Coordination Funds

植入物研究最近集中在同质组织的功能性组织植入物上。不太详细的是用于具有强烈不同性质的组织之间的区域的植入物，例如肌腱-骨连接。自然组织连接呈现梯度：结构、组成和由此产生的功能的梯度，其通过生物力学性质的改变来反映。这种复杂的情况是由研究单位提出的新型分级无细胞植入物解决的。来自宿主的内源性干细胞应被植入物激活并指导重建肌腱-骨连接，并在植入物降解后实现功能性（再生）连接。该研究单位的目的是证明原则的可行性，并生成一个模型的梯度植入物的未来应用在肌腱肌腱-骨交界处的肩袖。作为基本材料，静电纺丝纤维垫从生物降解聚合物（主要是基于聚己内酯）具有各向同性（）或各向异性（）纤维取向将被使用。纤维垫将具有适当的孔隙率和渗透性，以允许迁移细胞的生存和功能以及营养物质和代谢产物的交换。此外，将根据体内情况定制机械性能。纤维表面将被改性，并配备不同程度的磷酸钙，二氧化硅或聚合物纳米颗粒。二氧化硅或聚合物纳米颗粒将作为生物活性蛋白质的释放系统。除骨形态发生蛋白（BMP）2和转化生长因子（TGF）-β外，还将使用Smad 8连接区+ Mad同源区2（Smad 8 L+ MH 2）。这是一种修饰的转录因子，诱导细胞分化为肌腱细胞和肌腱组织。对于释放动力学的受控操作，将通过纳米颗粒释放系统以分级方式应用因子。为了实现长期释放，还将产生蛋白质的淀粉样蛋白变体。将通过市售骨锚钉将植入物固定在骨侧。在肌腱侧，将使用缝线。将在研究单位通过使用小型和大型动物模型验证植入物使用后再生组织连接的形成。

Implant research recently focusses on functional tissue implants for homogenous tissues. Less well elaborated are implants for regions between tissues with strongly differing properties, e.g. tendon-bone junctions. Natural tissue junctions exhibit gradients: gradients in structure, com-position, and resulting functionality which are reflected by alterations in biomechanical properties. This complex situation is addressed by the novel, graded cell-free implant presented by the re-search unit. Endogenous stem cells from the host shall be activated and instructed by the implant to rebuild a tendon-bone junction and to achieve a functional (¿regenerated¿) junction after degradation of the implant. Aim of the research unit is to demonstrate the principle feasibility and to generate a model of a graded implant for future applications at the tendon-bone junction of the rotator cuff.As basic material, electrospun fibre mats from biodegradable polymers (mainly based on polycaprolactone) with isotropic (¿on the tendon side¿) or anisotropic (¿on the bone side¿) fibre orientation will be used. The fibre mats will be equipped with appropriate porosity and permeability to allow for the survival and functionality of immigrating cells as well as the exchange of nutrients and products of metabolism. In addition, the mechanical properties will be tailored according to the in vivo-situation. Fibre surfaces will be modified and equipped with varying degrees of calcium phosphate, silica or polymeric nanoparticles. Silica- or polymeric nanoparticles will serve as re-lease systems for biologically active proteins. Apart from Bone Morphogenetic Protein (BMP)2 and Transforming Growth Factor (TGF)-¿, Smad8 Linker region + Mad homology region 2 (Smad8 L+MH2) will be used. This is a modified transcription factor inducing differentiation of cells into ten-don cells and tendon tissue. For controlled manipulation of the release kinetics the factors will be applied via nanoparticulate release systems in a graded manner. In order to achieve long-term re-lease also amyloid variants of the proteins will be produced. Fixation of the implant on the bone side will by performed by commercially available bone anchors. At the tendon side, sutures will be used. The formation of a regenerated tissue junction after use of the implant will be verified in the research unit by use of small and large animal models.