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.

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.

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.

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.

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.

A Pan-Cancer Analysis of the Oncogenic Role of BCL7B: A Potential Biomarker for Prognosis and Immunotherapy.

Background: Previous studies have partly explored the role of B-cell CLL/lymphoma 7 protein family member B (BCL7B) in tumorigenesis and development. However, the prognosis and immunoregulatory value of BCL7B in pan-cancer patients remains unclear. Methods: Through The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases, the distinct expression of BCL7B gene in 33 tumors and adjacent normal tissues was analyzed. The Kaplan-Meier method (univariate Cox regression analysis and Kaplan-Meier curve) was used to identify the cancer types whose BCL7B gene expression was related to prognosis. The receiver operating characteristic (ROC) curve was used to elucidate the diagnosis value of BCL7B gene. Spearman's rank correlation coefficient was used to explore the relationship between BCL7B gene expression and immune cell infiltration, immune checkpoints, DNA methylation, DNA repair genes, immune-activating genes, immune-suppressing genes, immune subtypes, tumor mutation burden (TMB), and microsatellite instability (MSI). The Wilcoxon rank sum test and Kruskal-Wallis test were used to compare the expression of BCL7B gene in tumor tissues with different clinicopathological features. Gene set enrichment analysis (GSEA) was conducted to identify the tumor-related pathways in pan-cancer. The Human Protein Atlas (HPA) database was used to verify the BCL7B gene expression at the protein level. Results: High expression of BCL7B was associated with an inferior prognosis in glioblastoma multiforme (GBM), glioma (GBMLGG), kidney chromophobe (KICH), brain lower grade glioma (LGG), oral squamous cell carcinoma (OSCC), rectum adenocarcinoma (READ), and uveal melanoma (UVM). Low expression of BCL7B was associated with a poor prognosis in kidney renal clear cell carcinoma (KIRC), kidney renal papillary cell carcinoma (KIRP), skin cutaneous melanoma (SKCM), thyroid carcinoma (THCA), and sarcoma (SARC). The BCL7B gene expression had varying degrees of correlation with 24 immune cell subsets in 37 tumor environments such as adrenocortical carcinoma (ACC) and bladder urothelial carcinoma (BCLA). Spearman's rank correlation coefficient showed that BCL7B gene expression had different degrees of correlation with 47 immune checkpoints, 46 immune-activating genes, 24 immune-suppressing genes, 5 DNA repair genes, and DNA methylation, TMB, and MSI in 39 tumors. GSEA suggested that BCL7B was notably associated with cancer-related and immune-related pathways. Conclusion: In summary, BCL7B gene has a high diagnostic and prognostic value in pan-cancer and is related to the infiltration of 24 immune cell subsets in pan-cancer.

Immunomodulatory mechanisms of abatacept: A therapeutic strategy for COVID-19.

Coronavirus disease 2019 (COVID-19) caused by coronavirus-2 (SARS-CoV-2) infection has rapidly spread throughout the world and become a major threat to human beings. Cytokine storm is a major cause of death in severe patients. Abatacept can suppress cytokines used as antirheumatic drugs in clinical applications. This study analyzed the molecular mechanisms of abatacept treatment for COVID-19. Differentially expressed genes (DEGs) were identified by analyzing expression profiling of abatacept treatment for rheumatoid arthritis (RA) patients and SARS-CoV-2 infection patients. We found that 59 DEGs were upregulated in COVID-19 patients and downregulated following abatacept treatment. Gene set enrichment analysis (GSEA) and Gene Ontology (GO) analysis showed that immune and inflammatory responses were potential regulatory mechanisms. Moreover, we verified 8 targeting genes and identified 15 potential drug candidates for the treatment of COVID-19. Our study illustrated that abatacept could be a promising property for preventing severe COVID-19, and we predicted alternative potential drugs for the treatment of SARS-CoV-2 infection.

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.

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.

Irrigation Solutions Negatively Affect the Viability and Function of Human Fibroblasts: An in vitro Study.

