Center for Advanced Biomaterials for Health Care@CRIB Istituto Italiano di Tecnologia, Largo Barsanti e Matteucci n. 53, I-80125 Napoli, Italy.
Biofabrication. 2016 Jan 29;8(1):015010. doi: 10.1088/1758-5090/8/1/015010.
The fabrication of functional tissue units is one of the major challenges in tissue engineering due to their in vitro use in tissue-on-chip systems, as well as in modular tissue engineering for the construction of macrotissue analogs. In this work, we aim to engineer dermal tissue micromodules obtained by culturing human dermal fibroblasts into porous gelatine microscaffold. We proved that such stromal cells coupled with gelatine microscaffolds are able to synthesize and to assemble an endogenous extracellular matrix (ECM) resulting in tissue micromodules, which evolve their biophysical features over the time. In particular, we found a time-dependent variation of oxygen consumption kinetic parameters, of newly formed ECM stiffness and of micromodules self-aggregation properties. As consequence when used as building blocks to fabricate larger tissues, the initial tissue micromodules state strongly affects the ECM organization and maturation in the final macrotissue. Such results highlight the role of the micromodules properties in controlling the formation of three-dimensional macrotissue in vitro, defining an innovative design criterion for selecting tissue-building blocks for modular tissue engineering.
功能组织单元的构建是组织工程学的主要挑战之一，因为它们在组织芯片系统中的体外应用，以及在用于构建大组织类似物的模块化组织工程学中都有应用。在这项工作中，我们旨在构建通过培养人真皮成纤维细胞到多孔明胶微支架中获得的皮肤组织微模块。我们证明，这种基质细胞与明胶微支架结合能够合成和组装内源性细胞外基质 (ECM)，从而形成组织微模块，这些微模块的生物物理特性会随着时间的推移而发生变化。具体来说，我们发现了氧消耗动力学参数、新形成的 ECM 硬度和微模块自聚集特性的时间依赖性变化。因此，当用作构建更大组织的构建块时，初始组织微模块的状态会强烈影响最终大组织中的 ECM 组织和成熟。这些结果强调了微模块特性在控制三维大组织体外形成中的作用，为模块化组织工程中选择组织构建块定义了一个创新的设计标准。
