Coordination Funds

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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.