Introduction: Multiple irrigation solutions are used in orthopedic surgeries although there are limited studies on their lasting effects on human tissues. The purpose of this work was to investigate the cytotoxic effects of the irrigation solutions Bacitracin, Clorpactin (sodium oxychlorosene), Irrisept (0.05% chlorhexidine gluconate), and Bactisure (ethanol 1%, acetic acid 0.6%, sodium acetate 0.2%, benzalkonium chloride 0.013%, and water) on 3D cultures of human fibroblasts. Methods: Two independent experiments with 6 replicates were performed for the following conditions: Control (saline), bacitracin, Clorpactin, Irrisept, and Bactisure. Human fibroblast cell sheets were exposed to these solutions (1 or 2 min), followed by three washes with warm saline. Cell sheets were then cultured for additional 5- and 7-day posttreatment. Cell viability was measured using the alamarBlue (AB) assay. The more cytotoxic the irrigant, the lower the AB reduction. Results: For 1-min exposure time, significant differences in AB reduction were noted in Clorpactin, Irrisept, and Bactisure groups compared to control at both 5 days (Clorpactin p = 0.0003, Irrisept p = 7.31 × 10-15, Bactisure p = 6.86 × 10-14) and 7 days posttreatment (all groups p < 0.0001). The results were similar in the 2-min exposure groups. Bacitracin-treated fibroblasts displayed no significant difference at all measurement times compared to control. Discussion: Impacts of irrigation solution exposure on cell viability were varied. Irrisept and Bactisure showed the highest cell toxicity even after a brief exposure (1 min), while bacitracin and Clor-pactin exposure showed smaller impacts on cell viability as compared to saline controls. This in vitro study provided insight into the effects of the irrigants on human cells and provides the groundwork essential to move to in vivo studies. Our findings raised the concern that some irrigation solutions may have negative impacts on wound healing and healthy cellular response.

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.

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.

Comparing the physicochemical properties of dicalcium phosphate dihydrate (DCPD) and polymeric DCPD (P-DCPD) cement particles.

We developed a new and injectable poly-dicalcium phosphate dihydrate (P-DCPD) forming cement. The key structural difference between P-DCPD and classical DCPD is that P-DCPD is composed of interconnected P-DCPD crystals by interlocking to the polyphosphate chains. In contrast, DCPD is composed of a package of DCPD crystals with weak mutual ionic bonding. The purpose of this continuing study was to compare the physicochemical properties between P-DCPD and DCPD cement particles. Data collected from SEM, X-ray diffraction, and Raman Spectroscopy approaches demonstrated that P-DCPD has a more stable chemical structure than DCPD as evidenced by much less transformation to hydroxyapatite (HA) during setting. Nanoindentation showed a similar hardness while the elastic modulus of P-DCPD is much lower than DCPD that might be due to the much less HA transformation of P-DCPD. P-DCPD has much lower zeta potential and less hydrophilicity than DCPD because of its entangled and interconnected polyphosphate chains. It is expected that superhydrophilic DCPD undergoes faster dissolution than P-DCPD in an aqueous environment. Another interesting finding is that the pH of eluent from P-DCPD is more neutral (6.6-7.1) than DCPD (5.5-6.5). More extensive experiments are currently underway to further evaluate the potential impacts of the different physiochemical performance observed of P-DCPD and DCPD cement particles on the biocompatibility, degradation behavior and bone defect healing efficacy both in vivo and in vitro.

Properties of erythromycin-loaded polymeric dicalcium phosphate dehydrate bone graft substitute.

A self-setting, injectable polymeric dicalcium phosphate dehydrate bone graft substitute that is mechanically strong and has excellent cohesion was developed. We assessed the performance of erythromycin-loaded polymeric dicalcium phosphate dehydrate cement. Its properties include drug release, growth inhibition against Staphylococcus aureus and biocompatibility with osteoblastic MC3T3 cells. The impact of erythromycin loading on cement injectability, setting time, and mechanical strength were also evaluated. A sustained, low burst release of erythromycin was observed. Eluents collected from erythromycin-loaded cement showed a considerable zone of inhibition for up to 28 days. Direct contact of erythromycin-loaded cement discs with agar plate showed a similarly sizable zone of inhibition for up to 22 days. Degraded ceramic residues had strong zones of inhibition as well. While the erythromycin-loaded cement was injectable, a notable delay of the setting time was observed (49.2 ± 6.8 min) as compared with control (drug-free cement, 12.2 ± 2.6 min). A slight increase in compressive strength (60.83 ± 6.28 MPa) was observed in erythromycin-loaded cement as compared with control (59.41 ± 6.48 MPa). Erythromycin-loaded cement was biocompatible although reduced cell growth was observed in the presence of the cement eluent. We propose that the bactericidal efficacy of erythromycin-loaded cement was caused by the combined effects of erythromycin released and exposed on the contact surface of degrading ceramics. Our data may elucidate the future application of polymeric dicalcium phosphate dehydrate bone graft substitute for the treatment of orthopedic infections and opportunities to use other antibiotics and applications considering its comparable handling and mechanical strength to poly (methyl methacrylate) cements.

Biomechanical strength comparison of pedicle screw augmentation using poly-dicalcium phosphate dihydrate (P-DCPD) and polymethylmethacrylate (PMMA) cements.

