Efficacy of Commercially Available Irrigation Solutions on Removal of Staphylococcus Aureus and Biofilm From Porous Titanium Implants: An In Vitro Study.

BACKGROUND: Periprosthetic joint infection remains a major problem. The bactericidal efficacy of commercial irrigation solutions for the treatment of infection is not well established in the presence of porous titanium (Ti) implants. This study compared the in vitro efficacy of five irrigation solutions on infected three-dimensional-printed porous Ti discs. METHODS: Titanium discs (2 × 4 mm, 400, 700, and 1,000 µm) were infected with S. aureus (1 × 106 colony-forming unit/mL) and incubated for 3 hours or 3 days to create acute or chronic infection with biofilm. Discs were irrigated with saline, antibiotic, or antiseptic solutions, then repeatedly sonicated. Sonicates were cultured for bacterial quantification. Statistical analyses were performed using one-way analysis of variance (ANOVA), followed by Tukey-Kramer post hoc testing (P < .05 significance). Biofilms were visualized by scanning electron microscopy. RESULTS: Saline irrigation was ineffective in both groups. In acute infections with 400 µm pores, differences were found with saline versus solution #3 (P = .015) and #4 (P = .015). Solution #4 had the lowest bacterial counts for all pore sizes. For biofilm, irrigation with saline, solutions #1, #2, and #3 inadequately cleared bacteria in all pore sizes. Lower remaining concentrations were observed in #4 with 400µm pores compared to saline (P = .06) and #2 (P = .039). The scanning electron microscopy showed a reduction of biofilm in samples washed with #4. CONCLUSIONS: Irrigation of infected porous Ti discs with saline, solutions #1 and #2 failed to reduce the bacterial load. The 400 µm discs consistently had more bacteria despite irrigation, highlighting the difficulty of removing bacteria from small pores. Solutions #3 and #4 reduced bacteria acutely, but only #4 demonstrated efficacy in clearing biofilm compared to saline. These results should be considered when treating periprosthetic joint infection in the presence of porous components and the potential presence of biofilm.

Effects of Vancomycin/Tobramycin-Doped Ceramic Composite (Polyvinyl Alcohol Composite-Vancomycin/Tobramycin-Polymeric Dicalcium Phosphate Dihydrate) in a Rat Femur Model Implanted With Contaminated Porous Titanium Cylinders.

BACKGROUND: Periprosthetic joint infection (PJI) remains common and problematic. We hypothesized that using a bioceramic that provided rapid release of the antibiotics (vancomycin [VAN] or VAN and tobramycin [VAN and TOB]) from a polyvinyl-alcohol-composite (PVA) combined with a delayed and sustained antibiotic release from polymeric-dicalcium-phosphate-dihydrate (PDCPD) ceramic would inhibit S. aureus-associated implant infections. METHODS: A total of 50 male Sprague Dawley rats were randomly divided into 5 groups-I: negative control; II: bacteria only; III: bacteria + saline wash; IV: bacteria + PVA-VAN-PDCPD, and V: bacteria + PVA-VAN-TOB-PDCPD. A porous titanium (Ti) implant was press-fit into the rat knee. S. aureus-containing broth was added into the joint space creating a PJI. After 1 week, the joints from groups III to V were washed with saline and the fluid collected for bacterial quantification. This was followed by saline irrigation treatment (groups III to V) and application of the antibiotic-loaded PVA-PDCPD bioceramic (groups IV and V). On day 21, joint fluid was collected, and the implants harvested for bacterial quantification. RESULTS: No bacteria were isolated from the negative control (group I). The positive control (group II) was positive on both days 7 and 21. Bacteria were still present on day 21 in the fluid and implant in group III. Groups (IV and V) showed a decrease in the bacterial burden in the fluid and implant on day 21. There were significant differences in bacteria levels in the collected wash fluid and on the implant at day 21 between the saline wash (group III) and treatment groups (IV and V). CONCLUSIONS: In this animal model of acute periprosthetic infection, treatment with PVA-VAN-PDCPD and PVA-VAN/TOB-PDCPD reduced bacterial load in the infected joint and the infected Ti implant. Application of PVA-VAN-PDCPD and/or PVA-VAN/TOB-PDCPD after saline irrigation could be used as an addition to the treatment of PJI.

