Hui Qin

A Systematic Review and Meta-Analysis of Antibiotic-Impregnated Bone Cement Use in Primary Total Hip or Knee Arthroplasty

Background Antibiotic-impregnated bone cement (AIBC) has been widely used for the treatment of infected revision arthroplasty, but its routine use in primary total joint arthroplasty (TJA) remains considerably controversial. With this meta-analysis of published randomized controlled trials, we intended to assess the antimicrobial efficacy and safety of AIBC for its prophylactic use in primary TJA. Methods A literature search was performed in MEDLINE, Embase, CBMdisc and the Cochrane Library until June, 2013. The studies were divided into two sub-groups according to the type of the control group. Outcomes of interest included postoperative infection rates, radiographic outcomes and clinical joint score. Study quality was evaluated using the Jadad scale (five points). Results In total, eight studies were included, with a sample size of 6,381 arthroplasties. The overall pooled data demonstrated that, compared with the control (plain cement or systemic antibiotic), AIBC did not reveal an advantage in decreasing the rate of superficial infection (relative risk [RR] = 1.47; 95% CI, 1.13–1.91; P=0.004), while there were significant differences in deep infection rate between the AIBC and control group (RR = 0.41; 95% CI, 0.17–0.97; P=0.04). For the analysis of gentamicin and cefuroxime subgroups, the gentamicin was superior to the cefuroxime in reducing deep infection rate (P=0.0005 versus P= 0.10). However, no significant differences were found in their radiographic outcomes and clinical joint score. Conclusion This meta-analysis had proven that the prophylactic use of AIBC could lower the deep infection rate in primary TJA, while AIBC did not show an improvement in reducing the superficial infection rate compared with the control. More sufficiently powered studies would be required to further evaluate the efficacy and safety of AIBC for primary TJA.

Silver nanoparticles promote osteogenic differentiation of human urine-derived stem cells at noncytotoxic concentrations

In tissue engineering, urine-derived stem cells are ideal seed cells and silver nanoparticles (AgNPs) are perfect antimicrobial agents. Due to a distinct lack of information on the effects of AgNPs on urine-derived stem cells, a study was conducted to evaluate the effects of silver ions and AgNPs upon the cytotoxicity and osteogenic differentiation of urine-derived stem cells. Initially, AgNPs or AgNO3 were exposed to urine-derived stem cells for 24 hours. Cytotoxicity was measured using the Cell Counting kit-8 (CCK-8) test. The effects of AgNPs or AgNO3 at the maximum safety concentration determined by the CCK-8 test on osteogenic differentiation of urine-derived stem cells were assessed by alkaline phosphatase activity, Alizarin Red S staining, and the quantitative reverse transcription polymerase chain reaction. Lastly, the effects of AgNPs or AgNO3 on “urine-derived stem cell actin cytoskeleton organization” and RhoA activity were assessed by rhodamine-phalloidin staining and Western blotting. Concentration-dependent toxicity was observed starting at an AgNO3 concentration of 2 μg/mL and at an AgNP concentration of 4 μg/mL. At these concentrations, AgNPs were observed to promote osteogenic differentiation of urine-derived stem cells, induce actin polymerization and increase cytoskeletal tension, and activate RhoA; AgNO3 had no such effects. In conclusion, AgNPs can promote osteogenic differentiation of urine-derived stem cells at a suitable concentration, independently of silver ions, and are suitable for incorporation into tissue-engineered scaffolds that utilize urine-derived stem cells as seed cells.

Antimicrobial and osteogenic properties of silver-ion-implanted stainless steel.

Prevention of implant loosening and infection is crucial to orthopedic and dental surgeries. In this work, the surface of stainless steel (SS) was modified by silver-sourced plasma immersion ion implantation (Ag-PIII). Metallic silver nanoparticles with various diameters and distributions were fabricated on the SS surfaces after treatment with Ag-PIII for 0.5 and 1.5 h, respectively. The osteogenic activity and antimicrobial properties of SS before and after Ag-PIII treatment were evaluated using in vitro and in vivo tests. The results demonstrated that Ag-PIII treatment not only promoted the antibacterial activity of SS but also enhanced the osteogenic differentiation of human bone marrow stromal cells.

