UNASSIGNED: Implants are widely used in the field of orthopedics and dental sciences. Titanium (TI) and its alloys have become the most widely used implant materials, but implant-associated infection remains a common and serious complication after implant surgery. In addition, titanium exhibits biological inertness, which prevents implants and bone tissue from binding strongly and may cause implants to loosen and fall out. Therefore, preventing implant infection and improving their bone induction ability are important goals.
UNASSIGNED: To study the antibacterial activity and bone induction ability of titanium-copper alloy implants coated with nanosilver/poly (lactic-co-glycolic acid) (NSPTICU) and provide a new approach for inhibiting implant-associated infection and promoting bone integration.
UNASSIGNED: We first examined the in vitro osteogenic ability of NSPTICU implants by studying the proliferation and differentiation of MC3T3-E1 cells. Furthermore, the ability of NSPTICU implants to induce osteogenic activity in SD rats was studied by micro-computed tomography (micro-CT), hematoxylin-eosin (HE) staining, masson staining, immunohistochemistry and van gieson (VG) staining. The antibacterial activity of NSPTICU in vitro was studied with gram-positive Staphylococcus aureus (Sa) and gram-negative Escherichia coli (E. coli) bacteria. Sa was used as the test bacterium, and the antibacterial ability of NSPTICU implanted in rats was studied by gross view specimen collection, bacterial colony counting, HE staining and Giemsa staining.
UNASSIGNED: Alizarin red staining, alkaline phosphatase (ALP) staining, quantitative real-time polymerase chain reaction (qRT-PCR) and western blot analysis showed that NSPTICU promoted the osteogenic differentiation of MC3T3-E1 cells. The in vitro antimicrobial results showed that the NSPTICU implants exhibited better antibacterial properties. Animal experiments showed that NSPTICU can inhibit inflammation and promote the repair of bone defects.
UNASSIGNED: NSPTICU has excellent antibacterial and bone induction ability, and has broad application prospects in the treatment of bone defects related to orthopedics and dental sciences.

The biofilm-mediated implant infections pose a huge threat to human health. It is urgent to explore strategies to reverse this situation. Herein, we design 3-amino-1,2,4-triazole-5-thiol (ATT)-modified gold nanoclusters (AGNCs) to realize biofilm-targeting and near-infrared (NIR)-II light-responsive antibiofilm therapy. The AGNCs can interact with the bacterial extracellular DNA through the formation of hydrogen bonds between the amine groups on the ATT and the hydroxyl groups on the DNA. The AGNCs show photothermal properties even at a low power density (0.5 W/cm2) for a short-time (5 min) irradiation, making them highly effective in eradicating the biofilm with a dispersion rate up to 90 %. In vivo infected catheter implantation model demonstrates an exceptional high ability of the AGNCs to eradicate approximately 90 % of the bacteria encased within the biofilms. Moreover, the AGNCs show no detectable toxicity or systemic effects in mice. Our study suggests the great potential of the AGNCs for long-term prevention and elimination of the biofilm-mediated infections.

Owing to the presence of microbial biofilm on the implant, the eradication of biofilm-associated infections poses a challenge for antibiotic therapies. The study aimed to investigate the efficacy and safety of the novel antibiotic agent TNP-2092 in the context of implant infections. In vivo, rats with periprosthetic joint infection (PJI) treated with antibiotics showed an increase in body weight and decrease in swelling, temperature, and width of knee, compared with the control group. Meanwhile, inflammatory markers in synovium and serum were decreased in the TNP-2092 group, consistent with the pathological results. Moreover, TNP-2092 was effective in eliminating bacteria and disruption biofilm formation, and further alleviated the abnormal bone absorption and reactive bone changes around the prosthesis. In conclusion, intra-articular injection of TNP-2092 is safe and effective in treating knee PJI in a rat model. The study provides a foundation for the future utilization of TNP-2092 in the management of implant-related infections.

