Patterned biomaterial degradation to guide multicellular response, extracellular matrix deposition and in-vivo tissue formation.

在过去的十年中，在理解生物材料的物理特性（如基质刚度或几何形状）对体外细胞过程和组织形成的影响方面有了突破性的发现。然而，对于这些发现如何转化为体内情况，我们知之甚少。该项目的目的是为了更好地了解支架结构对体内组织再生的潜力和局限性。据推测，体内骨再生可以通过改变支架结构来改善。将具有明确几何形状的支架植入羊胫骨30mm临界尺寸缺损的愈合结果作为模型系统。将开发一种工具来表征体内形成的矿化组织的宏观3D分布，与支架表面曲率以及缺陷内的轴向和径向位置有关。随后，在选定的支架单位体积内，将使用组织学、拉曼光谱和小角度x射线散射对纤维和矿化组织形态与支架表面曲率的关系进行微观描述。这个项目的结果将是对体内组织再生如何受到支架结构的影响有更深入的了解。这样的理解对于未来的脚手架设计是必不可少的。

In the past decade there have been groundbreaking discoveries in the understanding of the influence of physical properties of biomaterials, such as the substrate stiffness or geometry, on cellular processes and tissue formation in vitro. Little is known, however, about how these findings translate to an in vivo scenario. The aim of this project is to gain improved understanding about the potential and limitations of the effect of the scaffold architecture on in vivo tissue regeneration. It is hypothesized that in vivo bone regeneration can be improved just by modifying the scaffold architecture. The healing outcome of an ovine, tibial, 30 mm critical-sized defect, where a scaffold with a well-defined geometry was implanted, is used as a model system. A tool will be developed to characterize the macroscopic 3D distribution of mineralized tissue formed in vivo, in relation to the scaffold surface curvature and to the axial and radial location within the defect. Following this, a microscopic description of the fibrous and mineralized tissue morphology in relation to the scaffold surface curvature, within selected scaffold unit volumes, will be performed using histology, Raman spectroscopy and small angle X-ray scattering. The outcome of this project will be a deeper understanding on how in vivo tissue regeneration is influenced by the scaffold architecture. Such understanding is essential for future scaffold design.