Investigating the synergistic effects of spatially resolved biochemical, physicochemical, and physical key stimuli to generate biomimetic niches in perfusion bioreactor and their proficiency to derive large bone-like constructs.

研究空间分辨的生化、物理化学和物理关键刺激的协同效应，以在灌注生物反应器中产生仿生生态位，以及它们衍生大型骨样结构的能力。

• 批准号: 460388836
• 负责人: Dr.-Ing. Benjamin Kruppke
• 金额: --
• 依托单位: Fraunhofer-Institut für Keramische Technologien und Systeme (IKTS)
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/460388836?language=en
• 关键词: Investigating; synergistic; effects; spatially; resolved

Bioreactors are used increasingly in bone tissue engineering approaches, but the existing homogenous niche applied is generally insufficient to achieve/support formation of bone-like constructs. In physiology, multiple osteochondral cells are present in high cell density and their dynamic interactions are critical for bone development and regeneration processes. This is also complemented with supporting parameters such as oxygen tension (pO2) distribution, biochemical stimuli, and physical/mechanical stimuli to establish the dynamic niches essential for the growth of naïve organs (i.e. cartilage and bone) and attaining their functionalities.In this proposal, we aim to investigate the synergistic potentials of 5 distinct parameters to recapitulate bone developmental processes in a perfusion bioreactor. Through the established dynamic biomimetic niches, the effects on construct development and capability to achieve bone-like tissues in vitro will be assessed. These parameters include 1) medium pH; 2) pO2; 3) Young´s modulus of 3D-printed scaffolds; 4) multi-step osteochondral differentiation regimes and 5) Transformer-like induced electric field (TLC-EF) stimulation to emulate piezoelectric stimuli during movement.Human bone marrow-derived mesenchymal stem cells (hMSC) and human induced pluripotent stem cells (hiPSC) will be used to define the proficiency of biomimetic niches. Their potential to derive different osteochondral cell-types in the biomimetic niches will be critically assessed. Specifically for TLC-EF stimulations, multiscale modeling/simulations that describe EF/Bone construct interactions and the effects on osteogenesis will be combined with experimental validations. This is done with the aim to define an effective range of EF parameters for bone tissue engineering applications. Ultimately, this study will result in a specific set of conditions/stimuli that can recapitulate physiological-like niches in vitro. The approaches applied will also introduce a novel concept to the field of tissue engineering and can be further exploited to derive bone-like constructs with near-physiological properties in a bioreactor.

生物反应器越来越多地用于骨组织工程方法，但现有的同质龛应用通常不足以实现/支持骨样结构的形成。在生理学上，多个骨软骨细胞以高细胞密度存在，它们的动态相互作用对骨发育和再生过程至关重要。这也是补充支持参数，如氧分压（pO 2）分布，生化刺激，和物理/机械刺激，以建立幼稚器官（即软骨和骨）的生长和实现其functionals.In本提案中，我们的目标是调查的协同潜力5个不同的参数，以概括骨发育过程中的灌注生物反应器。通过建立的动态仿生生态位，将评估对构建体发育和体外获得骨样组织的能力的影响。这些参数包括1）介质pH值; 2）pO 2; 3）3D打印支架的杨氏模量; 4）多步骨软骨细胞分化方案和5）在运动期间模仿压电刺激的类变压器诱导电场（TLC-EF）刺激。将被用来定义仿生生态位的熟练程度。他们的潜力，以获得不同的骨软骨细胞类型的仿生龛将严格评估。特别是对于TLC-EF刺激，描述EF/骨结构相互作用和对骨生成影响的多尺度建模/模拟将与实验确认相结合。这样做的目的是定义骨组织工程应用的EF参数的有效范围。最终，这项研究将导致一组特定的条件/刺激，可以概括体外生理学样壁龛。所应用的方法也将引入一个新的概念，组织工程领域，并可以进一步利用生物反应器中获得具有接近生理特性的骨样结构。