Trinity Centre for Bioengineering, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland; Department of Mechanical and Manufacturing Engineering, School of Engineering, Trinity College Dublin, Dublin, Ireland.
Trinity Centre for Bioengineering, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland; Department of Mechanical and Manufacturing Engineering, School of Engineering, Trinity College Dublin, Dublin, Ireland; Department of Anatomy, Royal College of Surgeons in Ireland, Dublin, Ireland; Advanced Materials and Bioengineering Research Centre (AMBER), Royal College of Surgeons in Ireland and Trinity College Dublin, Dublin, Ireland.
Biomaterials. 2019 Mar;197:194-206. doi: 10.1016/j.biomaterials.2018.12.028. Epub 2019 Jan 8.
Successful tissue engineering requires the generation of human scale implants that mimic the structure, composition and mechanical properties of native tissues. Here, we report a novel biofabrication strategy that enables the engineering of structurally organised tissues by guiding the growth of cellular spheroids within arrays of 3D printed polymeric microchambers. With the goal of engineering stratified articular cartilage, inkjet bioprinting was used to deposit defined numbers of mesenchymal stromal cells (MSCs) and chondrocytes into pre-printed microchambers. These jetted cell suspensions rapidly underwent condensation within the hydrophobic microchambers, leading to the formation of organised arrays of cellular spheroids. The microchambers were also designed to provide boundary conditions to these spheroids, guiding their growth and eventual fusion, leading to the development of stratified cartilage tissue with a depth-dependant collagen fiber architecture that mimicked the structure of native articular cartilage. Furthermore, the composition and biomechanical properties of the bioprinted cartilage was also comparable to the native tissue. Using multi-tool biofabrication, we were also able to engineer anatomically accurate, human scale, osteochondral templates by printing this microchamber system on top of a hypertrophic cartilage region designed to support endochondral bone formation and then maintaining the entire construct in long-term bioreactor culture to enhance tissue development. This bioprinting strategy provides a versatile and scalable approach to engineer structurally organised cartilage tissues for joint resurfacing applications.
成功的组织工程需要生成模仿天然组织结构、组成和机械性能的人类规模植入物。在这里，我们报告了一种新的生物制造策略，通过在 3D 打印聚合物微室阵列中引导细胞球体的生长，从而能够工程结构化组织。为了工程化分层关节软骨，我们使用喷墨生物打印将定义数量的间充质基质细胞 (MSCs) 和软骨细胞沉积到预先打印的微室中。这些喷射的细胞悬浮液在疏水性微室中迅速发生凝聚，导致细胞球体的有序阵列形成。微室还被设计为对这些球体提供边界条件，引导它们的生长和最终融合，从而形成具有深度依赖胶原纤维结构的分层软骨组织，模拟天然关节软骨的结构。此外，生物打印软骨的组成和生物力学特性也与天然组织相当。使用多工具生物制造，我们还能够通过在设计用于支持软骨内骨形成的肥大软骨区域上打印这种微室系统，然后将整个构建体在长期生物反应器培养中保持，以增强组织发育，从而工程化制造出解剖学上准确的、人类规模的、骨软骨模板。这种生物打印策略为关节表面工程提供了一种通用且可扩展的方法结构化组织软骨组织。
