BACKGROUND/AIM: This study investigated the therapeutic potential of lipophosphonoxin (LPPO), an antibacterial agent, loaded into polycaprolactone nanofiber dressings (NANO-LPPO) for full-thickness wound healing. Using a porcine model, we aimed to assess the impact of areal weight of the dressing (10, 20 and 30 g/m2) on wound-healing outcomes and validate findings from previous murine studies. MATERIALS AND METHODS: Full-thickness wounds were created on porcine skin and treated with the NANO-LPPO dressings of differing thickness. Positive control (Aquacel Ag+) and standard control (Jelonet) groups were included for comparison. Wound-healing progression was evaluated macroscopically and on the histological level. RESULTS: Macroscopic observations indicated no signs of infection in any group, with wounds covered by scabs by day 14. Thicker dressings (areal weights of 30 and 20 g/m2) demonstrated superior performance in promoting the formation of granulation tissue and healing compared to the thinner version (areal weight of 10 g/m2). LPPO-loading enhanced scaffold wettability and biodegradability without impairing healing outcomes. Both control groups exhibited similar healing characteristics. CONCLUSION: The findings underscore the importance of optimizing dressing thickness for effective wound healing. NANO-LPPO dressings exhibit translational potential as a therapeutic option for full-thickness wounds, warranting further preclinical and regulatory evaluation to support clinical application.

• Keywords
• Wound healing, active wound dressing, antibacterial agent, regeneration, repair, skin, wound treatment,
• MeSH
• Anti-Bacterial Agents pharmacology   administration & dosage   chemistry   MeSH
• Wound Healing * drug effects   MeSH
• Skin drug effects   pathology   MeSH
• Lipoxins * chemistry   pharmacology   administration & dosage   MeSH
• Disease Models, Animal MeSH
• Nanofibers * chemistry   MeSH
• Bandages * MeSH
• Polyesters * chemistry   MeSH
• Swine MeSH
• Animals MeSH
• Check Tag
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Anti-Bacterial Agents MeSH
• Lipoxins * MeSH
• polycaprolactone MeSH Browser
• Polyesters * MeSH

Today, when nanotechnological innovation, in particular, faces stringent regulations, the question arises concerning a tool that can quantify individual interventions and thus complement current knowledge in the diffusion theory of innovation. This paper examines the complex nature of innovation diffusion in a rapidly evolving technological environment. The research presents current knowledge in the field linking diffusion of innovation theory and the basic epidemiological model of SIR (Susceptible, Infected, Recovered). Epidemiological models, originally developed to study the spread of infectious diseases, offer intriguing parallels to innovation diffusion due to shared characteristics in propagation dynamics. Integrating the SIR epidemiological model into the current theoretical framework allows the SIR model to be considered as a tool capable of filling current gaps in the literature. Nanotechnological innovations are chosen because of their significant impact on society, which faces unique market entry challenges. Within the framework of high interdisciplinarity, nanotechnologies, like viruses, tend to 'mutate' into different industries where their 'infectivity' varies. The case of nanotechnology serves to illustrate the usefulness of the proposed model and shows how factors that influence the spread of viruses can similarly affect the adoption of technological innovations. Similar characteristics in the propagation framework between innovations and viruses can serve as one of many arguments for the use of the SIR model in this field. Using an integrative review, aspects that have the potential to add to the SIR model in the current literature are identified. By combining epidemiological findings with innovation theory, the paper contributes to a richer and more integrated understanding of the phenomena of diffusion of nanotechnological innovations. The motivation is to open a debate regarding the ability of the epidemiological model of SIR to reveal the impact of interventions affecting the diffusion of innovations.

• Keywords
• Bass model, Diffusion of innovation, Nanotechnology, SIR model,
• Publication type
• Journal Article MeSH
• Review MeSH

Agrimonia eupatoria L. (AE) has a rich tradition of use in wound healing improvement across various cultures worldwide. In previous studies, we revealed that Agrimonia eupatoria L. water extract (AE) possesses a rich polyphenolic composition, displaying remarkable antioxidant properties. Our investigations also demonstrated that lipophosphonoxin (LPPO) exhibited antibacterial efficacy in vitro while preserving the proliferation and differentiation of fibroblasts and keratinocytes. Building upon our prior findings, in this study, we intended to examine whether a combination of AE and LPPO could enhance skin wound healing while retaining antibacterial attributes. The antibacterial activity of AE/LPPO against Staphylococcus aureus was evaluated, alongside its effects on fibroblast-to-myofibroblast transition, the formation of extracellular matrix (ECM), and endothelial cells and keratinocyte proliferation/phenotype. We also investigated AE/LPPO's impact on TGF-β1 and VEGF-A signaling in keratinocytes/fibroblasts and endothelial cells, respectively. Additionally, wound healing progression in rats was examined through macroscopic observation and histological analysis. Our results indicate that AE/LPPO promotes myofibroblast-like phenotypic changes and augments ECM deposition. Clinically relevant, the AE/LPPO did not disrupt TGF-β1 and VEGF-A signaling and accelerated wound closure in rats. Notably, while AE and LPPO individually exhibited antibacterial activity, their combination did not lead to synergism, rather decreasing antibacterial activity, warranting further examination. These findings underscore substantial wound healing improvement facilitated by AE/LPPO, requiring further exploration in animal models closer to human physiology.

