，静脉注射的 E7DGEA 肽在骨组织内积聚，这表明 E7 结构域在药物递送至骨中的潜在作用。最后，我们确定，与 DGEA 一样，E7 修饰增强了生物活性 BMP2 衍生肽在同种异体移植物上的偶联。这些结果表明，E7 结构域可用于将多种类型的骨再生分子偶联到同种异体移植物的表面，以重新引入骨诱导信号，并有可能推进同种异体移植物的治疗。
Allograft bone is commonly used as an alternative to autograft, however allograft lacks many osteoinductive factors present in autologous bone due to processing. In this study, we investigated a method to reconstitute allograft with osteoregenerative factors. Specifically, an osteoinductive peptide from collagen I, DGEA, was engineered to express a heptaglutamate (E7) domain, which binds the hydroxyapatite within bone mineral. Addition of E7 to DGEA resulted in 9× greater peptide loading on allograft, and significantly greater retention after a 5-day interval with extensive washing. When factoring together greater initial loading and retention, the E7 domain directed a 45-fold enhancement of peptide density on the allograft surface. Peptide-coated allograft was also implanted subcutaneously into rats and it was found that E7DGEA was retained in vivo for at least 3 months. Interestingly, E7DGEA peptides injected intravenously accumulated within bone tissue, implicating a potential role for E7 domains in drug delivery to bone. Finally, we determined that, as with DGEA, the E7 modification enhanced coupling of a bioactive BMP2-derived peptide on allograft. These results suggest that E7 domains are useful for coupling many types of bone-regenerative molecules to the surface of allograft to reintroduce osteoinductive signals and potentially advance allograft treatments.
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影响因子：
3.7
作者：
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