Qiaojie Wang

Antibacterial Surface Design of Titanium-Based Biomaterials for Enhanced Bacteria-Killing and Cell-Assisting Functions Against Periprosthetic Joint Infection.

Periprosthetic joint infection (PJI) is one of the formidable and recalcitrant complications after orthopedic surgery, and inhibiting biofilm formation on the implant surface is considered crucial to prophylaxis of PJI. However, it has recently been demonstrated that free-floating biofilm-like aggregates in the local body fluid and bacterial colonization on the implant and peri-implant tissues can coexist and are involved in the pathogenesis of PJI. An effective surface with both contact-killing and release-killing antimicrobial capabilities can potentially abate these concerns and minimize PJI caused by adherent/planktonic bacteria. Herein, Ag nanoparticles (NPs) are embedded in titania (TiO2) nanotubes by anodic oxidation and plasma immersion ion implantation (PIII) to form a contact-killing surface. Vancomycin is then incorporated into the nanotubes by vacuum extraction and lyophilization to produce the release-killing effect. A novel clinical PJI model system involving both in vitro and in vivo use of methicillin-resistant Staphylococcus aureus (MRSA) ST239 is established to systematically evaluate the antibacterial properties of the hybrid surface against planktonic and sessile bacteria. The vancomycin-loaded and Ag-implanted TiO2 nanotubular surface exhibits excellent antimicrobial and antibiofilm effects against planktonic/adherent bacteria without appreciable silver ion release. The fibroblasts/bacteria cocultures reveal that the surface can help fibroblasts to combat bacteria. We first utilize the nanoarchitecture of implant surface as a bridge between the inorganic bactericide (Ag NPs) and organic antibacterial agent (vancomycin) to achieve total victory in the battle of PJI. The combination of contact-killing and release-killing together with cell-assisting function also provides a novel and effective strategy to mitigate bacterial infection and biofilm formation on biomaterials and has large potential in orthopedic applications.

Intraoperatively-made cement-on-cement antibiotic-loaded articulating spacer for infected total knee arthroplasty

Cement articulating spacers have been used for the treatment of TKA infection. The disadvantages of commercially available pre-made mobile spacers include limitations in implant size and antibiotic dose, often allowing delivery of only a single antibiotic agent. Hand-made mobile spacers fail to provide a well-shaped and congruently articular surface and have difficulties in maintaining stability. We present a method of intraoperatively-made cement-on-cement antibiotic-loaded articulating spacer for infected total knee arthroplasty. A custom mold was made intraoperatively with bone cement and the standard posterior stabilized TKA provisional components which were of the same size as the original prosthesis. Fabrication of the spacers did not increase the overall surgical time. From 2004 to 2007, 17 infected total knee arthroplasties were treated with two-stage reimplantation. The average length of follow-up was 31 months. One patient required an above-knee amputation for persistent infection. A knee arthrodesis was performed in one case. Ten patients received reimplantation with Nexgen LCCK knee implants. Articulating spacers were retained in situ in five patients. This articulating spacer can help improve knee mobility and function during the interval between stages.

Sonication of Explanted Prosthesis Combined with Incubation in BD Bactec Bottles for Pathogen-Based Diagnosis of Prosthetic Joint Infection

ABSTRACT Prosthetic joint infection (PJI) is a rare but refractory complication of arthroplasty. Accurate identification of pathogens is a key step for successful treatment of PJI, which remains a challenge for clinicians and laboratory workers. We designed a combined culture method with sonication of implants and incubation in a BD Bactec system to improve the effectiveness of pathogen diagnosis in PJI. The aims of this study were to investigate the diagnostic accuracy of sonicate fluid cultures in the BD Bactec system and to compare the results with those of synovial fluid cultures in the BD Bactec system. The prosthetic components removed were sonicated in Ringers solution, and then sonicate fluid was incubated in Bactec bottles for 5 days. Synovial fluid was incubated in Bactec bottles for 5 days as a control. Synovial fluid cultures with Bactec bottles and sonicate fluid cultures with Bactec bottles showed sensitivities of 64% and 88%, respectively (P = 0.009), with specificities of 98% and 87% (P = 0.032), respectively. Sonicate fluid cultures with Bactec bottles were more sensitive than synovial fluid cultures with Bactec bottles regardless of whether antimicrobial agents were used within 14 days before surgery (81% versus 52%; P = 0.031) or not (93% versus 72%; P = 0.031). Sonication of explanted prostheses followed by incubation of the resulting sonicate fluid in Bactec bottles detected many more pathogens than did synovial fluid cultures with Bactec bottles. This method is also effective in cases with antibiotic treatment before surgery.

