Bone healing is a complex cascade involving precisely coordinated spatiotemporal presentation of multiple growth factors (GFs), including osteogenic and angiogenic GFs, and each stage of bone healing requires varying types and content of GFs. In this study, we fabricated a composite nanocoating with tunable vascular endothelial growth factor (VEGF) and bone morphogenetic protein‐2 (BMP‐2) that was coated on the surface of a polydopamine (PDA)‐decorated tertiary calcium phosphate (TCP) scaffold using VEGF‐loaded chitosan/bovine serum albumin nanoparticles (CS/BSA‐NPs) and BMP‐2‐loaded poly‐L‐lysine/oxidized alginate nanoparticles (PLL/OALG‐NPs). It was found that VEGF could be efficiently released to promote vascularization in early bone repair stages due to the rapid biodegradation of CS/BSA‐NPs, while bone formation can be promoted by a sustained release of BMP‐2 from the slowly degrading PLL/OALG‐NPs. The composite coating and TCP scaffold can be conjugated due to the excellent adhesive property of PDA. The composite coating can achieve the rapid release of VEGF and sustained release of BMP‐2, which can activate GFs for accelerating bone healing.
Pulse lavage (PL) debridement and ultrasound are both known to be the treatment of biofilm-related periprosthetic joint infection (PJI). However, the efficacy of these in combination is unknown in eradicating biofilm from the orthopaedic metal implant surface. This study was conducted to understand the efficacy of PL and ultrasound in combination in eradicating bacterial biofilms on titanium alloy in vitro. Biofilms of Staphylococcus aureus strains were grown on titanium alloy coupons for 24 h. Then, the coupons were taken to each treatment group: (i) debrided with PL, (ii) exposed to ultrasound, or (iii) exposed to both. An untreated biofilm was set as a control group. Viable plate count and confocal microscopy using live/dead staining was used to measure the amount of biofilm. Viable plate count showed an approximate two-log reduction in CFU/cm2 in PL alone, from an initial cell count on the mental surface of approximately 109 CFU/cm2. The ultrasound caused an approximate seven-log reduction, and the combination group eradicated viable biofilm bacteria completely. Confocal imaging corroborated the CFU data. Our results indicate that PL and ultrasound both are remarkably in eradicating biofilm, and the combination of PL and ultrasound is more effective than alone in reducing biofilm.
Aspergillus fumigatus is a well-known opportunistic pathogen that causes invasive aspergillosis (IA) infections, which have high mortality rates in immunosuppressed individuals. Long-term antifungal drug azole use in clinical treatment and agriculture results in loss of efficacy or drug resistance. Drug resistance is related to cellular metabolites and the corresponding gene transcription. In this study, through untargeted metabolomics and transcriptomics under itraconazole (ITC) treatment, we identified two plasma membrane-localized polyamine regulators tpo3 and dur3, which were important for polyamine homeostasis and susceptibility to ITC in A. fumigatus. In the absence of tpo3 and/or dur3, the levels of cytoplasmic polyamines had a moderate increase, which enhanced the tolerance of A. fumigatus to ITC. In comparison, overexpression of tpo3 or dur3 induced a drastic increase in polyamines, which increased the sensitivity of A. fumigatus to ITC. Further analysis revealed that polyamines concentration-dependently affected the susceptibility of A. fumigatus to ITC by scavenging reactive oxygen species (ROS) at a moderate concentration and promoting the production of ROS at a high concentration rather than regulating drug transport. Moreover, inhibition of polyamine biosynthesis reduced the intracellular polyamine content, resulted in accumulation of ROS and enhanced the antifungal activity of ITC. Interestingly, A. fumigatus produces much lower levels of ROS under voriconazole (VOC) treatment than under ITC-treatment. Accordingly, our study established the link among the polyamine regulators tpo3 and dur3, polyamine homeostasis, ROS content, and ITC susceptibility in A. fumigatus.
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