Effects of spatio-temporal taylored presentation of multiple growth factors in a biomimetic multilayer coating on tiotanium implants and its effects on periimplant angiogenesis and osteogenesis

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Trauma, (degenerative) diseases and their medical treatment led to an increased case frequency of impaired enosseous integration of dental implants over the past decades. One approach towards both supporting the regeneration of the surrounding bone tissue and to improving the stable integration, is to equip implant surfaces with osteogenic signal molecules. Although numerous strategies to anchor signal molecules to implant surfaces have been presented and investigated, it was not possible to demonstrate significant effects in vivo up to date. This effect may result from one of the following restrictions that state-of-the-art coatings are typically facing: (i) technically limited concentration of surface bound growth factors; (ii) improper release kinetic and/or (iii) predominantly restriction to presenting only one growth factor species. However, a variety of different cell types (endothelial cells, mesenchymal precursors, osteoblasts and fibroblasts) and signaling pathways (influencing proliferation, matrix synthesis and angiogenic / osteogenic differentiation) are involved in angiogenesis and osteogenesis. Thus, it is highly promising to anchor and present a more complex collection of signaling molecules on implant surfaces for effective enhancement of periimplant angiogenesis and osteogenesis.Coatings composed of ECM molecules like sulfated glycosamino glycans (sGAG) deposited as nanometer-scale multilayers are an effective tool for creating a biomimetic matrix on the implant surface. Since many of the most important growth factors in angiogenic and osteogenic signaling cascades possess a binding domain with high affinity to sGAG molecules, these coatings are perfectly suited to deliver growth factors in a biomimetic concentration, milieu and release profile. Consequently, in this grant we will use biomimetic sGAG coatings to address the following tasks: i)establish spatio-temporal patterns in the presentation of growth factors by either varying the film architecture and/or applying printing techniques, ii) determine the extent to which matrix bound and released growth factors contribute to the biological response and iii)presentation of several different growth factors in one coating for effective periimplant angiogenesis and osteogenesis.