Cell-scaffold interactions in artificial bone: regulation of collagen-I networks and focal adhesion complexes by biochemical and environmental cues

人造骨中细胞支架的相互作用：生化和环境因素对 I 型胶原蛋白网络和粘着斑复合物的调节

• 批准号: 410498501
• 负责人: Professor Dr. Oliver Friedrich
• 金额: --
• 依托单位: Lehrstuhl für Medizinische Biotechnologie (MBT)
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2018
• 资助国家: 德国
• 起止时间: 2017-12-31 至 2022-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/410498501?language=en
• 关键词: Cell; scaffold; interactions; artificial; bone; Cell; scaffold; interactions; artificial; bone

Collagen-I is the major fibrous extracellular component of bone responsible for its ultimate tensile strength. In tissue engineering (TE) one of the most important issues is to get cells inter-connected via a strong and functional extracellular matrix (ECM) mimicking as closely as possible naturally occurring ECM geometry. What is still missing is (i) a versatile, high-resolution and non-invasive online method to evaluate and quantify different aspects of engineered ECM and (ii) deeper insights into the mechanism as to why cellular ECM production is enhanced in 3D cell-scaffold composites, putatively via enhanced focal adhesion (FA) linkages, unlike in the 2D setting. The goal within this project is to develop such methods with collagen-I producing and bone forming cells based on multiphoton imaging (MPI) technologies, to use those techniques to compare collagen-I production and organization capabilities in 2D- and 3D-seeded constructs, to link them to the number, extension and distribution of FA complexes and to monitor changes due to biomechanical treatment of the constructs. Our major work hypothesis is that biomechanical stability of engineered bone tissue constructs is directly encoded by the angular distribution and fibrillary geometry of ECM collagen fibers, and high stability occurs within more isotropic interwoven fibrils as a result of activation of increased FA complex formation with ascorbic acid playing a critical role in the regeneration of collagen-I with optimum fiber stability.

胶原蛋白I是负责其最终拉伸强度的骨外细胞外成分。在组织工程（TE）中，最重要的问题之一是通过强大且功能性的细胞外基质（ECM）与模拟自然发生的ECM几何形状相互关联。仍然缺少的是（i）一种多功能，高分辨率和非侵入性在线方法，用于评估和量化工程ECM的不同方面，以及（ii）通过增强的焦点（FA）链接（FA）链接（不在2D设置）中，对3D细胞型Foss材料的细胞ECM生产的更深入的见解。 The goal within this project is to develop such methods with collagen-I producing and bone forming cells based on multiphoton imaging (MPI) technologies, to use those techniques to compare collagen-I production and organization capabilities in 2D- and 3D-seeded constructs, to link them to the number, extension and distribution of FA complexes and to monitor changes due to biomechanical treatment of the constructs. Our major work hypothesis is that biomechanical stability of engineered bone tissue constructs is directly encoded by the angular distribution and fibrillary geometry of ECM collagen fibers, and high stability occurs within more isotropic interwoven fibrils as a result of activation of increased FA complex formation with ascorbic acid playing a critical role in the regeneration of collagen-I with optimum fiber stability.