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Register a new userPhotodynamically Active Electrospun Fibres for Antibiotic-Free Infection Control
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Antimicrobial biomaterials are critical to aid in the regeneration of oral soft tissue and prevent or treat localised bacterial infections. With the rising trend in antibiotic resistance, there is a pressing clinical need for new antimicrobial chemistries and biomaterial design approaches enabling on-demand activation of antibiotic-free antimicrobial functionality following an infection that are environment-friendly, flexible and commercially-viable. This study explores the feasibility of integrating a bioresorbable electrospun polymer scaffold with localised antimicrobial photodynamic therapy (aPDT) capability. To enable aPDT, we encapsulated a photosensitiser (PS) in polyester fibres in the PS inert state, so that the antibacterial function would be activated on-demand via a visible light source. Fibrous scaffolds were successfully electrospun from FDA-approved polyesters, either poly(epsilon-caprolactone (PCL) or poly[(rac-lactide)-co-glycolide] (PLGA) with encapsulated PS (either methylene blue (MB) or erythrosin B (ER)). The electrospun fibres achieved an ~100 wt.% loading efficiency of PS, which significantly increased their tensile modulus and reduced their average fibre diameter and pore size with respect to PS-free controls. In vitro, PS release varied between a burst release profile to limited release within 100 hours depending on the selected scaffold formulation. Exposure of PS-encapsulated PCL fibres to visible light successfully led to at least a 1 log reduction in E. coli viability after 60 minutes of light exposure whereas PS-free electrospun controls did not inactive microbes. This study successfully demonstrates the significant potential of PS-encapsulated electrospun fibres as photodynamically active biomaterial for antibiotic-free infection control.
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Bone regeneration is a clinical challenge that requires multiple approaches. Sometimes, it also includes the development of new osteogenic and antibacterial biomaterials to treat the occurrence of possible infection processes derived from surgery. This study evaluates the antibacterial properties of meso-macroporous scaffolds coated with gelatin and based on a bioactive glass and after being doped with 4% ZnO (4ZN-GE) and loaded with saturated and minimally inhibitory concentrations of one of the antibiotics levofloxacin (LEVO), vancomycin (VANCO), rifampicin (RIFAM) or gentamicin (GENTA). After the physicochemical characterization of the materials, inorganic ion and antibiotic release studies were performed from the scaffolds. In addition, molecular modeling allowed the determination of electrostatic potential density maps and hydrogen bonds of the antibiotics and the glass matrix. In vitro antibacterial studies (in plankton, inhibition halos and biofilm destruction) with S. aureus and E. coli as model bacteria showed a synergistic effect of zinc ions and antibiotics. The effect was especially noticeable in planktonic cultures of S. aureus with 4ZN-GE scaffolds loaded with VANCO, LEVO or RIFAM and in cultures of E. coli with LEVO or GENTA. Furthermore, S. aureus biofilms were completely destroyed by 4ZN-GE scaffolds loaded with VANCO, LEVO or RIFAM and total destruction of E. coli biofilm was achieved with 4ZN-GE scaffolds loaded with GENTA or LEVO. This approach could be an important step in the fight against microbial resistance and provide much needed options for the treatment of bone infection.
It is now evident that the commonly accepted strategy for treatment of HIV/AIDS by highly active antiretroviral therapy (HAART) will not lead to eradication of HIV in a reasonable time. This is straightforward from the typical exponential viral load decay upon treatment revealing initial considerable but incomplete reduction of plasma HIV RNA with subsequent low level HIV persistence even in patients on effective antiretroviral therapy. Here we show that the viral load follows a simple zero trend linear regression line under different treatment approach recently proposed by us. This unambiguously indicates a whole body HIV eradication in reasonable time.
We describe reshaping of active textiles actuated by bending of Janus fibres comprising both active and passive components. A great variety of shapes, determined by minimising the overall energy of the fabric, can be produced by varying bending directions determined by the orientation of Janus fibres. Under certain conditions, alternative equilibrium states, one absolutely stable and the other metastable coexist, and their relative energy may flip its sign as system parameters, such as the extension upon actuation, change. A snap-through reshaping in a specially structured textile reproduces the Venus flytrap effect.
Simple ideas, endowed from the mathematical theory of control, are used in order to analyze in general grounds the human immune system. The general principles are minimization of the pathogen load and economy of resources. They should constrain the parameters describing the immune system. In the simplest linear model, for example, where the response is proportional to the load, the annihilation rate of pathogens in any tissue should be greater than the pathogens average rate of growth. When nonlinearities are added, a reference value for the number of pathogens is set, and a stability condition emerges, which relates strength of regular threats, barrier height and annihilation rate. The stability condition allows a qualitative comparison between tissues. On the other hand, in cancer immunity, the linear model leads to an expression for the lifetime risk, which accounts for both the effects of carcinogens (endogenous or external) and the immune response.
We study the early stages of viral infection, and the distribution of times to obtain a persistent infection. The virus population proliferates by entering and reproducing inside a target cell until a sufficient number of new virus particles are released via a burst, with a given burst size distribution, which results in the death of the infected cell. Starting with a 2D model describing the joint dynamics of the virus and infected cell populations, we analyze the corresponding master equation using the probability generating function formalism. Exploiting time-scale separation between the virus and infected cell dynamics, the 2D model can be cast into an effective 1D model. To this end, we solve the 1D model analytically for a particular choice of burst size distribution. In the general case, we solve the model numerically by performing extensive Monte-Carlo simulations, and demonstrate the equivalence between the 2D and 1D models by measuring the Kullback-Leibler divergence between the corresponding distributions. Importantly, we find that the distribution of infection times is highly skewed with a fat exponential right tail. This indicates that there is non-negligible portion of individuals with an infection time, significantly longer than the mean, which may have implications on when HIV tests should be performed.
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