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.

Resurfacing arthroplasty for hip dysplasia: A prospective randomised study

In this prospective study a total of 80 consecutive Chinese patients with Crowe type I or II developmental dysplasia of the hip were randomly assigned for hip resurfacing arthroplasty (HRA) or total hip replacement (THR). Three patients assigned to HRA were converted to THR, and three HRA patients and two THR patients were lost to follow-up. This left a total of 34 patients (37 hips) who underwent HRA and 38 (39 hips) who underwent THR. The mean follow-up was 59.4 months (52 to 70) in the HRA group and 60.6 months (50 to 72) in the THR group. There was no failure of the prosthesis in either group. Flexion of the hip was significantly better after HRA, but there was no difference in the mean post-operative Harris hip scores between the groups. The mean size of the acetabular component in the HRA group was significantly larger than in the THR group (49.5 mm vs 46.1 mm, p = 0.001). There was no difference in the mean abduction angle of the acetabular component between the two groups. Although the patients in this series had risk factors for failure after HRA, such as low body weight, small femoral heads and dysplasia, the clinical results of resurfacing in those with Crowe type I or II hip dysplasia were satisfactory. Patients in the HRA group had a better range of movement, although neck-cup impingement was observed. However, more acetabular bone was sacrificed in HRA patients, and it is unclear whether this will have an adverse effect in the long term.

Comparison of 3 Routes of Administration of Tranexamic Acid on Primary Unilateral Total Knee Arthroplasty: A Prospective, Randomized, Controlled Study

BACKGROUND The mode of administration for tranexamic acid (TXA) to significantly reduce the decrease in hemoglobin (Hb), number of transfusions, relevant costs, and side effects in patients undergoing primary unilateral total knee arthroplasty (TKA) has not been resolved. METHODS A total of 560 patients undergoing primary unilateral TKA were randomized into 4 groups: intravenous group (140 patients receiving 2 doses of 20 mg/kg intravenous TXA), topical group (140 patients administered 3.0 g topical TXA), oral group (140 patients given 2 doses of 20 mg/kg oral TXA), and a control group (140 patients not given TXA). The primary outcomes included postoperative 48-hour Hb loss and drainage volume, number of transfusions, transfusion and TXA costs, and thromboembolic complications. Secondary outcomes were postoperative inpatient time and wound healing 3 weeks after TKA. RESULTS Baseline data among the 4 groups were similar. The 48-hour Hb loss and drainage volume in the intravenous, topical, and oral groups were significantly less (P < .05) than those in the control group, and the latter had significantly more transfusions and transfusion costs than the other 3 groups (P < .05). The TXA cost was lowest in the oral group compared with that in the topical and intravenous groups (P < .05). No differences in thromboembolic complications, postoperative inpatient time, or wound healing were observed among the groups. However, wound dehiscence and continuous wound discharge occurred in the topical group. CONCLUSION All the 3 modes of TXA administration significantly reduced postoperative Hb loss, the number of transfusions, and transfusion costs compared with those in the control group. No pulmonary embolism or infection was observed. Oral TXA is recommended because it provided a similar clinical benefit and resulted in the lowest TXA cost compared with the other 2 modes of TXA administration.

Staged reimplantation for the treatment of fungal peri-prosthetic joint infection following primary total knee arthroplasty.

