Development of advanced healthy and diseased in vitro 3D glomerulus model for drug testing and understanding kidney disease mechanisms

肾脏通过调节水分、电解质和酸碱平衡，在维持体内动态平衡方面起着重要作用。除了分泌各种激素外，它还在调节红细胞生成和血压方面发挥着重要作用。为了了解肾脏疾病和进行药物测试，建立器官不同单位的体外功能模型将是有帮助的。尽管近端小管的一些模型在过去几年中已经被提出，但是关于肾小球的模型很少存在--肾小球是形成初级尿液的肾脏部分。主要的问题是模拟与过滤过程相关的相对较高的毛细管内压。在这个印德项目中，我们希望使用最先进的添加剂制造技术，如熔体电写，来制造能够承受生理压力的纤维管。这些管子将覆盖有肾小球细胞外基质(ECM)的成分，如胶原蛋白和层粘连蛋白，也将覆盖来自动物来源的肾小球的脱细胞ECM。在用组织特异性内皮细胞(管腔)和足细胞(外表面)种植管子后，这些结构将被整合到定制的灌流生物反应器中，从而允许内部(管腔)和外部空间的单独灌流。这个合作项目将结合两位申请者在生物材料、组织工程和添加剂制造领域的专业知识(Michael Gelinsky，TU Dresden)，以及从脱细胞组织中提取ECM，以及定制生物反应器系统的设计和制造(Falguni Pati，IIT Hyderabad)。

Kidney plays an important role in maintaining homeostasis in the body by regulating water, electrolytes, and the acid/base balance. Apart from secreting various hormones, it also plays an important role in regulating red blood cell production and blood pressure. For understanding kidney diseases and for drug testing it would be helpful to have functional in vitro models of the different units of the organ. Whereas a number of models for the proximal tubule have been proposed in the last years only few models for the glomerulus exist – which is the part of the kidney where primary urine is formed. Main problem is to mimic the relatively high internal pressure of capillaries which is relevant for the filtration processes.In this Indo-German project we want to use state-of-the-art additive manufacturing technologies like melt electrowriting to fabricate fibrous tubes which are able to withstand the physiological pressure. The tubes will be coated with components of the extracellular matrix (ECM) of the glomerulus like collagens and laminin and also with decellularised ECM from animal-derived kidney glomeruli. After seeding of the tubes with tissue-specific endothelial cells (lumen) and podocytes (external surface) the structures will be integrated in customised perfusion bioreactors which allow separate perfusion of both internal (tube lumen) and external spaces. Finally, the function and relevance of the model will be tested by applying known drugs.This collaborative project will combine the expertise of both applicants in the fields of biomaterials, tissue engineering and additive manufacturing (Michael Gelinsky, TU Dresden) and extraction from ECM from decellularised tissues and design and manufacturing of customized bioreactor systems (Falguni Pati, IIT Hyderabad).