Wang Allen Y, Foss Catherine A, Leong Shirley, Mo Xiao, Pomper Martin G, Yu Seungju M
Department of Materials Science and Engineering, The Johns Hopkins University, Baltimore, Maryland 21218, USA.
Biomacromolecules. 2008 Jul;9(7):1755-63. doi: 10.1021/bm701378k. Epub 2008 Jun 12.
Functionalized collagen that incorporates exogenous compounds may offer new and improved biomaterials applications, especially in drug-delivery, multifunctional implants, and tissue engineering. To that end, we developed a specific and reversible collagen modification technique utilizing associative chain interactions between synthetic collagen mimetic peptide (CMP) [(ProHypGly) chi; Hyp = hydroxyproline] and type I collagen. Here we show temperature-dependent collagen binding and subsequent release of a series of CMPs with varying chain lengths indicating a triple helical propensity driven binding mechanism. The binding took place when melted, single-strand CMPs were allowed to fold while in contact with reconstituted type I collagens. The binding affinity is highly specific to collagen as labeled CMP bound to nanometer scale periodic positions on type I collagen fibers and could be used to selectively image collagens in ex vivo human liver tissue. When heated to physiological temperature, bound CMPs discharged from the collagen at a sustained rate that correlated with CMP's triple helical propensity, suggesting that sustainability is mediated by dynamic collagen-CMP interactions. We also report on the spatially defined modification of collagen film with linear and multi-arm poly(ethylene glycol)-CMP conjugates; at 37 degrees C, these PEG-CMP conjugates exhibited temporary cell repelling activity lasting up to 9 days. These results demonstrate new opportunities for targeting pathologic collagens for diagnostic or therapeutic applications and for fabricating multifunctional collagen coatings and scaffolds that can temporally and spatially control the behavior of cells associated with the collagen matrices.
结合外源性化合物的功能化胶原蛋白可能会带来新的、改进的生物材料应用，特别是在药物递送、多功能植入物和组织工程方面。为此，我们开发了一种特定的、可逆的胶原蛋白修饰技术，该技术利用合成胶原蛋白模拟肽（CMP）[（ProHypGly）χ；Hyp = 羟脯氨酸]与I型胶原蛋白之间的缔合链相互作用。在这里，我们展示了温度依赖性的胶原蛋白结合以及一系列不同链长的CMP的后续释放，这表明了一种由三螺旋倾向驱动的结合机制。当融化的单链CMP与重组的I型胶原蛋白接触时允许其折叠，结合就会发生。结合亲和力对胶原蛋白具有高度特异性，因为标记的CMP结合到I型胶原纤维上的纳米级周期性位置，并且可用于在体外人肝组织中选择性地成像胶原蛋白。当加热到生理温度时，结合的CMP以与CMP的三螺旋倾向相关的持续速率从胶原蛋白中释放出来，这表明可持续性是由动态的胶原蛋白-CMP相互作用介导的。我们还报道了用线性和多臂聚乙二醇-CMP缀合物对胶原膜进行空间定义的修饰；在37摄氏度时，这些PEG-CMP缀合物表现出持续长达9天的临时细胞排斥活性。这些结果为靶向病理性胶原蛋白用于诊断或治疗应用以及制造能够在时间和空间上控制与胶原基质相关细胞行为的多功能胶原涂层和支架提供了新的机会。