Practice and performance of domestic waste source segregation in Chinese universities: A case study in Shanghai.

The importance and urgency of domestic solid waste (DSW) source segregation in universities is self-evident. Although many universities have carried out waste management, however, a comprehensive summary for successful implementation work of DSW segregation is lacking. This study summarizes the mechanism of DSW segregation in Chinese university based on questionnaire survey, on-site inquiry and sampling analysis in a comprehensive university in Shanghai. Questionnaire survey show that it is critical for encouraging students to participate in waste segregation to build convenient segregation facilities and humanized segregation reward and punishment method. The strengthened publicity and education due to the advantages in environmental discipline, easy-operating waste dumping site/facility as well as personalized solutions for different functional areas (teaching building) were considerably important strategies for implementing efficient waste segregation. The recyclables that were collected by intelligent recycling device and mobile recycling enterprise were dominated by paper, and the amounts increased dramatically during the graduation season. Therefore, the university correspondingly increased the collection frequencies of waste and the number of segregation guiders in the period to decrease the potential risk of fire safety. The study could provide a valuable reference for efficient implementation of waste segregation on university/college in China.

Mark Coventry Award: Efficacy of Saline Wash Plus Antibiotics Doped Polyvinyl Alcohol (PVA) Composite (PVA-VAN/TOB-P) in a Mouse Pouch Infection Model.

BACKGROUND: The efficacy of saline irrigation for treatment of periprosthetic infection (PJI) is limited by the presence of contaminated medical devices. This study evaluated treatment efficacy of locally placed polyvinyl alcohol (PVA)/bioceramic composite doped with vancomycin (PVA-VAN-P) or vancomycin and tobramycin (PVA-VAN/TOB-P) after saline irrigation in a mouse pouch infection model. METHODS: Sutures were implanted into air pouches of BALB/cJ mice, then inoculated with Staphylococcus aureus. Mice were randomized into 6 groups (n = 6 each): (1) no bacteria; (2) bacteria without saline wash; (3) saline wash only; (4) saline wash + PVA-P; (5) saline wash + PVA-VAN-P, and (6) saline wash + PVA-VAN/TOB-P. After 7 days, pouches were washed with saline alone or with additional injection of 0.2 mL of the composites. Sacrifice occurred 14 days after the washout. Histology was performed on the pouch tissues and bacteria cultures on the washout fluid. RESULTS: Bacterial culture (optical density) showed that infection persisted after saline irrigation (0.10 ± 0.14) but was effectively eradicated by the addition of PVA-VAN-P (0.05 ± 0.09) and PVA-VAN/TOB-P (0.002 ± 0.003, P < .05). These effects were confirmed by histology. Importantly, no residues of the PVA-P were detected in either the pouch washouts or pouch tissues. CONCLUSION: PJI is common and problematic, and few innovations have changed clinical practice and/or outcome. Our data confirmed that the effect of saline irrigation was very limited in the presence of contaminated sutures. PVA-VAN/TOB-P was biodegradable, biocompatible, and effective in eradicating bacterial retention after saline irrigation. Application of PVA-VAN/TOB-P after saline irrigation could be an option for treatment of PJI and should be evaluated in future PJI animal models.

Does Suture Type Influence Bacterial Retention and Biofilm Formation After Irrigation in a Mouse Model?

