Preparing and immobilizing antimicrobial osteogenic growth peptide on titanium substrate surface

Abstract

The inherent bioinertness and potential bacterial infection risk are the two leading causes for Ti implant failure. To improve osseointegration and antibiosis, in this work, a novel antimicrobial osteogenic growth peptide was first synthesized by conjugating osteogenic growth peptide (OGP) and ciprofloxacin (CIP). Then, the synthetic antimicrobial peptide was immobilized onto Ti implant surface for chemoselective binding via the amide reaction. Thereafter, the capabilities of modified Ti implant on osseointegration and antibiosis were measured with cell experiments and antimicrobial activity in vitro. The results showed that antimicrobial osteogenic growth peptide (OGP-CIP) was successfully prepared and grafted onto Ti implant surface. Moreover, the antimicrobial peptide-modified Ti implants could promote osteoblasts spreading and osteodifferentiation compared with unmodified Ti substrates. Meanwhile, in vitro bacteria studies (Staphylococcus aureus and Escherichia coli) proved that the antibacterial property of antimicrobial peptide functionalized Ti implant was improved obviously. The method used in this work is a feasible and promising strategy to win the race against invading bacteria and accelerate bone integration in orthopedic implantation. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 3021-3033, 2018.

<p>Magnesium-doped Nanostructured Titanium Surface Modulates Macrophage-mediated Inflammatory Response for Ameliorative Osseointegration</p>

“…In order to successfully install the implants, researchers make efforts to create bioactive coating materials on titanium surface using different techniques. 1 , 2 In these studies, favorable osteogenic, angiogenic and antibacterial capacities of coating materials have been widely explored. 3 , 4 However, many coating materials with excellent properties mentioned above could not achieve satisfactory results in the subsequent in vivo studies in terms of the regeneration of bones.…”

Construction of Local Drug Delivery System on Titanium-Based Implants to Improve Osseointegration

“…They demonstrated that the release of chlorhexidine could facilitate osseointegration by completely preventing the formation of bacterial biofilm on the implant surface [ 96 ]. In addition, the failure of osseointegration caused by bacterial infection could be prevented by direct grafting of antibiotic ciprofloxacin on Ti implants or by loading ciprofloxacin on CS/nanoHA/Ti [ 97 , 98 ]. In order to obtain more superior antibacterial implants, Park et al loaded silver nanoparticles, cephalothin, minocycline (Mino), and amoxicillin on mesoporous TiO 2 .…”

Surface engineering of biomaterials in orthopedic and dental implants: Strategies to improve osteointegration, bacteriostatic and bactericidal activities

“…Induced in vitro mineralization [29] SiO 2 /MgO doped HA -plasma spraying -↑ In vivo osteogenesis and osteointegration [35] Chitosan/gelatin/HA -LBL assembly -↑ Adhesion, proliferation and osteogenic differentiation of MSCs ↑ Adhesion and mitigation of HUVECs ↑ In vivo osteogenesis and angiogenesis [151] TNT -electrochemical anodization CaP -biomimetic coating -↑ Early stage in vivo osteointegration and mineralization [23] Ti6Al4V HA -plasma spraying ↑ Surface roughness ↑ Adhesion and attachment of osteoblast ↓ Osteosarcoma ↑ In vivo osteointegration [16] HA -magnetron sputtering Homogeneous crystalline coating - [24] Si doped HA -dip coating VEGF -physical adsorption ↑ Proliferation of pre-osteoblasts and endothelial cells ↑ In vivo osteointegration and angiogenesis in osteoporotic model [30] Biphasic CaP nHA -hydrothermal deposition -↑ Viability and osteogenic differentiation of MSC PEG -electrodeposition RGD/LF1-11 -covalent immobilization ↑ Hydrophilicity ↑ Osteoblast adhesion and spreading ↓ Adhesion and viability of S. sanguinis and protein adsorption [132] GL13K (AMP) -covalent immobilization ↑ Hydrophilicity Slightly ↑ surface roughness ↓ Viability of P. gingivalis ↑ Fibroblast viability and attachment [110] Osteogenic growth peptide/ciprofloxacin -covalent immobilization ↑ Hydrophilicity → Surface roughness ↑ Osteoblast spreading and osteodifferentiation [111] NO releasing coating -silanization, diazeniumdiolate functionalization ↓ Hydrophilicity ↑ Surface roughness ↓ Adhesion and colonization of S. aureus and P. aeruginosa No cytotoxicity to osteoblasts [161] Ag/PDA -physical adsorption -↓ Growth and colonization of S. mutans and P. gingivalis [162] Ag NPs/GO -electroplating Microstructured ↓ Adhesion and viability of S. mutans and P. gingivalis ↑ Cytotoxicity with higher GO and Ag NPs [163] GL13K/TNT -physical adsorption/electrochemical anodization -↓ Growth of F. nucleatum and P. gingivalis ↑ Proliferation and no cytotoxicity to MC3T3-E1 cells [124] Ag NPs/ vancomycin/TNTs -plasma immersion ion implantation (PIII)/lyophilization/electrochemical anodization -↓ Adhesion of S. aureus No cytotoxicity to fibroblasts [123] Ag ↑: enhancement; ↓: hindered effect; →: comparable result.…”

“…A dual functional AMP was synthesized by conjugating osteogenic growth peptide with ciprofloxacin, and covalently immobilized on titanium surface. [ 111 ] Such AMP modified titanium promoted proliferation, spreading and osteogenic differentiation of osteoblasts. The sustained release of this AMP for 7 days led to less adhered and viable bacteria.…”