Multilayered coating on titanium for controlled release of antimicrobial peptides for the prevention of implant-associated infections

Kazemzadeh-Narbat, Mehdi; Lai, Benjamin; Ding, Chuan‐Fan; Kizhakkedathu, Jayachandran N.; Hancock, Robert E. W.; Wang, Rizhi

doi:10.1016/j.biomaterials.2013.04.036

Cited by 311 publications

(228 citation statements)

References 49 publications

Supporting

Mentioning

224

Contrasting

Unclassified

Order By: Relevance

“…On the protocol in which only half of the medium was replaced, concentration gradient was lower, explaining the slower CHX release kinetics over the 14 days incubation. The observed behavior is in agreement with several studies showing that controlled drug release profiles usually reveal an initial burst release of short duration that is followed by a longer period of continuous but declining release [4,13,18,[42][43][44], and that the release pattern is dependent on the amount of antimicrobial agent adsorbed on biomaterials [13,44].…”

Section: Discussionsupporting

confidence: 91%

Anti-sessile bacterial and cytocompatibility properties of CHX-loaded nanohydroxyapatite

Barros

Grenho

Fernandes

et al. 2015

Colloids and Surfaces B: Biointerfaces

View full text Add to dashboard Cite

Nanohydroxyapatite possesses exceptional biocompatibility and bioactivity regarding bone cells and tis-sues, justifying its use as a coating material or as a bone substitute. Unfortunately, this feature may also encourage bacterial adhesion and biofilm formation. Surface functionalization with antimicrobials is a promising strategy to reduce the likelihood of bacterial infestation and colonization on medical devices. Chlorhexidine digluconate is a common and effective antimicrobial agent used for a wide range of medical applications. The purpose of this work was the development of a nanoHA biomaterial loaded with CHX to prevent surface bacterial accumulation and, simultaneously, with good cytocompatibility, for application in the medical field. CHX (5-1500 mg/L) was loaded onto nanoHA discs and the materials were evaluated for CHX adsorption and release profile, physic-chemical features, antibacterial activity against Escherichia coli, Staphylococcus aureus and Staphylococcus epidermidis, and cytocompatibility toward L929 fibroblasts. Results showed that the adsorption of CHX on nanoHA surface occurred by electrostatic inter-actions between the cationic group of CHX and the phosphate group of nanoHA. The release of CHX from CHX-loaded nanoHA showed a fast initial rate followed by a slower kinetics release, due to constraints caused by dilution and diffusion-limiting processes. NanoHA.50 to nanoHA.1500 showed strong anti-sessile activity, inhibiting bacterial adhesion and the biofilm formation. CHX-nanoHA caused a dose-and time-dependent inhibitory effect on the proliferation of fibroblasts for nanoHA.100 to nanoHA.1500. Cellular behavior on 2 nanoHA.5 and nanoHA.50 was similar to control. Therefore, CHX-loaded nanoHA surfaces appear as a promising alternative to prevention of devices-related infections.

show abstract

Section: Discussionsupporting

confidence: 91%

Anti-sessile bacterial and cytocompatibility properties of CHX-loaded nanohydroxyapatite

Barros

Grenho

Fernandes

et al. 2015

Colloids and Surfaces B: Biointerfaces

View full text Add to dashboard Cite

show abstract

“…Compared with other antimicrobial agents, such as antibiotics, antimicrobial peptides (AMPs) have a broad spectrum of activity and possess a low propensity for developing pathogen resistance (26). Antimicrobial peptides can be effectively immobilized on Ti substrates by the use of a phosphate lipid spray or cross-linking agent, e.g., sinalization or polyethylene glycol (PEG) (27,28). Despite several publications on the in vitro efficacy of AMPs (23)(24)(25), there are few studies demonstrating their efficacy in vivo (29).…”

mentioning

confidence: 99%

Effectiveness of Antimicrobial Peptide Immobilization for Preventing Perioperative Cornea Implant-Associated Bacterial Infection

Tan

Goh

Saraswathi

et al. 2014

Antimicrob Agents Chemother

View full text Add to dashboard Cite

Titanium (Ti) is a promising candidate biomaterial for an artificial corneal skirt. Antimicrobial peptide (AMP) immobilization may improve the bactericidal effect of the Ti substrate. In this study, we tested the bactericidal efficacy of a functionalized Ti surface in a rabbit keratitis model. A corneal stromal pocket was created by a femtosecond laser. The Ti films were then inserted into the pocket, and Staphylococcus aureus or Pseudomonas aeruginosa was inoculated into the pocket above the implant films. The corneas with Ti-AMP implants were compared with the corneas implanted with unprotected Ti by slit lamp observation and anterior segment optical coherence tomography (AS-OCT). Inflammatory responses were evaluated by bacterium counting, hematoxylin-eosin staining, and immunostaining. There was a lower incidence and a lesser extent of infection on rabbit corneas with Ti-AMP implants than on those with unprotected Ti implants. The bactericidal effect of AMP against S. aureus was comparable to that of postoperative prophylactic antibiotic treatment; hence, SESB2V AMP bound to the Ti implant provided functional activity in vivo, but its efficacy was greater against S. aureus than against P. aeruginosa. This work suggests that SESB2V AMP can be successfully functionalized in a rabbit keratitis model to prevent perioperative corneal infection.