BACKGROUND: Irrigation and débridement are frequently utilized in the management of surgical infections, but even with aggressive débridement, it is difficult to remove all the suture material from the tissues and retained suture material may harbor bacteria and/or biofilm. The degree to which barbed or braided sutures may differentially influence the risk of infection has not been defined in a well-controlled animal model. QUESTIONS/PURPOSES: We compared braided and barbed monofilament sutures after irrigation of an infected mouse air pouch model to determine whether the suture type influenced the effectiveness of the irrigation. After irrigation of infected pouches, sutures were compared for (1) bacterial adherence and bacterial retention; (2) qualitative and quantitative pouch thickness and cellular density; and (3) quantitative biofilm formation. METHODS: Soft tissue air pouches were created on the backs of 60 female, mature 10-week-old BALB/cJ mice by sequentially introducing air into the subcutaneous tissue and allowing the pouch to mature. The pouches were inoculated with Staphylococcus aureus and braided or barbed monofilament sutures were implanted. Pouch irrigation was performed Day 7 after suture implantation. Suture segments were collected before and after irrigation. After euthanasia on Day 14, pouch tissues with residual suture segments were collected for analysis: microbiologic analysis done using optical density as a measure of the concentration of bacteria in the culture (the larger concentration indicates higher number of bacteria) and histologic evaluation of the pouch tissues were semiquantitative, whereas environmental scanning electron microscopy (ESEM) and confocal analyses of the biofilm and bacteria on the sutures were qualitative. RESULTS: Histologic evaluation of pouch tissue showed all groups had inflammatory responses. Quantitatively microbiology showed no difference in bacterial number calculated from the optical density (OD) values between the two suture materials at any time point in the irrigation group. In the no-irrigation group, for the Day 7 time point, mean (± SD) OD was greater in the barbed than the OD in the braided sutures (0.52 ± 0.12 versus 0.37 ± 0.16, mean difference 0.43 [95% confidence interval, 0.08-0.13]; p = 0.007). Qualitatively, ESEM showed more bacterial retention by braided sutures before and after irrigation. Confocal imaging of the sutures demonstrated penetration of biofilm into the interstices of braided sutures and less adhesion in barbed monofilament sutures. The quantification of the biomass showed no differences between groups at all time points (before-irrigation biomass was 11.2 ± 9.3 for braided versus 5.2 ± 4.7 for barbed sutures, p = 0.196; and after-irrigation biomass was 7.2 ± 7.5 for braided versus 3.3 ± 4.3 for barbed suture, p = 0.259). CONCLUSIONS: All sutures can retain bacteria and biofilm, but it is rarely possible to remove all suture material at the time of irrigation to treat infection. After an irrigation procedure, qualitatively braided sutures appeared to harbor more bacteria and to retain more biofilm than barbed monofilaments. CLINICAL RELEVANCE: When saline irrigation was used to simulate infection treatment in an infected mouse air pouch model, bacteria/biofilm was not completely eliminated from either braided or barbed monofilament sutures. The irrigation appeared to clear more bacteria and biofilm from the monofilament despite having barbs. Unfortunately, current technologies do not allow direct quantitative comparisons of biofilm retention. Clinicians should be aware that in the face of infection, any retained sutures may harbor bacteria despite irrigation.

Defect Detection of Aluminium Plates Based on Near-Field Enhancement of Lamb Waves Generated Using an Electromagnetic Acoustic Tranducer.

Ultrasonic testing is an important means to detect defacing defects, such as scratches and cracks, but when the size of these defects is smaller than the wavelength of ultrasonic waves, it is difficult to detect them using traditional methods like the pulse-echo method and broadband ultrasound attenuation method for the diffraction of ultrasonic waves at the defects. Based on the non-contact characteristic of electromagnetic acoustic transducers (EMATs), a transducer for scanning inspection was developed in this paper. The transducer was utilized to detect and measure the depth of the defacing defects on an aluminium plate based on the near-field enhancement of ultrasonic Lamb waves. The results show that the amplitude of the S0 Lamb wave experiences a large enhancement when the transducer is passed over the scratch defects and the enhancement has a clearly positive correlation with the depth of the scratch defects. When the depth increases from 0.1 mm to 0.9 mm, the amplitude of S0 Lamb waves increases from 1.13 times to 2.27 times the S0 Lamb waves received on the aluminium plate without defects. The new method can be utilized to detect the defacing defects on the aluminium plate and get better detection effects than the traditional methods without analyzing the relatively small reflection waves.

Fast Measurement of Magnetostriction Coefficients for Silicon Steel Strips Using Magnetostriction-Based EMAT.

Strain gauges and optical methods are commonly used to measure the magnetostriction coefficient of a sample. All these methods require a specific size sample and can only realize offline measurement, which is time-consuming. Therefore, we propose a new method using a magnetostriction-based electromagnetic acoustic transducer (EMAT) to measure the magnetostriction coefficient. The amplitude of the ultrasonic waves generated by the EMAT is applied to characterize the magnetostriction coefficient of a sample. A nonlinear magnetostriction finite element model is established, and the simulation results show that the amplitude of the ultrasonic wave generated by the magnetostriction-based EMAT is proportional to the magnetostriction coefficient of the material. Experiments are carried out on silicon steel strips with different silicon contents. The results show that the method can effectively measure their relative magnetostriction coefficients. Furthermore, the structure of the magnetostriction-based EMAT is optimized to maximize efficiency. The excitation and receiving transducers reach their maximum efficiency when the static magnetic flux densities are 3.5 mT and 6.8 mT, respectively. Moreover, the relative error caused by the vibration reaches the minimal size when the lift-off of the receiving coil is set to 3 mm around. This method is fast and can be applied to online measurement.

