Department of Biomedical Engineering, Georgia Institute of Technology/Emory University, Atlanta, Georgia 30332, USA.
J Biomed Mater Res A. 2013 Jul;101(7):1915-25. doi: 10.1002/jbm.a.34484. Epub 2012 Dec 5.
Recombinant, elastin-like protein (ELP) polymers are of significant interest for the engineering of compliant, resilient soft tissues due to a wide range of tunable mechanical properties, biostability, and biocompatibility. Here, we enhance endothelial cell (EC) and mesenchymal stem cell compatibility with ELP constructs by addition of fibronectin (Fn) to the surface or bulk of ELP hydrogels. We find that cell adhesion, proliferation, and migration can be modulated by Fn addition. Adsorption of Fn to the hydrogel surface is more efficient than bulk blending. Surface immobilization of Fn by genipin crosslinking leads to stability without loss of bioactivity. Gels of varying mechanical modulus do not alter cell adhesion, proliferation, and migration in the range we investigate. However, more compliant gels promote an EC morphology suggesting tubulogenesis or network formation, whereas stiffer gels promote cobblestone morphology. Multilayer structures consisting of thin ELP sheets reinforced with collagen microfiber are fabricated and laminated through the culture of MSCs at layer interfaces. High cell viability in the resulting three-dimensional constructs suggests the applicability of Fn to the design of strong, resilient artificial blood vessels and other soft tissue replacements.
重组弹性蛋白样蛋白（ELP）聚合物由于其广泛的可调机械性能、生物稳定性和生物相容性，对于可延展、有弹性的软组织的工程设计具有重要意义。在这里，我们通过在 ELP 水凝胶的表面或本体中添加纤维连接蛋白（Fn）来提高内皮细胞（EC）和间充质干细胞与 ELP 构建体的相容性。我们发现，Fn 的添加可以调节细胞的黏附、增殖和迁移。Fn 吸附到水凝胶表面比本体混合更有效。通过京尼平交联将 Fn 固定在表面上可以保持其稳定性而不损失生物活性。我们研究的范围内，不同机械模量的凝胶不会改变细胞的黏附、增殖和迁移。然而，更柔软的凝胶促进 EC 形态形成管状或网络状，而较硬的凝胶促进鹅卵石状形态。通过在层间培养间充质干细胞，制造并层压由薄的 ELP 片和胶原微纤维增强的多层结构。在三维结构中，细胞具有很高的活力，这表明 Fn 可用于设计强韧、有弹性的人工血管和其他软组织替代品。