Calcium Plasma Implanted Titanium Surface with Hierarchical Microstructure for Improving the Bone Formation

Introducing hierarchical microstructure and bioactive trace elements simultaneously onto the surface of titanium implant is a very effective way to improve the osseointegration between bone and implant. In this work, hierarchical topography was prepared on Ti surface via acid etching and sandblasting (SLA) to form micropits and microcavities then underwent Ca plasma immersion ion implantation (Ca-PIII) process. The surface wettability and roughness did not change obviously before and after Ca-PIII process. The in vitro evaluations including cell adhesion, activity, alkaline phosphatase (ALP), osteogenic genes (Runx2, OSX, ALP, BSP, Col1a1, OPN, and OC), and protein (BSP, Col1a1, OPN, and OC) expressions revealed that the introduction of Ca ions onto the surface of SLA-treated Ti can promote greater osteoblasts adhesion, spread and proliferation, which in return further accelerated the maturation and mineralization of osteoblasts. More importantly, in vivo evaluations including Micro-CT evaluation, histological observations, push-out test, sequential fluorescent labeling and histological observations verified that Ca-SLA-treated Ti implants could efficiently promote new bone formation in early times. These promising results suggest that Ca-SLA-treated Ti has the potential for future application in orthopedic field.

Balancing the Osteogenic and Antibacterial Properties of Titanium by Codoping of Mg and Ag: An in Vitro and in Vivo Study

To simultaneously enhance the osteogenic and antibacterial properties of titanium, we introduced magnesium (Mg), silver (Ag), or both by using the plasma immersion ion implantation (PIII) technique, producing three PIII sample groups, namely, Mg-doped titanium (Mg-PIII), Ag-doped titanium (Ag-PIII), and Mg and Ag codoped titanium (Mg/Ag-PIII). The in vitro antibacterial efficacy of Mg/Ag-PIII group was about 7-10% higher than that of Ag-PIII. In vitro and in vivo results demonstrated that osteogenic property of Mg/Ag PIII group was better than that of Ag-PIII or Mg-PIII. It was believed that the galvanic effects between Mg and Ag NPs played a key role in facilitating the release of Mg but reducing the release of silver, answering for the selective performances of the Mg/Ag-PIII group over bacterial and mammalian cells. This study demonstrated that the integration of multiple functional elements could be realized by the dual-source PIII technique, and in this case, the antibacterial properties and osteogenic property of titanium could be balanced.

Silver-nanoparticles-modified biomaterial surface resistant to staphylococcus: new insight into the antimicrobial action of silver.

Titanium implants are widely used clinically, but postoperative implant infection remains a potential severe complication. The purpose of this study was to investigate the antibacterial activity of nano-silver(Ag)-functionalized Ti surfaces against epidemic Staphylococcus from the perspective of the regulation of biofilm-related genes and based on a bacteria-cell co-culture study. To achieve this goal, two representative epidemic Staphylococcus strains, Staphylococcus epidermidis (S. epidermidis, RP62A) and Staphylococcus aureus (S. aureus, USA 300), were used, and it was found that an Ag-nanoparticle-modified Ti surface could regulate the expression levels of biofilm-related genes (icaA and icaR for S. epidermidis; fnbA and fnbB for S. aureus) to inhibit bacterial adhesion and biofilm formation. Moreover, a novel bacteria-fibroblast co-culture study revealed that the incorporation of Ag nanoparticles on such a surface can help mammalian cells to survive, adhere and spread more successfully than Staphylococcus. Therefore, the modified surface was demonstrated to possess a good anti-infective capability against both sessile bacteria and planktonic bacteria through synergy between the effects of Ag nanoparticles and ion release. This work provides new insight into the antimicrobial action and mechanism of Ag-nanoparticle-functionalized Ti surfaces with bacteria-killing and cell-assisting capabilities and paves the way towards better satisfying the clinical needs.

Anti-biofilm properties of magnesium metal via alkaline pH

Prevention of implant-associated infection (IAI) by inhibiting biofilm formation on implants is crucial to orthopedic surgery. In this work, the anti-biofilm activity of magnesium (Mg) is assessed using Pseudomonas aeruginosa (P. aeruginosa) and Staphylococcus epidermidis (S. epidermidis), two biofilm producing strains, in vitro, and using S. epidermidis in vivo. The effects of high Mg2+ concentration and alkaline pH on biofilm are evaluated in two separate experiments in vitro. Mg shows biofilm resistance proportional to the degradation of Mg in vitro, which is better than that of the corresponding alkaline pH, and high Mg2+ concentration has no such effect. Microbiological cultures and histological results demonstrate the ability of Mg against bacterial infection to reduce the risk of IAI in vivo. The results demonstrate that Mg prevents bacteria biofilm formation by high alkalinity at its surface rather than by high Mg2+ concentration, thus providing a promising new strategy for combating IAI.