The threat of infection during implant placement surgery remains a considerable burden for millions of patients worldwide. To combat this threat, clinicians employ a range of anti-infective strategies and practices. One of the most common interventions is the use of prophylactic antibiotic treatment during implant placement surgery. However, these practices can be detrimental by promoting the resilience of biofilm-forming bacteria and enabling them to persist throughout treatment and re-emerge later, causing a life-threatening infection. Thus, it is of the utmost importance to elucidate the events occurring during the initial stages of bacterial surface attachment and determine whether any biological processes may be targeted to improve surgical outcomes. Using gene expression analysis, we identified a cellular mechanism of S. aureus which modifies its cell surface charge following attachment to a medical grade titanium surface. We determined the upregulation of two systems involved in the d-alanylation of teichoic acids and the lysylation of phosphatidylglycerol. We supported these molecular findings by utilizing synchrotron-sourced attenuated total reflection Fourier-transform infrared microspectroscopy to analyze the biomolecular properties of the S. aureus cell surface following attachment. As a direct consequence, S. aureus quickly becomes substantially more tolerant to the positively charged vancomycin, but not the negatively charged cefazolin. The present study can assist clinicians in rationally selecting the most potent antibiotic in prophylaxis treatments. Furthermore, it highlights a cellular process that could potentially be targeted by novel technologies and strategies to improve the outcome of antibiotic prophylaxis during implant placement surgery. STATEMENT OF SIGNIFICANCE: The antibiotic tolerance of bacteria in biofilm is a well-established phenomenon. However, the physiological adaptations employed by Staphylococcus aureus to increase its antibiotic tolerance during the early stages of surface attachment are poorly understood. Using multiple techniques, including gene expression analysis and synchrotron-sourced Fourier-transform infrared microspectroscopy, we generated insights into the physiological response of S. aureus following attachment to a medical grade titanium surface. We showed that this phenotypic transition enables S. aureus to better tolerate the positively charged vancomycin, but not the negatively charged cefazolin. These findings shed light on the antibiotic tolerance mechanisms employed by S. aureus to survive prophylactically administered antibiotics and can help clinicians to protect patients from infections.

Periprosthetic joint infection (PJI) is a challenging complication that can occur following joint replacement surgery. Efficacious strategies to prevent and treat PJI and its recurrence remain elusive. Commensal bacteria within the gut convey beneficial effects through a defense strategy named \"colonization resistance\" thereby preventing pathogenic infection along the intestinal surface. This blueprint may be applicable to PJI. The aim is to investigate Lactobacillus acidophilus spp. and their isolated extracellular-derived proteins (LaEPs) on PJI-relevant Staphylococcus aureus, methicillin-resistant S. aureus, and Escherichia coli planktonic growth and biofilm formation in vitro. The effect of LaEPs on cultured macrophages and osteogenic, and adipogenic human bone marrow-derived mesenchymal stem cell differentiation is analyzed. Data show electrostatically-induced probiotic-pathogen species co-aggregation and pathogenic growth inhibition together with LaEP-induced biofilm prevention. LaEPs prime macrophages for enhanced microbial phagocytosis via cathepsin K, reduce lipopolysaccharide-induced DNA damage and receptor activator nuclear factor-kappa B ligand expression, and promote a reparative M2 macrophage morphology under chronic inflammatory conditions. LaEPs also significantly augment bone deposition while abating adipogenesis thus holding promise as a potential multimodal therapeutic strategy. Proteomic analyses highlight high abundance of lysyl endopeptidase, and urocanate reductase. Further, in vivo analyses are warranted to elucidate their role in the prevention and treatment of PJIs.

Host immune systems serving as crucial defense lines are vital resisting mechanisms against biofilm-associated implant infections. Nevertheless, biofilms hinder the penetration of anti-bacterial species, inhibit phagocytosis of immune cells, and frustrate host inflammatory responses, ultimately resulting in the weakness of the host immune system for biofilm elimination. Herein, a cell-like construct is developed through encapsulation of erythrocyte membrane fragments on the surface of Fe3 O4 nanoparticle-fabricated microbubbles and then loaded with hydroxyurea (EMB-Hu). Under ultrasound (US) stimulation, EMB-Hu undergoes a stable oscillation manner to act in an \"exocytosis\" mechanism for disrupting biofilm, releasing agents, and enhancing penetration of catalytically generated anti-bacterial species within biofilms. Additionally, the US-stimulated \"exocytosis\" by EMB-Hu can activate pro-inflammatory macrophage polarization and enhance macrophage phagocytosis for clearance of disrupted biofilms. Collectively, this work has exhibited cell-like microbubbles with US-stimulated \"exocytosis\" mechanisms to overcome the biofilm barrier and signal macrophages for inflammatory activation, finally achieving favorable therapeutic effects against implant infections caused by methicillin-resistant Staphylococcus aureus (MRSA) biofilms.

