Laboratory for Biomaterials and Bioengineering, Canada Research Chair I in Biomaterials and Bioengineering for the Innovation in Surgery, Department of Min-Met-Materials Engineering, Research Center of CHU de Quebec, Division of Regenerative Medicine, Laval University, Quebec City, QC G1V 0A6, Canada.
Canada Research Chair I in Cell-Matrix Biology, Faculty of Medicine, Department of Anatomy and Cell Biology, and Faculty of Dentistry McGill University, Montreal, QC H3A 0C7, Canada.
Biomaterials. 2018 Oct;180:130-142. doi: 10.1016/j.biomaterials.2018.07.013. Epub 2018 Jul 12.
One of the tightest bottlenecks in vascular tissue engineering (vTE) is the lack of strength and elasticity of engineered vascular wall models caused by limited elastic fiber deposition. In this study, flat and tubular collagen gel-based scaffolds were cellularised with vascular smooth muscle cells (SMCs) and supplemented with human plasma fibronectin (FN), a known master organizer of several extracellular matrix (ECM) fiber systems. The consequences of FN on construct maturation was investigated in terms of geometrical contraction, viscoelastic mechanical properties and deposition of core elastic fiber proteins. FN was retained in the constructs and promoted deposition of elastin by SMCs as well as of several proteins required for elastogenesis such as fibrillin-1, lysyl oxidase, fibulin-4 and latent TGF-β binding protein-4. Notably, gel contraction, tensile equilibrium elastic modulus and elasticity were strongly improved in tubular engineered tissues, approaching the behaviour of native arteries. In conclusion, this study demonstrates that FN exerts pivotal roles in directing SMC-mediated remodeling of scaffolds toward the production of a physiological-like, elastin-containing ECM with excellent mechanical properties. The developed FN-supplemented systems are promising for tissue engineering applications where the generation of mature elastic tissue is desired and represent valuable advanced in vitro models to investigate elastogenesis.
血管组织工程（vTE）中最紧迫的瓶颈之一是由于弹性纤维沉积有限，导致工程化血管壁模型的强度和弹性不足。在这项研究中，采用平滑肌细胞（SMCs）对基于胶原凝胶的平板和管状支架进行细胞化，并补充人血浆纤维连接蛋白（FN），FN 是几种细胞外基质（ECM）纤维系统的已知主要组织者。从几何收缩、粘弹性力学性能和核心弹性纤维蛋白沉积的角度，研究了 FN 对构建体成熟的影响。FN 保留在构建体中，促进 SMCs 沉积弹性蛋白以及弹性蛋白生成所需的几种蛋白，如原纤维蛋白 1、赖氨酰氧化酶、纤维连接蛋白 4 和潜伏 TGF-β 结合蛋白 4。值得注意的是，管状工程组织的凝胶收缩、拉伸平衡弹性模量和弹性显著提高，接近天然动脉的行为。总之，这项研究表明 FN 在指导 SMC 介导的支架重塑以产生具有优良机械性能的生理性含弹性蛋白 ECM 方面发挥着关键作用。开发的 FN 补充系统有望用于组织工程应用，其中需要生成成熟的弹性组织，并且代表了研究弹性蛋白生成的有价值的体外模型。
