The effect of integrin-specific bioactive coatings on tissue healing and implant osseointegration.
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.
Petrie
Timothy A
TA
Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA 30332, United States.
Raynor
Jenny E
JE
Reyes
Catherine D
CD
Burns
Kellie L
KL
Collard
David M
DM
García
Andrés J
AJ
D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D016023:Integrins / Q000737:chemistry*; D016348:Osseointegration; D051381:Rats; D014945:Wound Healing
D016023:Integrins