Prognostic significance of VEGF expression in osteosarcoma: a meta-analysis.

Vascular endothelial growth factor (VEGF) is considered as a prime mediator of angiogenesis and has been implicated in carcinogenesis and metastasis. Various studies examined the relationship between VEGF overexpression with the clinical outcome in patients with osteosarcoma but yielded conflicting results. Electronic databases updated to April 2013 were searched to find relevant studies. A meta-analysis was conducted with eligible studies which quantitatively evaluated the relationship between VEGF overexpression and survival of patients with osteosarcoma. Survival data were aggregated and quantitatively analyzed. We performed a meta-analysis of eight studies that evaluated the correlation between VEGF overexpression and survival in patients with osteosarcoma. Combined hazard ratios suggested that VEGF overexpression had an unfavorable impact on overall survival (hazard ratio (HR) = 1.75, 95% confidence interval (CI): 1.21-2.28) in patients with osteosarcoma for overall populations, 2.37 (1.35-3.39) in Asian studies but not in non-Asian studies (HR = 1.51, 95% CI: 0.89-2.14). No significant heterogeneity was observed among all studies. VEGF overexpression indicates a poor prognosis for patients with osteosarcoma. However, the prognostic value of VEGF on survival in osteosarcoma patients still needs further large-scale prospective trials to be clarified.

Stro-1-positive BMSCs predict postoperative periprosthetic bone mineral density outcomes in uncemented total hip arthroplasty patients.

BACKGROUND: Bone marrow cell profiles are variable after total hip arthroplasty (THA), including variable levels of Stro-1+ and bone morphogenetic protein receptor (BMPRs)+ cells. We investigated the impact of bone marrow cell profiles on changes in periprosthetic bone mineral density (BMD) in uncemented THA patients. MATERIAL AND METHODS: Bone marrow aspirates were collected from the metaphyseal region of discarded femoral heads from 24 consecutive THA patients (12 men and 12 women; mean age 66.7 ± 11.0 years; range 52-87 years) treated from March 2009 to March 2011 at a single facility. Perioperative proportions of Stro-1+ and BMPR+ cells in femoral heads were assessed by flow cytometry. Follow-up examined the proximal femur Gruen zones R1 and R7 at 1 week and at 3, 6, and 12 months after THA, using dual-energy X-ray absorptiometry. Associations between BMD loss and age, gender, BMPRs+, and Stro-1+ were analyzed. RESULTS: At 3 months, R1 and R7 BMD decreased by 4.4% and 6.4%, respectively (P<0.05). At 12 months, the overall BMD decreases in R1 and R7 were 10.2% and 1%, respectively (P<0.05). Higher Stro-1+ cells proportion predicted R7 BMD increases at all time points (P<0.05) and R1 BMD increases at 6 and 12 months (P<0.05). BMPR1a+ proportion was associated with BMD increases at 6 months in the R1 region. BMPR2+ was not significantly associated with BMD (P>0.05). CONCLUSIONS: Elevated Stro-1+ bone marrow cell profile may be a useful prognostic indicator for uncemented THA patients.

Mitigative effect of erythromycin on PMMA challenged preosteoblastic MC3T3-E1 cells.

