Minocycline hydrochloride loaded on titanium by graphene oxide: an excellent antibacterial platform with the synergistic effect of contact-killing and release-killing

Abstract

Titanium and its alloys have been widely used in orthopedic and dental implants because of their excellent properties. However, implant failures still occur due to implant-associated bacterial infections. Therefore, proper surface modification of titanium and its alloys is necessary. In this work, commercial pure titanium plates were modified with graphene oxide (GO) which was used to load minocycline hydrochloride. Gram-positive Staphylococcus aureus (S. aureus) and Streptococcus mutans (S. mutans) and Gram-negative Escherichia coli (E. coli) were used to investigate the antibacterial activity of the samples. Human gingival fibroblast (HGF) cells were applied to assess the cytocompatibility of the various samples. To investigate cell adhesion and cell surface coverage in the presence of bacteria, the coculture of HGF cells and S. aureus was performed. The results indicated that the GO-modified titanium surface could inhibit the growth of the bacteria which had direct contact with GO, while it could not affect the bacteria without direct contact of GO. Minocycline hydrochloride on the GO-modified titanium surface (M@GO-Ti) showed a slow release behavior and exhibited excellent antibacterial activity with the synergistic effect of contact-killing and release-killing by GO and minocycline hydrochloride, respectively. In the coculture process with the presence of S. aureus, HGF cells on M@GO-Ti demonstrated the best cell viability and cell surface coverage among all the samples.

Corrosion Motivated ROS Generation Helps Endow Titanium with Broad‐Spectrum Antibacterial Abilities

“…However, peaks corresponding to Mg–Fe LDHs disappeared after minocycline loading, indicating a lower crystallinity of Mg–Fe LDHs on M‐LDH samples. Raman spectra of M‐Ti and M‐LDH show distinct peaks centered around 1310 and 1620 cm −1 (Figure c), corresponding the Raman shift of minocycline . The peak intensity of M‐LDH is stronger than that of M‐Ti samples, revealing more antibiotics were loaded on the M‐LDH samples.…”

“…Here we report an antibiotic loading film as a qualified corrosion‐motivated ROS generating platform, to endow titanium with broad‐spectrum antibacterial effect. In which we chose minocycline hydrochloride, a commonly used antibiotic, as the model drug, and selected Mg–Fe layered double hydroxides (LDHs) films to help ROS production. The platform is thus denoted as “M‐LDH.” Mg–Fe LDHs are p‐type semiconductors, while titanium oxides (TiO 2 ) that automatically formed on titanium surface are n‐type semiconductors.…”

Review of titanium surface modification techniques and coatings for antibacterial applications

“…[173] The importance of the number of GO layers was shown by Qiu et al [174] In fact, increasing the layer number of GO resulted in enhanced antibacterial and osteogenic effects compared to pure titanium controls. Qian et al [175] studied minocycline-loaded GO and successfully established a combination of direct contact killing by GO and delayed release-killing by minocycline hydrochloride on S. aureus, S. mutans and E. coli with no detrimental effect on cytocompatibility (human gingival fibroblasts).…”

Preparing and immobilizing antimicrobial osteogenic growth peptide on titanium substrate surface

“…It is worth mentioning that antibiotics (e.g., vancomycin, gentamicin, ciprofloxacin—though may induce bacterial antibiotic resistance) are widely used as they can rapidly and effectively against a broad spectrum of bacteria . Ciprofloxacin (CIP), as a representative synthetic antimicrobial agent, is efficaciously against both Gram‐positive and ‐negative strains, including some strains resistant to penicillin, cephalosporins, and aminoglycosides .…”

“…It is worth mentioning that antibiotics (e.g., vancomycin, gentamicin, ciprofloxacin-though may induce bacterial antibiotic resistance) are widely used as they can rapidly and effectively against a broad spectrum of bacteria. 17,[36][37][38][39] Ciprofloxacin (CIP), as a representative synthetic antimicrobial agent, is efficaciously against both Gram-positive and -negative strains, including some strains resistant to penicillin, cephalosporins, and aminoglycosides. [40][41][42][43] Except for the broad spectrum antimicrobial activity, CIP is the least expensive drug in the fluoroquinolone family and is already FDA approved and indicated for bone and joint infections.…”