BACKGROUND Fungal peri-prosthetic joint infections (PJI) are rare complication following total knee arthroplasty (TKA). There exists no established guidelines in the treatment of these infections and controversies are focused on the usefulness of antifungal-loaded cement spacers, the duration of systemic antifungal treatment and the ideal interval between implant removal and reimplantation. Therefore we ask if: (1) adding antifungal in cement space is a viable solution to manage fungal PJI; (2) there is no adverse effect adding antifungal medication in cement? HYPOTHESIS We hypothesized that fungal PJI following TKA could be managed successfully by 2-stage reimplantation strategy using antifungal-loaded cement spacer. PATIENTS AND METHODS Five cases of fungal PJI following total knee arthroplasty were treated in our institution between 2007 and 2013 using a 2-stage reimplantation strategy. The median elapsed time from primary arthroplasty to the diagnosis of infection was 7.4 months (range, 5-10 months). The infection was caused by Candida species in 4 cases and Pichia anomala in 1 case. Antibiotic- and antifungal-loaded articulating cement spacer was implanted during the interval between stages. Systemic antifungal agents were administered for at least 6 weeks after removal of prosthesis in all cases. The mean interval between removal and reimplantation was 6 months (range, 3-9 months). RESULTS At a mean follow-up of 41.6 months (range, 24-65 months) after reimplantation, no patient had recurrent infection or revision due to any other reasons. The mean global IKS score improved from 58.4 (range, 37-96 points) preoperatively to 152.4 (range, 136-169 points) at final follow-up. The average range of motion of the knee for flexion improved from 63° (range, 10-110°) preoperatively to 98° (range, 80-120°) at final follow-up. CONCLUSIONS Fungal PJI following TKA can be successfully treated by a staged reimplantation strategy. Antibiotic- and antifungal-loaded cement spacer implanted during interval period between stages may be an effective adjunct to therapy. Effective antifungal therapy is crucial to a successful result without adverse effect. LEVEL OF EVIDENCE IV: retrospective or historical series.

Cementless total hip arthroplasty for the treatment of advanced tuberculosis of the hip.

The question of whether a total hip arthroplasty (THA) should be attempted in a patient with a current or previous tuberculosis infection continues to cause controversy. The goal of this study was to evaluate the clinical result of cementless THA for the treatment of advanced tuberculosis of the hip. Eight patients with advanced tuberculosis of the hip treated by cementless THA were retrospectively analyzed. None of the patients had draining sinus preoperatively. For patients with a confirmed preoperative diagnosis of tuberculosis and elevated C-reactive protein and erythrocyte sedimentation rate, antituberculous medication was prescribed for at least 2 weeks preoperatively. Inflamed soft tissues and destroyed bones were completely curetted out intraoperatively. All 8 patients received 1-stage cementless THA after thorough debridement. Antituberculous medications were prescribed for all patients for the first 6 months postoperatively. No patient experienced wound-healing complications. Mean Harris Hip Score was 35 (range, 30-43) preoperatively and 91 (range, 87-95) at last follow-up. At an average 46-month follow-up (range, 34-59 months), no reactivation of tuberculosis was detected. All 8 patients revealed stability by bone ingrowth on both the socket and femoral stem. Cementless THA is a safe and effective procedure for advanced tuberculosis of the hip. With thorough debridement followed by a complete course of antituberculous chemotherapy, active tuberculous infection should not be considered a contraindication for THA.

A lithium-containing nanoporous coating on entangled titanium scaffold can enhance osseointegration through Wnt/β-catenin pathway

An entangled titanium wire porous (ETP) scaffold shows similar mechanical properties of cancellous bone and is a promising bone repair material. However, the ETP scaffolds inert biocompatibility and poor osteogenic ability limit its clinical application. In this study, a Li-containing nanoporous coating was added on ETP by micro-arc oxidation (MAO). The SEM results indicated that a hierarchical and compact coating was formed on the Li-MAO-ETP scaffold. In vitro cell tests showed improved osteoblast morphology, adhesion, and viability in the Li-MAO-ETP group. Moreover, the Li-MAO-ETP scaffold exhibited improved osteogenic differentiation properties by activating the Wnt/β-catenin signal pathway based on the western blotting and RT-PCR results. The push-out test, sequential fluochrome labeling, and toluidine staining demonstrated that the Li-MAO-ETP scaffold contained improved osteogenic ability in vivo. The in vitro and in vivo experiments showed that the Li incorporated entangled porous titanium could be a suitable biomaterial for bone defect repair.