title: Stem cell homing using local delivery of plerixafor and stromal derived growth factor-1alpha for improved bone regeneration around Ti-implants.
abstract: 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.
authors.affiliation: Department Of Chemistry and Chemical Engineering, Applied Chemistry, Chalmers University of Technology, Gothenburg, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Karlsson
authors.affiliation: Department Of Fibre and Polymer Technology, KTH Royal Institute of Technology, Stockholm, Sweden.
authors.forename: Necati
authors.initials: N
authors.lastname: Harmankaya
authors.affiliation: Department Of Biomaterials, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Palmquist
authors.affiliation: Department Of Chemistry and Chemical Engineering, Applied Chemistry, Chalmers University of Technology, Gothenburg, Sweden.
authors.forename: Saba
authors.initials: S
authors.lastname: Atefyekta
authors.affiliation: Department Of Biomaterials, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Omar
authors.initials: O
authors.lastname: Omar
authors.affiliation: Department Of Biomaterials, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Pentti
authors.initials: P
authors.lastname: Tengvall
authors.affiliation: Department Of Chemistry and Chemical Engineering, Applied Chemistry, Chalmers University of Technology, Gothenburg, Sweden.
authors.forename: Martin
authors.initials: M
authors.lastname: Andersson
mesh_terms: D000818:Animals; D001596:Benzylamines; D001861:Bone Regeneration / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D054377:Chemokine CXCL12 / Q000008:administration & dosage* / Q000494:pharmacology; D020099:Coated Materials, Biocompatible / Q000737:chemistry*; D000080027:Cyclams; D003692:Delayed-Action Preparations / Q000737:chemistry*; D016503:Drug Delivery Systems; D006571:Heterocyclic Compounds / Q000008:administration & dosage* / Q000494:pharmacology; D008297:Male; D016348:Osseointegration / Q000187:drug effects; D010012:Osteogenesis / Q000187:drug effects; D016062:Porosity; D017207:Rats, Sprague-Dawley; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors*; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects*; D014025:Titanium / Q000737:chemistry*
chemical_list: D001596:Benzylamines; D054377:Chemokine CXCL12; D020099:Coated Materials, Biocompatible; D000080027:Cyclams; D003692:Delayed-Action Preparations; D006571:Heterocyclic Compounds; D019718:Receptors, CXCR4; C009495:titanium dioxide; D014025:Titanium; C088327:plerixafor
keywords: biomedical implants; cell homing; controlled drug delivery; mesoporous materials; osseointegration