BACKGROUND: Aseptic loosening (AL) is a major complication of total joint replacement. Recent approaches to limiting AL have focused on inhibiting periprosthetic inflammation and osteoclastogenesis. QUESTIONS/PURPOSES: The purpose of this study was to determine the effects of erythromycin (EM) on polymethylmethacrylate (PMMA) particle-challenged MC3T3 osteoblast precursor cells. MetHODS: MC3T3 cells were pretreated with EM (0-10 µg/mL) and then stimulated with PMMA (1 mg/mL). Cell viability was evaluated by both a lactate dehydrogenase (LDH) release assay and cell counts. Cell differentiation was determined by activity of alkaline phosphatase (ALP). Gene expression was measured via real-time quantitative RT-PCR. RESULTS: We found that exposure to PMMA particles reduced cellular viability and osteogenetic potential in MC3T3 cell line. EM treatment mitigated the effects of PMMA particles on the proliferation, viability and differentiation of MC3T3 cells. PMMA decreased the gene expression of Runx2, osterix and osteocalcin, which can be partially restored by EM treatment. Furthermore, EM suppressed PMMA- induced increase of NF-κB gene expression. CONCLUSIONS: These data demonstrate that EM mitigates the effects of PMMA on MC3T3 cell viability and differentiation, in part through downregulation of NF-κB pathway. EM appeared to represent an anabolic agent on MC3T3 cells challenged with PMMA particles.

Effect of Commercially Available Wound Irrigation Solutions on Uninfected Host Tissue in a Murine Model.

Background: Commercially available irrigation solutions are used to reduce bacterial contamination and prevent surgical site infections. However, the effect of these solutions on the healing capacity of tissue has not been well-established. The purpose of this study was to investigate the effects of 5 commercially available irrigation solutions on host tissue in a murine model. Methods: There were 5 treatment groups: bacitracin, Clorpactin, Irrisept, Prontosan, Bactisure, and normal saline control. The irrigation solutions were applied to the wound for 30 seconds or 1 minute, as per the manufacturer's instructions, and then washed with normal saline. Mice were sacrificed at 3 days and 10 days. The tissue was examined histologically for inflammation, edema, granulation tissue formation, and re-epithelialization. Granulation tissue formation and re-epithelialization were surrogates for effective wound healing. Results: All of the irrigation solutions had negative effects on host tissue in the acute phase. The inflammation and edema were improved in the later phase (10 days). Recovery and healing of the open wounds were observed for all groups at 10 days. The antiseptic irrigation solutions had similar cytotoxic effects on host tissue at 3 days and did not have delayed or compromised wound healing at 10 days when compared to normal saline control. Conclusions: Single short-duration use of these commercially available antiseptic irrigation solutions appears to be safe in an uninfected wound. Data from this study will provide surgeons with useful information regarding the safety of using antiseptic wound irrigation solutions intraoperatively for prevention of surgical site infections.

Repair of a rat calvaria defect with injectable strontium (Sr)-doped polyphosphate dicalcium phosphate dehydrate (P-DCPD) ceramic bone grafts.

The trace element strontium (Sr) enhances new bone formation. However, delivering Sr, like other materials, in a sustained manner from a ceramic bone graft substitute (BGS) is difficult. We developed a novel ceramic BGS, polyphosphate dicalcium phosphate dehydrate (P-DCPD), which delivers embedded drugs in a sustained pattern. This study assessed the in vitro and in vivo performance of Sr-doped P-DCPD. In vitro P-DCPD and 10%Sr-P-DCPD were nontoxic and eluents from 10%Sr-P-DCPD significantly enhanced osteoblastic MC3T3 cell differentiation. A sustained, zero-order Sr release was observed from 10%Sr-P-DCPD for up to 70 days. When using this BGS in a rat calvaria defect model, both P-DCPD and 10% Sr-P-DCPD were found to be biocompatible and biodegradable. Histologic data from decalcified and undecalcified tissue showed that 10%Sr-P-DCPD had more extensive new bone formation compared with P-DCPD 12-weeks after surgery and the 10%Sr-P-DCPD had more organized new bone and much less fibrous tissue at the defect margins. The new bone was formed on the surface of the degraded ceramic debris within the bone defect area. P-DCPD represented a promising drug-eluting BGS for repair of critical bone defects.

Globulin and Albumin/Globulin Ratios as Potential Biomarkers for the Diagnosis of Acute and Chronic Peri-Prosthetic Joint Infections: A Retrospective Study.