STUDY DESIGN: A basic science, hypothesis-driven experimental study of the biomechanics of two bone cements in their ability to augment pedicle screws in bone foam. OBJECTIVE: The purpose of our study was to compare the pullout and torque resistance of conventional pedicle screws (CPS) augmented with either polymethylmethacrylate (PMMA) or poly-dicalcium phosphate dihydrate (P-DCPD) cement in polyurethane foam blocks mimicking osteoporotic bone. P-DCPD cement has attractive safety characteristics such as non-exothermic curing and drug-eluting capacity. PMMA cement lacks these safety features yet is the current standard in pedicle screw augmentation. METHODS: Standardized low-density polyurethane open-cell foam blocks were instrumented with conventional pedicle screws and categorized into three groups of six each. Group 1 was the control group and no cement was used. Groups 2 and 3 were augmented with PMMA and P-DCPD, respectively. An Instron machine applied an axial load to failure at a rate of 2 mm/min for 3 min and a torsional load to failure at a rate of 1°/s. Failure was defined by an evident drop in the load after maximum value. RESULTS: Maximal pullout load for PMMA and P-DCPD was significantly greater than control (p < 0.0001). Interestingly, there was no significant difference in the pullout load to failure for the PMMA and P-DCPD groups. Analysis showed significant difference in torsional resistance between PMMA and P-DCPD, with PMMA having greater resistance (p = 0.00436). CONCLUSIONS: No difference was observed between PMMA and P-DCPD in pullout load to failure conducted in low-density open-cell, rigid foam blocks. Although a significant difference did exist in our torque analysis, the clinical significance of such a load on a native spine is questionable. Further investigation is warranted for this promising compound that seems to be comparable in pullout resistance to PMMA and offers attractive safety features. LEVEL OF EVIDENCE: Basic science, not applicable.

Comparing the release of erythromycin and vancomycin from calcium polyphosphate hydrogel using different drug loading methods.

Calcium polyphosphate (CPP) hydrogel is used to load erythromycin (EM) and vancomycin (VCM) by means of two loading methods: they are either added directly to the formed CPP hydrogel (Gel Mixture method) or mixed with CPP powders, followed by the formation of CPP-antibiotic hydrogel (Powder Mixture method). The release of loaded antibiotics from CPP hydrogel is measured up to 48 hr. Compared to Powder Mixture method, Gel Mixture method significantly reduced the burst release of embedded antibiotics. A significant change in CPP hydrogel Raman characteristic peaks is observed only in Gel Mixture method, indicating a close interaction between embedded antibiotics with CPP hydrogel matrix. In contrast, a similarity between characteristic peaks of CPP hydrogel and Powder Mixture method shows that antibiotic incorporation does not interfere with CPP gel formation, resulting in no ionic interaction between antibiotic and polyphosphate chains. Rheometer analysis further confirms that the hydrophobic nature of EM impacts the viscoelastic properties of CPP hydrogel, whereas the hydrophilic VCM exhibits a higher loading efficiency. The potential application of CPP hydrogel as a ceramic matrix for sustained drug release warrants further investigation.

FiberWire vs FiberTape: Comparison of Bacterial Adherence in a Murine Air Pouch Wound Model.

BACKGROUND: For high-tensile strength sutures, past research has largely focused on mechanical properties or bacterial adherence across various manufacturers. PURPOSE: This study investigated high-tensile strength sutures with different shapes but otherwise identical composition. The purpose was to evaluate the differences between high-tensile strength suture wire and suture tape relative to bacterial adherence and bacterial retention after washout. STUDY DESIGN: Controlled laboratory study. METHODS: Sutures were implanted in dorsal air pouches of 72 BALB/cJ mice. Experimental pouches were inoculated with Staphylococcus aureus; no bacteria were used in the control conditions. The mice were randomized into 3 groups: group 1 underwent suture extraction 7 days after implantation; group 2 underwent an irrigation procedure, followed by immediate suture extraction on day 7; and group 3 underwent an irrigation procedure on day 7, with delayed suture extraction on day 14 after implantation. The sutures were evaluated using confocal microscopy; electron microscopy; and spectrophotometry, through which optical density, as measured by the amount of scattered light, is directly correlated with the number of bacteria. Histological assessment was performed on the pouches. RESULTS: Optical density (mean ± SD) was significantly higher for FiberTape sutures than for FiberWire sutures, respectively, at the 2-hour time point for all groups (group 1, 0.0550 ± 0.0081 vs 0.0162 ± 0.006 [P = .0054]; group 2, 0.0225 ± 0.0049 vs 0.0056 ± 0.0006 [P = .0045]; group 3, 0.055 ± 0.0222 vs 0.0043 ± 0.0005 [P = .0103]). Additionally, groups 2 and 3 showed statistically significant results at the 4-hour time points (group 2, 0.0384 ± 0.0087 vs 0.0145 ± 0.0042 [P = .0280]; group 3, 0.0532 ± 0.0159 vs 0.0101 ± 0.0025 [P = .0058]). The wash fluid also demonstrated significantly greater optical density for the FiberTape than the FiberWire sutures, respectively, at the 2-hour time point for all groups (group 1, 0.1657 ± 0.0319 vs 0.0317 ± 0.008 [P = .0063]; group 2, 0.0522 ± 0.0156 vs 0.0127 ± 0.0022 [P = .0219]; group 3, 0.1707 ± 0.0205 vs 0.0191 ± 0.0053 [P < .0001]). No bacterial growth occurred in the control conditions. Histological assessment revealed only mild inflammation in the control groups as compared with more severe responses in the experimental groups at all time points. CONCLUSION: FiberTape was associated with increased bacterial adhesion as well as retention as compared with FiberWire in an in vivo murine wound model. CLINICAL RELEVANCE: This study demonstrates that suture design influences the occurrence of and ability to clear surgical infection and must be considered when selecting high-tensile strength sutures in a clinical setting.