Preventing bacterial infection and promoting osseointegration are essential for the long-term success of titanium (Ti) implants. In this study, we developed a multifunctional nanocoating on Ti mini-implants to simultaneously address these challenges. The nanocoating consists of self-assembled antimicrobial peptides GL13K and silver nanoparticles, referred to as Ag-GL. Our results showed that the Ag-GL coating did not alter the surface morphology of the mini-implants. Ag-GL coated mini-implants demonstrated a two orders of magnitude reduction in colony-forming unit (CFU) values compared to the noncoated eTi group, resulting in minimal inflammation and no apparent bone destruction in a bacterial infection in vivo model. When evaluating osseointegration properties, micro-CT analysis, histomorphometric analysis, and pull-out tests revealed that the Ag-GL coating significantly enhanced osseointegration and promoted new bone formation in vivo.

Background In this study, we aimed to determine if there is a difference in the rates of wound dehiscence, delayed union, nonunion, and unanticipated surgery after the use of bioabsorbable local antibiotic-delivery systems (LADS), specifically comparing antibiotic-impregnated calcium sulfate pellets (Osteoset-T, Wright Medical Technology Inc., Arlington, TN, USA, hereafter referred to as beads) and chitosan sponge (Sentrex BioSponge, Bionova Medical, Germantown, TN, USA, hereafter referred to as sponges) in the management of acute and chronic extremity wounds. Methodology We conducted a retrospective comparative cohort study in the setting of a level 1 trauma center. All patients who received either beads or sponges as an adjunct to surgical debridement from January 2010 to December 2017 were included, and 136 patients met the inclusion criteria. The intervention studied was extremity wounds that were treated with bioabsorbable LADS, either beads or sponges. The main outcome measurement was wound dehiscence and the need for unanticipated surgery. Results Of the 136 patients in the study cohort, 78% (106/136) were treated with beads, and 22% (30/136) were treated with sponges. Of the 136 patients, 50 (37%) experienced wound dehiscence, and 49 patients required unanticipated surgery. Overall, 62% (31/50) of patients with wound dehiscence and 67.4% (33/49) of patients requiring unanticipated surgery were seen in the bead cohort (p = 0.0001 and 0.025, respectively). However, in multivariable analyses, we found that the odds of having wound dehiscence and undergoing unanticipated surgery were, respectively, 4.9 (p = 0.001) and 2.8 (p = 0.021) times more likely to occur in the sponge than in the bead group. Conclusions Sentrex sponges appear to be associated with higher rates of wound dehiscence and the need for unanticipated surgery compared to Osteoset beads.

Implant infections are difficult to cure by traditional antibiotic therapy due to bacterial biofilm-induced antibiotic tolerance and impaired immune responses. To efficiently treat implant infections, therapeutic agents need to kill bacteria and regulate the inflammatory response of immune cells during the biofilm elimination process. Herein, multifunctional smart hollow Cu2MoS4 nanospheres (H-CMS NSs) with pH-responsive enzyme-like activities were prepared for self-adaptively eliminating biofilms and regulating the inflammation of macrophages in implant infections. During biofilm infection, the tissue microenvironment around implants is acidic. H-CMS NSs with oxidase (OXD)/peroxidase (POD)-like activities can catalyze reactive oxidative species (ROS) generation for directly killing bacteria and polarizing macrophages to a proinflammatory phenotype. Moreover, the POD-like activity and antibacterial property of H-CMS NSs can be further enhanced under ultrasound (US) irradiation. After the elimination of biofilms, the tissue microenvironment around implants shifts from acidic to neutral. H-CMS NSs show catalase (CAT)-like activity and eliminate excessive ROS, which polarizes macrophages to anti-inflammatory phenotype and promotes healing of infected tissue. This work provides a smart nanozyme with self-adaptive regulation of the antibiofilm activity and immune response by regulating ROS generation/elimination according to the different pathological microenvironments in implant infections during the different therapeutic stages.

Delayed implant-associated infection is an important challenge, as the treatment involves a high risk of implant replacement. Mussel-inspired antimicrobial coatings can be applied to coat a variety of implants in a facile way, but the adhesive 3,4-dihydroxyphenylalanine (DOPA) group is prone to oxidation. Therefore, an antibacterial polypeptide copolymer poly(Phe7-stat-Lys10)-b-polyTyr3 was designed to prepare the implant coating upon tyrosinase-induced enzymatic polymerization for preventing implant-associated infections. Both poly(Phe7-stat-Lys10) and polyTyr3 blocks have specific functions: the former provides intrinsic antibacterial activity with a low risk to induce antimicrobial resistance, and the latter is attachable to the surface of implants to rapidly generate an antibacterial coating by in situ injection of polypeptide copolymer since tyrosine could be oxidized to DOPA under catalyzation of skin tyrosinase. This polypeptide coating with excellent antibacterial effect and desirable biofilm inhibition activity is promising for broad applications in a multitude of biomedical materials to combat delayed infections.