Background: Peri-prosthetic joint infection (PJI) is the most serious complication after prosthetic joint replacement. However, the diagnosis of PJI remains challenging for clinicians because of the lack of a gold standard. The purpose of this study was to investigate the diagnostic significance of serum globulin, albumin/globulin, and other biomarkers in acute and chronic periprosthetic infections. Patients and Methods: A retrospective study of 162 patients with PJI and aseptic loosening between January 2016 and March 2021 at our institution was performed in three groups. There were 20 patients with acute infection in group A, 36 patients with chronic infection in group B, and 106 patients with aseptic loosening in group C. Globulin, albumin/globulin, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), platelet count (PLT), mean platelet volume (MPV), d-dimer, and platelet count/mean platelet volume ratio (PMR) levels were recorded. The area under the curve (AUC) was used to measure the diagnostic value of globulin and albumin/globulin with other biomarkers for PJI. Results: Compared with the aseptic loosening group, the acute and chronic PJI group had higher levels of CRP, ESR, d-dimer, globulin, PLT, and PMR (p < 0.01) and lower levels of albumin/globulin and MPV (p < 0.01). The optimal cutoff, AUC, sensitivity, and specificity of CRP, albumin/globulin, ESR, and globulin were: CRP, 8.3 mg/L, 0.903, 78.57%, and 88.68%; albumin/globulin, 1.31, 0.899, 91.07%, and 73.58%; ESR, 32 mm/h, 0.888, 75.%, and 85.85%; globulin, 29.5 g/L, 0.880, 91.07%, and 72.64%. Conclusions: Globulin and albumin/globulin have excellent diagnostic value for acute and chronic PJI and are promising potential biomarkers for the diagnosis of PJI. The diagnostic performance of albumin/globulin is superior to that of ESR and similar to that of CRP.

Electrospun polyvinyl alcohol-collagen-hydroxyapatite nanofibers: a biomimetic extracellular matrix for osteoblastic cells.

The failure of prosthesis after total joint replacement is due to the lack of early implant osseointegration. In this study polyvinyl alcohol-collagen-hydroxyapatite (PVA-Col-HA) electrospun nanofibrous meshes were fabricated as a biomimetic bone-like extracellular matrix for the modification of orthopedic prosthetic surfaces. In order to reinforce the PVA nanofibers, HA nanorods and Type I collagen were incorporated into the nanofibers. We investigated the morphology, biodegradability, mechanical properties and biocompatibility of the prepared nanofibers. Our results showed these inorganic-organic blended nanofibers to be degradable in vitro. The encapsulated nano-HA and collagen interacted with the PVA content, reinforcing the hydrolytic resistance and mechanical properties of nanofibers that provided longer lasting stability. The encapsulated nano-HA and collagen also enhanced the adhesion and proliferation of murine bone cells (MC3T3) in vitro. We propose the PVA-Col-HA nanofibers might be promising modifying materials on implant surfaces for orthopedic applications.

Impacts of age and gender on bone marrow profiles of BMP7, BMPRs and Stro-1⁺ cells in patients with total hip replacement.

PURPOSE: A successful osseointegration relies on the interplay of implant surface and surrounding bone marrow cells. This study was undertaken to investigate the impact of age and gender on the bone marrow composition. METHODS: Bone marrow aspirates were obtained from the discarded metaphysis region of the femoral head in 24 patients with total hip replacement. Flow cytometry was used to measure the expression of Stro-1(+) cells and BMP receptors (BMPRs)-expressing cells. ELISA was used to measure bone marrow aspirate bone morphology protein7 (BMP7) concentration. RESULTS: Our data demonstrates that there are diverse bone marrow profiles (Stro-1(+) cell and BMPRs(+) cells). There are no differences of Stro-1(+) cells, BMPRs(+) cells, and BMP7 concentration between male and female patients. Though there are slight increases in the number of Stro-1(+) cells and BMPRs(+) cells in younger patients (<70 years old) than those of old patients (≥ 70 years old), the difference is not statistically significant. However, we found a close association between the Stro-1(+) cells, BMPR1a cells and BMP7 concentration. In addition, a correlation exists between the number of Stro-1(+) cells and BMIs of these patients. CONCLUSION: Our data suggests that the age and gender of THR patients have little impact on their bone marrow osteogenic potential. The significance of the number of the Stro-1(+) with BMPRs expression on the implant fixation and osseointegration warrants further investigation.

Attachment and Growth of Fibroblasts and Tenocytes Within a Porous Titanium Scaffold: A Bioreactor Approach.

