Stem cell homing using local delivery of plerixafor and stromal derived growth factor-1alpha for improved bone...

Triggering of the early healing events, including the recruitment of progenitor cells, has been suggested to promote bone regeneration. In implantology, local drug release technologies could provide an attractive approach to promote tissue regeneration. In this study, we targeted the chemotactic SDF-1α/CXCR4 axis that is responsible e.g. for the homing of stem cells to trauma sites. This was achieved by local delivery of plerixafor, an antagonist to CXCR4, and/or SDF-1α, from titanium implants coated with mesoporous titania thin films with a pore size of 7.5 nm. In vitro drug delivery experiments demonstrated that the mesoporous coating provided a high drug loading capacity and controlled release. The subsequent in vivo study in rat tibia showed beneficial effects with respect to bone-implant anchorage and bone-formation along the surface of the implants when plerixafor and SDF-1α were delivered locally. The effect was most prominent by the finding that the combination of the drugs significantly improved the mechanical bone anchorage. These observations suggest that titanium implants with local delivery of drugs for enhanced local recruitment of progenitor cells have the ability to promote osseointegration. This approach may provide a potential strategy for the development of novel implant treatments. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2466-2475, 2016.