Coordination Funds

近年来，移植物研究主要集中在同质组织的功能性组织移植物上。不太完善的是组织之间具有强烈不同性质的区域的植入物，例如肌腱-骨连接。自然组织连接点表现出梯度：结构、组成和由此产生的功能的梯度，这些梯度通过生物力学特性的改变来反映。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在植入物的激活和指导下重建肌腱-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理的可行性，并为将来在肌腱-骨交界处的肩袖应用生成一个分级植入物的模型。作为基础材料，将使用由可生物降解聚合物（主要基于聚己内酯）制成的具有各向同性（肌腱侧）或各向异性（骨侧）纤维取向的静电纺纤维垫。纤维垫将配备适当的孔隙度和渗透性，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，机械性能将根据在体内的情况量身定制。纤维表面将被修改，并配备不同程度的磷酸钙、二氧化硅或聚合纳米颗粒。二氧化硅或聚合物纳米颗粒将作为生物活性蛋白的释放系统。除了骨形态发生蛋白（BMP）2和转化生长因子(TGF)-¿外，还将使用Smad8连接区域+ Mad同源区域2 （Smad8 L+MH2）。这是一种修饰的转录因子，可诱导细胞分化为ten-don细胞和肌腱组织。为了控制释放动力学，这些因子将通过纳米颗粒释放系统以分级方式应用。为了实现长期释放，淀粉样蛋白的变体也将产生。植体在骨侧的固定将由市售骨锚进行。在肌腱一侧，将使用缝合线。使用植入物后再生组织连接的形成将在研究单位通过使用小型和大型动物模型进行验证。

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.