The Potential Role of Increasing the Release of Mouse β- Defensin-14 in the Treatment of Osteomyelitis in Mice: A Primary Study

Mammalian β-defensins are small cationic peptides that have been implicated in mediating innate immune defenses against microbial infection. Mouse β-defensin-14 (MBD-14), based on structural and functional similarities, appears to be an ortholog of human β-defensin-3 (HBD-3). Previous studies identified signaling pathway p38 mitogen-activated protein kinase (MAPK) that contributed to the expression of MBD-14 in mouse osteoblasts upon contacted with methicillin-resistance Staphylococcus aureus (MRSA) supernatant, which provided a theoretical basis as a promising therapeutic target in the treatment of intramedullary infection with MRSA in vivo. In this study, the medullary cavities of tibiae were contaminated with MRSA 103 colony forming units and different doses of p38 MAPK agonists anisomycin were followed as group III or IV in 30 mice. Fifteen animals that received phosphate- buffered saline served as group II and 15 mice were not contaminated with MRSA and received phosphate-buffered saline served as controls (group I). Follow-up was 7 days. In day 1, day 4 and day 7 postoperatively, infection was evaluated by blood routine, microbiological and histological analyses after sacrifice. All animals of group II developed microbiological and histological signs of infection. Histological signs of infection, white blood counts and cultures of group III and IV showed significantly reduced bacterial growth compared to cultures of group II. Simultaneously, different doses of anisomycin significantly induced the expression of osteoblast-associated genes, including alkaline phosphatase, osteocalcin and collagen type I. In addition, the expression of HBD-3 in human interfacial membranes around infected periprosthetic joint by staphylococcus contaminated was evaluated, and the expression pattern changed with significant induction of HBD-3 in infected periprosthetic joint compared with aseptic loosening under inflammatory conditions. Our primary study indicated that the potential antibacterial role of increased MBD-14 in the osteomyelitis mouse model.

In vitro and in vivo responses of macrophages to magnesium-doped titanium

Modulating immune response to biomaterials through changing macrophage polarization has been proven to be a promising strategy to elicit beneficial outcomes in tissue repair. The objective of this study was to evaluate the response of macrophage polarization to titanium doped with magnesium (0.1~0.35%), which was prepared through the magnesium plasma immersion ion implantation (Mg PIII) technique. The M1/M2 polarization profile of macrophages was investigated using a murine cell line RAW 264.7 in vitro and a murine air pouch model in vivo. Our results demonstrated that the Mg PIII-treated titanium induced a higher percentage of M2 macrophages and higher concentrations of the anti-inflammatory cytokines interleukin (IL)-4 and IL-10. Genes encoding two growth factors, bone morphogenetic protein 2 (BMP2) and vascular endothelial growth factor (VEGF) were up-regulated, thus indicating the ability of the M2 phenotype to promote wound healing. The nuclear factor κB (NF-κB) signalling pathway was down-regulated. In vivo the Mg PIII -treated titanium elicited a similar effect on macrophage polarization and induced thinner fibrous capsule formation and a decrease in infiltrated cells. These results indicate that Mg PIII treatment has the immunomodulatory potential to elicit the pro-healing M2-polarized macrophage phenotype, thus providing new insight into the development of immunomodulatory biomaterials.

The in vitro and in vivo performance of a strontium-containing coating on the low-modulus Ti35Nb2Ta3Zr alloy formed by micro-arc oxidation

The β-titanium alloy is thought to be a promising alloy using as orthopedic or dental implants owing to its characteristics, which contains low elastic modulus, high corrosion resistance and well biocompatibility. Our previous study has reported that a new β-titanium alloy Ti35Nb2Ta3Zr showed low modulus close to human bone, equal tissue compatibility to a traditional implant alloy Ti6Al4V. In this study, micro-arc oxidation (MAO) was applied on the Ti35Nb2Ta3Zr alloy to enhance its surface characteristics and biocompatibility and osseointegration ability. Two different coatings were formed, TiO2 doped with calcium–phosphate coating (Ca–P) and calcium–phosphate–strontium coating (Ca–P–Sr). Then we evaluated the effects of the MAO coatings on the Ti35Nb2Ta3Zr alloy through in vitro and in vivo tests. As to the characteristics of the coatings, the morphology, chemical composition, surface roughness and contact angle of MAO coatings were tested by scanning electron microscopy, energy dispersive spectroscopy, atomic force microscopy, and video contact-angle measurement system respectively. Besides, we performed MTT assay, ALP test and cell morphology-adhesion test on materials to evaluate the MAOed coating materials’ biocompatibility in vitro. The in vivo experiment was performed through rabbit model. Alloys were implanted into rabbits’ femur shafts, then we performed micro-CT, histological and sequential fluorescent labeling analysis to evaluate implants’ osseointegration ability in vivo. Finally, the Ca–P specimens and Ca–P–Sr specimens exhibited a significant enhancement in surface roughness, hydrophilicity, cell proliferation, cell adhesion. More new bone was found around the Ca–P–Sr coated alloy than Ca–P coated alloy and Ti35Nb2Ta3Zr alloy. In conclusion, the MAO treatment improved in vitro and in vivo performance of Ti35Nb2Ta3Zr alloy. The Ca–P–Sr coating may be a promising modified surface formed by MAO for the novel β-titanium alloy Ti35Nb2Ta3Zr.