Harrington Daniel A, Cheng Earl Y, Guler Mustafa O, Lee Leslie K, Donovan Jena L, Claussen Randal C, Stupp Samuel I
Department of Materials Science and Engineering, Northwestern University, Evanston, Illinois 60208, and Division of Pediatric Urology, Children's Memorial Hospital, Chicago 60614, USA.
J Biomed Mater Res A. 2006 Jul;78(1):157-67. doi: 10.1002/jbm.a.30718.
An important challenge in regenerative medicine is the design of suitable bioactive scaffold materials that can act as artificial extracellular matrices. We reported previously on a family of peptide-amphiphile (PA) molecules that self-assemble into high-aspect ratio nanofibers under physiological conditions, and can display bioactive peptide epitopes along each nanofiber's periphery. One type of PA displays its epitope at a branched site using a lysine dendron, a molecular feature that improves epitope availability on the nanofiber surface. In this work, we describe the application of these branched PA (b-PA) systems as self-assembling coatings for fiber-bonded poly(glycolic acid) scaffolds. b-PAs bearing variations of the RGDS adhesion epitope from fibronectin were shown by elemental analysis to coat repeatably onto fiber scaffolds. The retention of supramolecular organization after coating on the scaffold was demonstrated through spectroscopic identification of beta-sheet structures and the close association of hydrophobic tails in a model pyrene-containing PA system. Primary human bladder smooth muscle cells demonstrated greater initial adhesion to b-PA-functionalized scaffolds than to bare scaffolds or to those coated with linear PAs. This strategy of molecular design and coating may have potential application in bladder tissue regeneration.
再生医学中的一个重要挑战是设计合适的生物活性支架材料，使其能够充当人工细胞外基质。我们之前报道过一类肽两亲分子（PA），它们在生理条件下自组装成高纵横比的纳米纤维，并且可以沿着每根纳米纤维的周边展示生物活性肽表位。一种PA利用赖氨酸树枝状分子在分支位点展示其表位，这一分子特征提高了纳米纤维表面表位的可及性。在这项工作中，我们描述了这些分支PA（b-PA）系统作为纤维粘结聚乙醇酸支架的自组装涂层的应用。通过元素分析表明，带有来自纤连蛋白的RGDS粘附表位变体的b-PA能够可重复地涂覆在纤维支架上。通过对β-折叠结构的光谱鉴定以及在含芘模型PA系统中疏水尾的紧密缔合，证明了在支架上涂层后超分子结构得以保留。原代人膀胱平滑肌细胞对b-PA功能化支架的初始粘附力比对裸支架或涂有线性PA的支架更强。这种分子设计和涂层策略可能在膀胱组织再生中具有潜在应用。