Background: Direct attachment of tendons to metallic implants is important in orthopedics. Tissue integration depends on scaffold microstructure and composition. This study evaluated the effect of pore size of titanium on the viability and function of fibroblasts and tenocytes in a dynamic bioreactor. Methods: Standardized Ti porous cylinders with 3 pore sizes (400, 700, and 1000 µm) were seeded with fibroblasts or tenocytes (4500 cells/µL) in silicon tubes. Cells were analyzed via alamarBlue (AB) assay in addition to scanning electron microscopy at day 7 (fibroblasts) or day 8 (tenocytes) and day 15. AB functions as a cell health indicator where functional living cells reduce the resazurin dye (blue) in the solution to resorufin (pink), and cell viability can be quantified via spectroscopy. Results: At day 7, fibroblasts cultured on all sizes reduced AB, with significant differences noted between 400 vs 1000 µm (P = .013) and 700 vs 1000 µm (P = .001). At day 15, fibroblasts reduced AB on all sizes with a significant difference noted between 700 vs 1000 µm (P = .004). Fibroblasts on all 3 pore sizes increased AB reduction from day 7 to day 15. Tenocytes reduced AB with significant differences between the 400 vs 700 µm (P = .049) and the 400 vs 1000 µm pore sizes at day 8. In contrast, tenocyte reduction of AB decreased from day 8 to day 15. Scanning electron microscopy performed on fibroblast cylinders showed fibroblasts reached the surface of the cylinders, confirming interconnectivity. Conclusions: While both fibroblasts and tenocytes penetrated the pores, fibroblasts preferred larger size, whereas tenocytes favored smaller size. Results are encouraging since soft-tissue attachment to a metallic scaffold is difficult but clinically desirable. Future studies could be performed in an in vivo animal model.

Osteoblastic differentiation and bactericidal activity are enhanced by erythromycin released from PCL/PLGA-PVA coaxial nanofibers.

Prosthesis with antibiotic-eluting nanofibrous (NF) coating represents coating alternative to prevent periprosthetic joint infection (PJI). In this study, four formulas of erythromycin (EM)-embedded both in core and sheath components of coaxial PCL/PLGA-PVA NF coatings were developed: EM 0 (no EM), EM 100 (100 µg/mL), EM500 (500 µg/mL) and EM1000 (1000 µg/mL). EM doping altered the physicochemical and structural properties of NFs to some extent, including the increase of NF porosity and surface wettability. A sustained EM release from EM-NFs for >4 weeks was observed. Eluents collected from EM-NFs showed strong zone of inhibition (ZOI) to Staphylococcus aureus growth and the sizes of ZOI positively related to the amount of EM released. EM-NFs were nontoxic to rat bone marrow stem cells (rBMSCs). Cell growth was significantly enhanced when comparing rBMSCs cultured on EM-NFs (EM0 and EM 100) to those cultured on NF-free control. Cell differentiation (ALP activity) was notably enhanced by EM100, compared to control and EM0. Eluents from EM-NFs on rBMSCs were also investigated. The presence of 10% EM-NF eluents inhibited the growth of rBMSCs, which was proportional to the amount of EM doped. The ALP activity was notably enhanced by eluents from EM-NFs with the highest activity in EM100 compared to control and EM0. Our data indicate that EM-doped PCL/PLGA-PVA coaxial NF coatings have a great potential to be applied as a new implant coating matrices. Further in vivo testing in animal models is currently planned that should represent the first step in predicting the clinical outcomes of EM-eluting NF coating approach.

Common Wound Irrigation Solutions Produce Different Responses in Infected vs Sterile Host Tissue: Murine Air Pouch Infection Model.

Background: Despite desirable microbicidal actions of irrigation solutions in surgical site infection treatment, several studies demonstrate potential cytotoxic effects. This study investigated tissue damage caused by irrigation solutions in the presence or absence of infection. Methods: Air pouches were created in 60 mice and evenly divided into 2 groups as infected with Staphylococcus aureus and control. Groups were then subdivided both by type of solution and by timing after irrigation. Solutions included control (0.9% saline), bacitracin (33 IU/ml), 0.2% sodium oxychlorosene, 0.05% chlorhexidine gluconate, and 0.013% benzalkonium chloride. Results: Inflammation decreased in infected pouches compared to the sterile ones for all solutions except bacitracin on day 0 and for all on day 7. On day 0, infected pouches had increased necrosis with bacitracin (P = .006), chlorhexidine gluconate (P = .18), and benzalkonium chloride (P = .07); on day 7, there was decreased necrosis in infected pouches for all solutions (P < .05) except for sodium oxychlorosene (P = .18). Edema decreased in infected pouches on day 0 for all solutions. On day 7, infected pouches had decreased edema with 0.9% saline, bacitracin, and benzalkonium chloride (P < .05) and increased edema with chlorhexidine gluconate (P < .05) and sodium oxychlorosene (P = .069). Bacitracin allowed for more bacteria growth than sodium oxychlorosene (P = .024), chlorhexidine gluconate (P = .025), and benzalkonium chloride (P = .025). Conclusions: The presence of bacteria led to less immediate tissue inflammation and edema, while tissue necrosis varied over time. The current study may guide surgeons on which solution to use and whether to irrigate a possibly sterile wound or joint.