show abstract

“…Conventional PPI prevention relies on systemic antibiotics, which possess several disadvantages: (i) it is difficult to achieve an effective local antibiotic concentration without risking systemic toxicity, (ii) therapy is ineffective once the adherent bacteria have formed a biofilm on the implant surface, and (iii) they increase the emergence of antibiotic-resistant bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), a common osteomyelitis-inducing pathogenic bacterium. Thus, many studies have focused on the development of novel medical biomaterials with antibacterial properties, such as metal implants, that prevent and/or treat implant-associated infection (3)(4)(5)(6).…”

mentioning

confidence: 99%

Antibacterial Properties of Magnesium In Vitro and in an In Vivo Model of Implant-Associated Methicillin-Resistant Staphylococcus aureus Infection

Liu

Zhai

et al. 2014

Antimicrob Agents Chemother

109

View full text Add to dashboard Cite

Periprosthetic infection remains a challenging clinical complication. We investigated the antibacterial properties of pure (99.9%) magnesium (Mg) in vitro and in an in vivo rat model of implant-related infection. Mg was highly effective against methicillin-resistant Staphylococcus aureus-induced osteomyelitis and improved new peri-implant bone formation. Bacterial icaA and agr RNAIII transcription levels were also assessed to characterize the mechanism underlying the antibacterial properties of the Mg implant.A rtificial metal implants are widely used to repair bone injury due to fractures, tumor resection, and other causes. However, periprosthetic infections (PPI) are a clinically challenging complication, as the biomaterial implant surfaces serve as substrates for bacterial adhesion, colonization, and biofilm formation (1, 2). Prolonged antimicrobial treatment, implant removal, and surgical revision are often necessary to cure PPI, which leads to increased patient morbidity and places a substantial health care burden on society. Conventional PPI prevention relies on systemic antibiotics, which possess several disadvantages: (i) it is difficult to achieve an effective local antibiotic concentration without risking systemic toxicity, (ii) therapy is ineffective once the adherent bacteria have formed a biofilm on the implant surface, and (iii) they increase the emergence of antibiotic-resistant bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), a common osteomyelitis-inducing pathogenic bacterium. Thus, many studies have focused on the development of novel medical biomaterials with antibacterial properties, such as metal implants, that prevent and/or treat implant-associated infection (3-6).Pure magnesium plates were first introduced as orthopedic implants in 1907. Since then, this biodegradable magnesiumbased metal and its alloy have been widely investigated for their utility as implant materials suitable for bone and cardiovascular applications due to their cytocompatibility and mechanical properties similar to those of natural bone (7-10). Previous investigations have found that the corrosion products of Mg degradation possess in vitro antibacterial function because they increase local alkalinity (11). These characteristics suggest that Mg-based metal could provide clinical utility as an orthopedic implant to prevent implant-associated infections. We investigated the in vitro and in vivo antibacterial properties of pure Mg (99.9%) against MRSA. Rat models of implant-related osteomyelitis (Sprague-Dawley rats) were implanted with pure Mg intramedullary nails. The efficacy of the nails for treating osteomyelitis and the amount of new peri-implant bone formation were evaluated. We also assessed bacterial icaA and agr RNAIII transcription to identify the mechanism underlying the antibacterial properties of pure Mg.The in vitro antibacterial efficiency of Mg and titanium (Ti) sample discs ( ϭ 15 mm) was analyzed using the spread plate method (12, 13) after coculturing with MRSA (ATCC 43300) for 6...

show abstract

Multilayered coating on titanium for controlled release of antimicrobial peptides for the prevention of implant-associated infections

Cited by 311 publications

References 49 publications

Anti-sessile bacterial and cytocompatibility properties of CHX-loaded nanohydroxyapatite

Anti-sessile bacterial and cytocompatibility properties of CHX-loaded nanohydroxyapatite

Effectiveness of Antimicrobial Peptide Immobilization for Preventing Perioperative Cornea Implant-Associated Bacterial Infection

Antibacterial Properties of Magnesium In Vitro and in an In Vivo Model of Implant-Associated Methicillin-Resistant Staphylococcus aureus Infection

Contact Info

Product

Resources

About