Preparation of electrospun nanofibers with desired microstructures using a programmed three-dimensional (3D) nanofiber collector.

The traditional electrospinning process produces dense two-dimensional (2D) nanofiber (NF) sheets that limit cell infiltration and proliferation. Our previous study demonstrated that 3D NF sheets could be formed on an NF collector surface mounted with multiple movable needles through the corona discharge. In this study, we developed a programmed electrospun 3D NF collector. It can precisely control the moving speed of NF collector during electrospinning; thereby fabricating 3D NFs with desired microstructures (pore size, pore volume, and interconnectivity). Four types of polycaprolactone (PCL) 3D NF matrices with different microstructures can be obtained concurrently on the NF collector surface, which are set by different forward moving speed of the NF collector device: NF-zero (no move, as control), NF-low (0.085 mm/min), NF-mid (0.158 mm/min) and NF-high (0.232 mm/min). A linear increase of the NF sheet thickness (from 0.21 mm to 0.91 mm) was recorded with accelerating collector movement. Quantitative analysis using scanning electron microscopy (SEM), micro-computed tomography (µ-CT), and confocal laser scanning microscopy (CLSM) showed a monotonic increase of pore size and porosity with the increase of collector moving speeds. The collector movement also impacted the crystallinity and mechanical properties of the NFs. When prepared at high collector speed, the NFs showed improved proliferation and differentiation (p < .05) of pre-osteoblastic MC3T3 cells compared to the NFs from the static collector. A programmed NF collector device allows for the reproducible, precise and continuous fabrication of 3D NFs with tailorable geometry and microstructures. This simple, controllable, one-step process could promote the clinical translation of electrospun NFs in tissue engineering and regenerative medicine.

Blood metal levels, leucocyte profiles, and cytokine profiles in patients with a modular dual-mobility hip prosthesis: early results from a prospective cohort study.

AIMS: The aim of this study was to evaluate blood metal ion levels, leucocyte profiles, and serum cytokines in patients with a total hip arthroplasty (THA) involving modular dual-mobility components. PATIENTS AND METHODS: A total of 39 patients were recruited, with clinical follow-up of up to two years. Outcome was assessed using the Harris Hip Score (HHS, the 12-Item Short-Form Health Survey (SF-12), the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and a visual analogue scale (VAS) for pain. Blood concentrations of cobalt (Co), chromium (Cr), and serum cytokines were measured. Subpopulations of leucocytes were analyzed by flow cytometry. RESULTS: The clinical performance was good. Blood Co levels (ref 1.0 µg/l) were mildly elevated in seven patients at three months, and two patients at two years' follow-up. The preoperative Cr levels were normal except for one patient with a detectable Cr (1.2 µg/l). Cr levels were detectable in three patients at three months, two patients at one year, and three patients at two years' follow-up. No patients had symptoms suggestive of failure. Although flow cytometry showed constant circulating leucocyte profiles, there was a significant reduction of serum interleukin (IL)-4, IL-5, and interferon gamma (IFNγ) postoperatively compared with the preoperative levels (p < 0.05). CONCLUSION: These results suggest that THA using modular dual-mobility components is safe. This allows an opportunity to use a large femoral head and a thick polyethylene bearing surface, which is especially useful in revision procedures or high-risk situations when added stability is required. Cite this article: Bone Joint J 2019;101-B:1035-1041.