FOR 2180:  Graded Implants for Tendon-Bone Junctions (“Graded Implants”)

• Subject Area: Materials Science and Engineering ; Biology ; Chemistry ; Medicine
• Term: from 2015 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 251503496

Implant research recently focusses on functional tissue implants forhomogenous tissues. Less well elaborated are implants for regionsbetween tissues with strongly differing properties, e. g. tendon-bonejunctions. Natural tissue junctions exhibit gradients: gradients instructure, composition, and resulting functionality which are reflectedby alterations in biomechanical properties. This complex situation isaddressed by the novel, graded cell-free implant presented by theresearch unit. Endogenous stem cells from the host shall be activatedand instructed by the implant to rebuild a tendon-bone junction and toachieve a functional (“regenerated”) junction after degradation of theimplant. Aim of the research unit is to demonstrate the principlefeasibility and to generate a model of a graded implant for futureapplications at the tendon-bone junction of the rotator cuff. As basicmaterial, electrospun fibre mats from biodegradable polymers (mainlybased on polycaprolactone) with isotropic (“on the tendon side”) oranisotropic (“on the bone side”) fibre orientation will be used. The fibremats will be equipped with appropriate porosity and permeability toallow for the survival and functionality of immigrating cells as well asthe exchange of nutrients and products of metabolism. In addition, themechanical properties will be tailored according to the in vivosituation.Fibre surfaces will be modified and equipped with varyingdegrees of nanoparticles: polymeric nanoparticles will serve asrelease systems for biologically active proteins. Apart from BoneMorphogenetic Protein (BMP)-2 and Transforming Growth Factor(TGF)-β, the novel factor Smad8 Linker region + Mad homologyregion 2 (Smad8 L+MH2) will be used. This is a modified transcriptionfactor inducing differentiation of cells into tendon cells and tendontissue. By targeted design of the nanoparticles and by use of methodsfor their (graded) immobilization on the fibre mat release kinetics ofthe factors will be adjusted according to biological needs. In order toachieve long-term release also BMP2-aggregates and amyloidvariants of Smad8 L+MH2 will be produced. Fixation of the implant onthe bone side will by performed by commercially available boneanchors. At the tendon side, sutures will be used. The formation of aregenerated tissue junction after use of the implant will be verified inthe research unit by use of small and large animal models. Inconclusion, gradients existent in vivo will be translated into gradientsof mechanical properties in combination with spatially and temporallycontrolled release of biologically active proteins within FOR 2180.

• DFG Programme: Research Units
• International Connection: Australia, Austria

Projects

• Biology and function of the signaling factors BMP2, TGF-beta3, Smad8 L+MH2 (Applicant Hoffmann, Andrea )
• Coordination Funds (Applicant Hoffmann, Andrea )
• Cytocompatibility and bioactivity testing in vitro (Applicant Weyand, Birgit )
• Development of processes for the production of the signaling factors BMP-2, TGF-ß3, Smad8 L MH2 as well as novel variants with defined stabilities (Applicants Rinas, Ursula ;  Scheper, Thomas )
• Fabrication of electrospun fibre mats with defined geometry and load profile (Applicant Glasmacher, Birgit )
• In vivo application, biomechanical evaluation (Applicants Kampmann, Andreas ;  Reifenrath, Janin )
• Polymers and Fiber Surfaces (Applicant Menzel, Henning )
• Quantification of release and activity of the signaling factors BMP-2, TGF-ß3, Smad8 L+MH2 (Applicants Bunjes, Heike ;  Hoffmann, Andrea )
• Systems for binding and release of growth factors (Applicant Menzel, Henning )

• Spokesperson: Professorin Dr. Andrea Hoffmann