Bush K A, Driscoll P F, Soto E R, Lambert C R, McGimpsey W G, Pins G D
Department of Biomedical Engineering, Worcester Polytechnic Institute, Worcester, Massachusetts, USA.
J Biomed Mater Res A. 2009 Sep 15;90(4):999-1009. doi: 10.1002/jbm.a.32168.
Precisely engineering the surface chemistry of biomaterials to modulate the adsorption and functionality of biochemical signaling molecules that direct cellular functions is critical in the development of tissue engineered scaffolds. Specifically, this study describes the use of functionalized self-assembled monolayers (SAMs) as a model system to assess the effects of biomaterial surface properties on controlling fibronectin (FN) conformation and concentration as well as keratinocyte function. By systematically analyzing FN adsorption at low and saturated surface densities, we distinguished between SAM-dependent effects of FN concentration and conformation on presenting cellular binding domains that direct cellular functions. Quantitative image analyses of immunostained samples showed that modulating the availability of the FN synergy site directly correlated with changes in keratinocyte attachment, spreading, and differentiation, through integrin-mediated signaling mechanisms. The results of this study will be used to elucidate design features that can be incorporated into dermal equivalents and percutaneous implants to enhance the rate of re-epithelialization and tissue regeneration. Furthermore, these findings indicate that SAM-based model systems are a valuable tool for designing and investigating the development of scaffolds that regulate the conformation of extracellular matrix cues and cellular functions that accelerate the rate of tissue regeneration.
精确设计生物材料的表面化学性质,以调节指导细胞功能的生化信号分子的吸附和功能,这在组织工程支架的开发中至关重要。具体而言,本研究描述了使用功能化自组装单分子层(SAMs)作为模型系统,以评估生物材料表面性质对控制纤连蛋白(FN)构象和浓度以及角质形成细胞功能的影响。通过系统分析低表面密度和饱和表面密度下的FN吸附情况,我们区分了FN浓度和构象对呈现指导细胞功能的细胞结合域的SAM依赖性效应。免疫染色样本的定量图像分析表明,通过整合素介导的信号传导机制,调节FN协同位点的可用性与角质形成细胞的附着、铺展和分化变化直接相关。本研究结果将用于阐明可纳入真皮替代物和经皮植入物的设计特征,以提高再上皮化和组织再生的速率。此外,这些发现表明,基于SAM的模型系统是设计和研究调节细胞外基质线索构象和加速组织再生速率的细胞功能的支架开发的有价值工具。