A successful osseointegration of orthopedic implants requires a strong mechanical interaction between the surface of the biomaterial and the surrounding natural bone tissue. This biological process is determined by initial cell-biomaterial interactions. In the last decades scientists in the fields of material science, surface engineering, chemistry, physics, biology, biochemistry and medicine attempted to functionalize the surfaces of implants with bioactive molecules in order to enable signaling to adjacent cells and to obtain a rapid and specific cell colonization directly on the material surface.
Mimicking the physiological adhesion process of osteoblasts to the extracellular matrix (ECM), by coating of implant surfaces with specific cell-adhesive molecules, was proven to enhance osteoblast adhesion in vitro and accelerate osseointegration of implants in vivo. Cell adhesion is mediated by integrins, a family of heterodimeric transmembrane glycoproteins, which regulate cell-ECM and cell-cell interactions. The peptide sequence Arg-Gly-Asp (RGD) is by far the most effective and extensively studied ligand to promote osteoblast adhesion and proliferation on implants through integrin stimulation.
The goal of this project is to optimize the biofunctionalization of different orthopedic implants with av-specific integrin ligands in order to develop clinically effective biomaterials for bone grafting in humans (see Figure). Each of the components of the coating system (implant material, anchor, spacer and specific integrin ligand) should be considered and studied in detail for the design of successful biomimetic materials.
Mas-Moruno, C., Dorfner, P.M., Manzenrieder, F., Neubauer, S., Reuning, U., Burgkart, R., Kessler, H.: “Behaviour of primary human osteoblasts on trimmed and sandblasted Ti6AI4V surfaces functionalized with integrin avb3-selective cyclic RGD peptides”, 2012.
Schottelius, M., Laufer, B., et al.: "Ligands for Mapping alpha_nbeta_3-Integrin Expression in Vivo”, 2009.
Heckmann, D., Laufer, B., et. al: "Breaking the Dogma of the Metal-Coordinating Carboxylate Group in Integrin Ligands: Introducing Hydroxamic Acids to the MIDAS To Tune Potency and Selectivity", 2009.
Laufer, B., et al: "Can N-methylated amino acids serve as substitutes for prolines in conformational design of cyclic pentapeptides?", 2009.
Knor, S., Khrenov, A., Laufer, B., et. Al: "Efficient factor VIII affinity purification using a small synthetic ligand", 2008.
Heckmann, D., Meyer, A., Laufer, B., et. al: "Rational Design of Highly Active and Selective Ligands for the alpha5beta1 Integrin Receptor”, 2008.
Kummerlöwe, G., Halbach, F., Laufer, B., Luy, B.: "Precise measurement of RDCs in water and DMSO based gels using a silicone rubber tube for tunable stretching", 2008.
Knör, S., Khrenov, A., Laufer, B., et. Al: "Development of a Peptidomimetic Ligand for Efficient Isolation and Purification of Factor VIII via Affinity Chromatography", 2007.
Knör, S., Laufer, B., Kessler, H.: "Efficient Enantioselective Synthesis of Condensed and Aromatic-Ring-Substituted Tyrosine Derivatives", 2006.