title: The effect of integrin-specific bioactive coatings on tissue healing and implant osseointegration.
abstract: Implant osseointegration, defined as bone apposition and functional fixation, is a requisite for clinical success in orthopaedic and dental applications, many of which are restricted by implant loosening. Modification of implants to present bioactive motifs such as the RGD cell-adhesive sequence from fibronectin (FN) represents a promising approach in regenerative medicine. However, these biomimetic strategies have yielded only marginal enhancements in tissue healing in vivo. In this study, clinical-grade titanium implants were grafted with a non-fouling oligo(ethylene glycol)-substituted polymer coating functionalized with controlled densities of ligands of varying specificity for target integrin receptors. Biomaterials presenting the alpha5beta1-integrin-specific FN fragment FNIII 7-10 enhanced osteoblastic differentiation in bone marrow stromal cells compared to unmodified titanium and RGD-presenting surfaces. Importantly, FNIII 7-10-functionalized titanium significantly improved functional implant osseointegration compared to RGD-functionalized and unmodified titanium in vivo. This study demonstrates that bioactive coatings that promote integrin binding specificity regulate marrow-derived progenitor osteoblastic differentiation and enhance healing responses and functional integration of biomedical implants. This work identifies an innovative strategy for the rational design of biomaterials for regenerative medicine.
authors.affiliation: Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA 30332, United States.
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Petrie
authors.forename: Jenny E
authors.initials: JE
authors.lastname: Raynor
authors.forename: Catherine D
authors.initials: CD
authors.lastname: Reyes
authors.forename: Kellie L
authors.initials: KL
authors.lastname: Burns
authors.forename: David M
authors.initials: DM
authors.lastname: Collard
authors.forename: Andrés J
authors.initials: AJ
authors.lastname: García
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D016023:Integrins / Q000737:chemistry*; D016348:Osseointegration; D051381:Rats; D014945:Wound Healing
chemical_list: D016023:Integrins