Modification of implants by antimicrobial peptides (AMPs) can improve the antimicrobial activity of the implants. However, AMPs have some cytotoxicity in vivo when they are exposed at body temperature. To tackle this challenge, we propose to develop a new approach to generating a smart antimicrobial surface through exposure of AMPs on the surface. A polydopamine film was first formed on the substrates, followed by the conjugation of a temperature-sensitive polymer, (N-isopropylacrylamide) (pNIPAM), to the film through atom transfer radical polymerization (ATRP). Then, AMPs were conjugated to the NIPAM on the resultant pNIPAM-modified surface through a click chemistry reaction. Because of the temperature-sensitive property of pNIPAM, the AMPs motif was more exposed to the external environment at room temperature (25 °C) than at body temperature (37 °C), making the surface present a higher antimicrobial activity at room temperature than at body temperature. More importantly, such a smart behavior is accompanied with the increased biocompatibility of the surface at body temperature when compared to the substrates unmodified or modified by AMPs or pNIPAM alone. Our in vivo study further verified that pNIPAM-AMP dual modified bone implants showed increased biocompatibility even when they were challenged with the bacteria at room temperature before implantation. These results indicate that the implants are antibacterial at room temperature and can be safely employed during surgery, resulting in no infection after implantations. Our work represents a new promising strategy to fully explore the antimicrobial property of AMPs, while improving their biocompatibility in vivo. The higher exposure of AMPs at room temperature (the temperature for storing the implants before surgery) will help decrease the risk of bacterial infection, and the lower exposure of AMPs at body temperature (the temperature after the implants are placed into the body by surgery) will improve the biocompatibility of AMPs.
The
use of antimicrobial peptides (AMPs)-functionalized titanium
implants is an efficient method for preventing bacterial infection.
However, the attachment of AMPs to the surface of titanium implants
remains a challenge. In this study, a “clickable” titanium
surface was developed by using a silane coupling agent with an alkynyl
group. The antimicrobial titanium implant was then constructed through
the reaction between the “clickable” surface and azido-AMPs
(PEG-HHC36:N3-PEG12-KRWWKWWRR) via click chemistry
of Cu(I)-catalyzed azide–alkyne cycloaddition (CuAAC). Such
an antimicrobial titanium implant, with an AMP density of 897.4 ±
67.3 ng/cm2 (2.5 ± 0.2 molecules per nm2) on the surface, exhibited good and stable antimicrobial activity,
inhibited 90.2% of Staphylococcus aureus and 88.1%
of Escherichia coli after 2.5 h of incubation, and
even inhibited 69.5% of Staphylococcus aureus after
4 days of degradation. The CCK-8 assay indicated that the antimicrobial
titanium implant exhibited negligible cytotoxicity to mouse bone mesenchymal
stem cells. In vivo assay illustrated that this implant
could kill 78.8% of Staphylococcus aureus after 7
days. This method has great potential for the preparation of antimicrobial
titanium implants and the prevention of infections in the clinic.
Biocompatibility of intraocular lens (IOL) is critical to vision reconstruction after cataract surgery. Foldable hydrophobic acrylic IOL is vulnerable to the adhesion of extracellular matrix proteins and cells, leading to increased incidence of postoperative inflammation and capsule opacification. To increase IOL biocompatibility, we synthesized a hydrophilic copolymer P(MPC-MAA) and grafted the copolymer onto the surface of IOL through air plasma treatment. X-ray photoelectron spectroscopy, atomic force microscopy and static water contact angle were used to characterize chemical changes, topography and hydrophilicity of the IOL surface, respectively. Quartz crystal microbalance with dissipation (QCM-D) showed that P(MPC-MAA) modified IOLs were resistant to protein adsorption. Moreover, P(MPC-MAA) modification inhibited adhesion and proliferation of lens epithelial cells (LECs) in vitro. To analyze uveal and capsular biocompatibility in vivo, we implanted the P(MPC-MAA) modified IOLs into rabbits after phacoemulsification. P(MPC-MAA) modification significantly reduced postoperative inflammation and anterior capsule opacification (ACO), and did not affect posterior capsule opacification (PCO). Collectively, our study suggests that surface modification by P(MPC-MAA) can significantly improve uveal and capsular biocompatibility of hydrophobic acrylic IOL, which could potentially benefit patients with blood-aqueous barrier damage.
In this article, we prepared hyaluronic acid/poly(amidoamine) dendrimer (HA/PAMAM) multilayers on a poly(3-hydroxybutyrate-co-4-hydroxybutyrate) [P(3HB-4HB)] substrate by a layer-by-layer self-assembly method for antimicrobial biomaterials. The results of ζ potential and quartz crystal microbalance with dissipation (QCM-D) showed that HA/PAMAM multilayers could be formed on the substrate layer by layer. We used QCM-D to show that both the HA outer layer and the PAMAM outer layer exhibited good protein-resistant activity to bovine serum albumin and bacterial antiadhesion activity to Escherichia coli. By a live/dead assay and the colony counting method, we found that the PAMAM outer layer could also exhibit bactericidal activity against E. coli, while the HA outer layer had no bactericidal activity. Both the bacterial antiadhesion activity and the bactericidal activity of the samples could be maintained even after storage in phosphate-buffered saline for up to 14 days. An in vitro MTT assay showed that the multilayers had no cytotoxicity to L929 cells, and HA molecules in the multilayers could improve the biocompatibility of the film.
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