Hepatitis C virus infection increases the risk of adverse outcomes following joint arthroplasty: A meta-analysis of observational studies.

BACKGROUND: Whether hepatitis C virus (HCV)-positive patients are at risk for increased complications and long hospital stay following total joint arthroplasty (TJA) remains unclear. Therefore we performed a meta-analysis aiming to answer the following question: (1) are there differences in postoperative complications including joint infection and mortality between patients with or without hepatitis C following TJAs? (2) Are patients without HCV be associated with less blood loss, shorter hospital stay, lower readmission rate, higher function scores, lower revision and reoperation rates than patients with HCV? METHODS: A meta-analysis was conducted to pool data and quantitatively assessing the association between HCV infection and risks for adverse postoperative outcomes. A systematic search of all published studies concerning HCV and TJA was performed in five bibliographic databases, including PubMed, EMBASE, China National Knowledge Infrastructure, Web of Science, and the Cochrane Library databases. Random-effects meta-analysis of odds ratios (OR) was accomplished according to the classification of adverse events, subgroup analyses were performed based on surgery type. RESULTS: Fifteen eligible observational studies were included with a sample size of 9,788,166 patients. Overall pooled data revealed the increased risk of overall complications, including medical and surgical complications, in HCV-positive patients undergoing TJA compared with than in HCV-negative people (OR 1.57; 95%CI: 1.44-1.71 [p<0.00001]). Joint infections were highly common in HCV-positive patients undergoing lower-extremity TJA (OR 2.06; 95%CI: 1.73-2.47 [p<0.00001]). Furthermore, HCV infections were associated with high rates of reoperations and revisions (OR 1.47; 95%CI: 1.40-1.55 [p<0.00001]). CONCLUSIONS: Patients with hepatitis C have an increased risk of adverse outcomes post-TJA and a high risk of reoperation and revision that is partially attributed to postoperative complications, particularly joint infections. LEVEL OF EVIDENCE: III; systematic review and meta-analysis.

Impacts of compacting methods on the delivery of erythromycin and vancomycin from calcium polyphosphate hydrogel matrices.

Designing hydrogels for controlled drug delivery remains a big challenge. We developed a calcium polyphosphate hydrogel (CPP) as matrix for delivery of vancomycin (VCM) and erythromycin (EM) by unique ionic binding and physical wrapping. In this continuing study, we investigated if gel discs prepared by mechanical compaction (at 3000 psi pressure, C-discs) is superior to that of discs prepared by regular manual compaction (M-discs) for the release of VCM and EM (10 wt.%). Data demonstrated a significant reduction of burst release of VCM and EM in C-discs (1.8% and 5%, respectively) as compared to that from M-discs within 72 hr (55% and 60%, respectively, p < 0.05). In addition, C-discs significantly extended the VCM release (1500 hr) and EM (800 hr) as compared to M-discs (160 and 96 hr, respectively, p < 0.05). The VCM released from C-discs retained its bactericidal activity much longer (1500 hr) than that from M-discs (700 hr, p < 0.05). Raman Spectroscopy indicated an ionic bond of both VCM and EM with fully hydrated polyphosphate chains of CPP hydrogel matrix for both M-discs and C-discs. Micro CT showed that C-discs had much denser microstructures and less number/depth of microcracks as a result of high pressure. We propose that CPP hydrogel represents an excellent tool for the controllable and sustained delivery of VCM and EM. Extensive experiments are currently underway to evaluate the potential impacts of the modification of compaction techniques, other antibiotics, gel concentrations on the drug release, degradation behavior and infection control both in vitro and in vivo.