• Keywords
• extracellular matrix, phytotherapy, regeneration, repair, skin tissue,
• MeSH
• Agrimonia * chemistry   MeSH
• Anti-Bacterial Agents * pharmacology   chemistry   MeSH
• Fibroblasts drug effects   metabolism   MeSH
• Wound Healing * drug effects   MeSH
• Keratinocytes drug effects   MeSH
• Rats MeSH
• Humans MeSH
• Rats, Sprague-Dawley MeSH
• Cell Proliferation drug effects   MeSH
• Plant Extracts * pharmacology   chemistry   MeSH
• Staphylococcus aureus * drug effects   MeSH
• Transforming Growth Factor beta1 metabolism   MeSH
• Vascular Endothelial Growth Factor A metabolism   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Humans MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Anti-Bacterial Agents * MeSH
• Plant Extracts * MeSH
• Transforming Growth Factor beta1 MeSH
• Vascular Endothelial Growth Factor A MeSH

The presented work brings new knowledge in the field of spinning electrodes for AC‑electrospinning technology, which is used for producing nanofibrous structures using a solution of polyvinyl butyral. It presents new types of spinning weir‑electrodes and describes research on the influence of electrode design parameters on the stability of the spinning process and the productivity of nanofiber production. The multistage spinning electrode is presented in the ratio of stages one to five. Research is also focused on the effect of the parameters of the electric signal used as a source for the spinning electrode on spinning stability and productivity. Observed parameters were voltage level, frequency and shape such as sine wave, rectangle wave and modified sine wave. An analysis of the influence of the spinning conditions on the resulting nanofibrous structure was also performed by analyzing results gained by SEM; the defects were investigated mainly. The results of the research presented in the thesis open up new possibilities for follow-up research in the field of AC-electrospinning.

• Keywords
• AC electrospinning, Electric field, Electrospinning, Nanofibers, Spinning electrode,
• Publication type
• Journal Article MeSH

In the past few decades, society has faced rapid development and spreading of antimicrobial resistance due to antibiotic misuse and overuse and the immense adaptability of bacteria. Difficulties in obtaining effective antimicrobial molecules from natural sources challenged scientists to develop synthetic molecules with antimicrobial effect. We developed modular molecules named LEGO-Lipophosphonoxins (LEGO-LPPO) capable of inducing cytoplasmic membrane perforation. In this structure-activity relationship study we focused on the role of the LEGO-LPPO hydrophobic module directing the molecule insertion into the cytoplasmic membrane. We selected three LEGO-LPPO molecules named C9, C8 and C7 differing in the length of their hydrophobic chain and consisting of an alkenyl group containing one double bond. The molecule with the long hydrophobic chain (C9) was shown to be the most effective with the lowest MIC and highest perforation rate both in vivo and in vitro. We observed high antimicrobial activity against both G+ and G- bacteria with significant differences in LEGO-LPPOs mechanism of action on these two cell types. We observed a highly cooperative mechanism of LEGO-LPPO action on G- bacteria as well as on liposomes resembling G- bacteria. LEGO-LPPO action on G- bacteria was significantly slower compared to G+ bacteria suggesting the role of the outer membrane in affecting the LEGO-LPPOs perforation rate. This notion was supported by the higher sensitivity of the E. coli strain with a compromised outer membrane. Finally, we noted that the composition of the cytoplasmic membrane affects the activity of LEGO-LPPOs since the presence of phosphatidylethanolamine increases their membrane disrupting activity.

• Publication type
• Journal Article MeSH

Lipophosphonoxins (LPPOs) represent a new group of membrane-targeting antibiotics. Three generations of LPPOs have been described: First-generation LPPOs, second-generation LPPOs, and LEGO-LPPOs. All three generations have a similar mode of bactericidal action of targeting and disrupting the bacterial cytoplasmic membrane of prokaryotic cells, with limited effect on eukaryotic cells. First-generation LPPOs showed excellent bactericidal activity against Gram-positive species, including multiresistant strains. Second-generation LPPOs broaden the antibiotic effect also against Gram-negative bacteria. However, both first- and second-generation LPPOs lose their antibacterial activity in the presence of serum albumin. LEGO-LPPOs were found to be active against both Gram-positive and Gram-negative bacteria, have better selectivity as compared to first- and second-generation resistance to LEGO-LPPOs was also not observed, and are active even in the presence of serum albumin. Second-generation LPPOs have been studied as antimicrobial additives in bone cement and as nanofiber dressing components in the treatment of wound infections in mice. Second-generation LPPOs and LEGO-LPPOs were also tested to treat ex vivo simulated endodontic infections in dental root canals. The results of all these studies were encouraging and suggested further investigation of LPPOs in these indications. This paper aims to review and compile published data on LPPOs.

• Keywords
• LPPOs, Lipophosphonoxins, antibiotics, antimicrobial resistance,
• Publication type
• Journal Article MeSH
• Review MeSH

The alarming rise of bacterial antibiotic resistance requires the development of new compounds. Such compounds, lipophosphonoxins (LPPOs), were previously reported to be active against numerous bacterial species, but serum albumins abolished their activity. Here we describe the synthesis and evaluation of novel antibacterial compounds termed LEGO-LPPOs, loosely based on LPPOs, consisting of a central linker module with two attached connector modules on either side. The connector modules are then decorated with polar and hydrophobic modules. We performed an extensive structure-activity relationship study by varying the length of the linker and hydrophobic modules. The best compounds were active against both Gram-negative and Gram-positive species including multiresistant strains and persisters. LEGO-LPPOs act by first depleting the membrane potential and then creating pores in the cytoplasmic membrane. Importantly, their efficacy is not affected by the presence of serum albumins. Low cytotoxicity and low propensity for resistance development demonstrate their potential for therapeutic use.

• MeSH
• Albumins MeSH
• Anti-Bacterial Agents * chemistry   MeSH
• Cell Membrane MeSH
• Gram-Negative Bacteria MeSH
• Gram-Positive Bacteria * MeSH
• Microbial Sensitivity Tests MeSH
• Structure-Activity Relationship MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Albumins MeSH
• Anti-Bacterial Agents * MeSH