Three-dimensional matrix-based models for dental tissue engineering

基于3D(维度)细胞的体外模型的可用性是口腔健康研究和牙科行业面临的一个日益重大的挑战。不断上升的总交付成本以及当前体外模型和检测的糟糕预测价值，将重点放在开发更现实的基于细胞的3D模型和检测上。准确和高效的体外模型具有巨大的价值，因为它们允许在药物测试中做出早期和基于知识的决定。在模拟牙槽骨系统的生物反应器系统中，基于不同细胞的三维基质模型在组织工程、再生医学和药物开发方面具有巨大的潜力。开发3D牙槽组织结构的主要挑战是表征结构中活的、与生物相关的细胞，以及模拟体内条件的环境因素的应用。与现有的基于2D单一培养的方法相比，这些模型将在速度、精度和规模方面具有优势。这些基于3D模型的技术对于理解疾病过程和药物发现至关重要。 我的实验室最近出现在这一新兴领域的前沿，这是因为我们利用基于细胞培养的模型对纳米材料进行了表征，对来自顶端乳头的干细胞、巨噬细胞和巨噬细胞-干细胞相互作用进行了实验。我们研究了齿骨结构的生物力学，这是在三维牙槽模型中模拟环境因素的关键。此外，我们最近将快速崛起的3D打印技术应用于打印模具的努力，产生了一种在3D工程牙齿组织中定位免疫细胞和干细胞的新方法。 在我们已有的工作和最近的成功基础上，这项研究计划的短期目标是在生物反应器平台上开发和表征基于3D基质的体外组织结构，以模拟活体牙周组织。将开发互补的快速检测方法，以确定细胞的形态、迁移、增殖、分化和凋亡。利用这一认识，我们将专注于开发新的基于解剖学的设计，将免疫/干细胞与细胞外基质整合到牙槽装置的构造中。这些模型将有助于理解免疫细胞和干细胞在促炎和抗炎条件下以及在存在免疫调节纳米颗粒的情况下相互作用的机制。 从长远来看，我们将开发集成的体外3D牙槽组织构建生物反应器平台，以降低成本，提高产量，并针对药物发现或生物研究中的特定应用实现快速分析的自动化。这些系统的成本效益和增强的能力将提高制药、生物和生物医学研究人员的生产率

The availability of in vitro 3D (dimensional) cell-based models that mimics in vivo dento-alveolar tissues is a progressively significant challenge facing oral health research and dental industry. The rising total-delivered-cost as well as the poor predictive value of the current in vitro models and assays, place great emphasis on the development of more realistic 3D cell-based models and assays. Accurate and efficient in vitro models are of enormous value, since they permit early and knowledge-based decisions in drug testing. 3D matrix-based models with different cells, in a bioreactor system that simulate dentoalveolar system, holds great potential for tissue engineering, regenerative medicine and drug discovery. The main challenge in developing 3D dentoalveolar tissue constructs is the characterization of living, biologically relevant cells in the constructs and the application of environmental factors that mimics in vivo conditions. These models will confer the advantage of speed, accuracy and scale over existing 2D monoculture-based methods. These 3D model-based technologies are critically important for understanding disease process and drug discovery. My laboratory has recently emerged at the forefront of this nascent field due to our established work on nanomaterial characterization using cell culture-based models, experiments on stem cells from apical papillae, macrophages and macrophage-stem cell interactions. We have worked on the biomechanics of dento-osseous structures, which is key to simulate environmental factors in 3D dentoalveolar models. In addition, our recent efforts to adapt the rapidly emerging 3D printing technology to print molds, generated a novel way to position immune cells and stem cells in the 3D engineered dental tissue like constructs. Building on our established work and recent success, the short term aim of this research program is to develop and characterize in vitro 3D matrix-based tissue constructs in a bioreactor platform to simulate in vivo periodontium. Complementary rapid assays will be developed for determining cell morphology, migration, proliferation, differentiation and apoptosis. Using that understanding, we will focus on developing new anatomically-based designs to integrate immune/stem cells with extracellular matrix in the constructs of dentoalveolar apparatus. These models will aid in understanding the mechanisms of interaction between immune cells and stem cells in pro- and anti-inflammatory conditions, as well as in the presence of immune modulatory nanoparticles. Over the long term we will develop integrated in vitro 3D dentoalveolar tissue constructbioreactor platform that lower the cost, increase throughput and automate rapid assays targeted towards specific applications in drug discovery or biological research. These systems by its cost effectiveness and enhanced capabilities will improve the productivity of pharmaceutical, biological and biomedical researchers