Browning Mary Beth, Guiza Viviana, Russell Brooke, Rivera Jose, Cereceres Stacy, Höök Magnus, Hahn Mariah S, Cosgriff-Hernandez Elizabeth M
1 Department of Biomedical Engineering, Texas A&M University , College Station, Texas.
Tissue Eng Part A. 2014 Dec;20(23-24):3130-41. doi: 10.1089/ten.TEA.2013.0602.
The highly tunable biological, chemical, and physical properties of bioactive hydrogels enable their use in an array of tissue engineering and drug delivery applications. Systematic modulation of these properties can be used to elucidate key cell-material interactions to improve therapeutic effects. For example, the rate and extent of endothelialization are critical to the long-term success of many blood-contacting devices. To this end, we have developed a bioactive hydrogel that could be used as coating on cardiovascular devices to enhance endothelial cell (EC) adhesion and migration. The current work investigates the relative impact of hydrogel variables on key endothelialization processes. The bioactive hydrogel is based on poly(ethylene glycol) (PEG) and a streptococcal collagen-like (Scl2-2) protein that has been modified with integrin α1β1 and α2β1 binding sites. The use of PEG hydrogels allows for incorporation of specific bioactive cues and independent manipulation of scaffold properties. The selective integrin binding of Scl2-2 was compared to more traditional collagen-modified PEG hydrogels to determine the effect of integrin binding on cell behavior. Protein functionalization density, protein concentration, and substrate modulus were independently tuned with both Scl2-2 and collagen to determine the effect of each variable on EC adhesion, spreading, and migration. The findings here demonstrate that increasing substrate modulus, decreasing functionalization density, and increasing protein concentration can be utilized to increase EC adhesion and migration. Additionally, PEG-Scl2-2 hydrogels had higher migration speeds and proliferation over 1 week compared with PEG-collagen gels, demonstrating that selective integrin binding can be used to enhance cell-material interactions. Overall, these studies contribute to the understanding of the effects of matrix cues on EC interactions and demonstrate the strong potential of PEG-Scl2-2 hydrogels to promote endothelialization of blood-contacting devices.
生物活性水凝胶具有高度可调节的生物学、化学和物理性质，使其能够用于一系列组织工程和药物递送应用中。对这些性质进行系统调节可用于阐明关键的细胞-材料相互作用，以提高治疗效果。例如，内皮化的速率和程度对许多血液接触装置的长期成功至关重要。为此，我们开发了一种生物活性水凝胶，可用于心血管装置的涂层，以增强内皮细胞（EC）的粘附和迁移。当前的工作研究了水凝胶变量对关键内皮化过程的相对影响。这种生物活性水凝胶基于聚乙二醇（PEG）和一种链球菌胶原样（Scl2-2）蛋白，该蛋白已用整合素α1β1和α2β1结合位点进行了修饰。PEG水凝胶的使用允许掺入特定的生物活性线索，并独立操纵支架性质。将Scl2-2的选择性整合素结合与更传统的胶原修饰的PEG水凝胶进行比较，以确定整合素结合对细胞行为的影响。用Scl2-2和胶原独立调节蛋白质功能化密度、蛋白质浓度和底物模量，以确定每个变量对EC粘附、铺展和迁移的影响。此处的研究结果表明，增加底物模量、降低功能化密度和增加蛋白质浓度可用于增加EC的粘附和迁移。此外，与PEG-胶原凝胶相比，PEG-Scl2-2水凝胶在1周内具有更高的迁移速度和增殖能力，表明选择性整合素结合可用于增强细胞-材料相互作用。总体而言，这些研究有助于理解基质线索对EC相互作用的影响，并证明了PEG-Scl2-2水凝胶在促进血液接触装置内皮化方面的强大潜力。
