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Jones, A.-A. D.

Publications and source records attributed to Jones, A.-A. D..

6 recordsLinked to original sources

Nanocellulose hydrogels as bio-interface analogs for studying nanomaterial transport and accumulation

Nanomaterials have been proposed as drug delivery vehicles to enhance targeting and efficiency of traditional and novel therapeutics and have subsequently been studied for potential ecotoxicity. Previous studies have identified size, surface charge, and volume exclusion as factors that influence nanomaterial diffusion and retention. However, there is little accepted or successful quantification of how these parameters influence nanomaterial penetration relative to biological adaptation and biological response. Part of the challenge is the response of living biological interfaces to many of these nanomaterial delivery vehicles and nanosized drugs. This study aimed to emulate key physicochemical barriers to diffusion found in living biomaterials by developing a tunable, synthetic hydrogel. Through the controlled exposure of 150 kDa and 2 MDa nanodextrans with neutral and negative surface charge, we evaluated the systems ability to emulate three core physicochemical features often implicated in biofilm-associated transport resistance: size exclusion, charge interactions, and volume exclusion. We demonstrated a 30% statistically significant decrease in partition coefficients for 2 MDa nanodextran from 150 kDa nanodextran, confirming the ability of the nanocellulose-based microcaps to mimic the permeability of hydrated biomaterial matrices. These findings reflect patterns observed in, for example, living biofilm studies, where size-based diffusion hinderance is commonly reported, but charge-based interaction and volume exclusion are more context-dependent. This controllable system can be coupled with in silico modeling to understand interfacial transport phenomena for nanomaterial-biomaterial interactions. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=91 SRC="FIGDIR/small/703274v1_ufig1.gif" ALT="Figure 1"> View larger version (21K): org.highwire.dtl.DTLVardef@13c1a34org.highwire.dtl.DTLVardef@dc6c5borg.highwire.dtl.DTLVardef@14dcbd4org.highwire.dtl.DTLVardef@80f70c_HPS_FORMAT_FIGEXP M_FIG C_FIG

biophysics↗

In vitro evaluation of Escherichia coli and Staphylococcus aureus translocation in 3D printed material

Vascular graft infection is a rare but life threating condition, primarily occurring after 30 days post-surgery. Meta-analysis has shown that antimicrobial coatings on graft materials do not prevent these infections. Moreover, infection still occurs even though studies have also shown that there is no bacterial proliferation on or bacterial penetration of common vascular graft material. The time frame of infection, meta-analysis, and in situ studies suggest that bacteria present at the suture site are introduced into the surrounding tissue or that systemically circulating bacteria may be surviving, proliferating, diffusing slowly, and evading host immune defense in synthetic vascular grafts. De novo vascular graft materials, such as tissue-engineered vascular graft material and decellularized vasculature may provide an in situ platform for studying survival, proliferation, and diffusion in tissue and tissue-like materials. In this study, we use confocal microscopy to image penetration depth of bacteria over time as a proxy for diffusion of Staphylococcus aureus and Escherichia coli into alginate, GelMA, and decellularized porcine vascular tissue. We quantified viable bacteria breakthrough as a function of biomaterial type. We found penetration depth over time was similar in all three biomaterials, however E. coli broke through much less from tissue than from engineered materials, while S. aureus had higher breakthrough in the GelMa but otherwise equal rates. These results point to the possibility of interstitial growth control relative to surface coatings as a future target for engineering infection resistance in engineered vascular grafts. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=140 SRC="FIGDIR/small/703277v1_ufig1.gif" ALT="Figure 1"> View larger version (34K): org.highwire.dtl.DTLVardef@193760org.highwire.dtl.DTLVardef@1829d6corg.highwire.dtl.DTLVardef@2d4535org.highwire.dtl.DTLVardef@1ab869_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗

Heterogenous Biofilm Mass-Transport Model Replicates Periphery Sequestration of Antibiotics in P. aeruginosa PAO1 Microcolonies

1A spatiotemporal model for antibiotic accumulation in bacterial biofilm microcolonies which leverages heterogenous porosity and attachment site profiles replicated the periphery sequestration phenomena reported in prior experimental studies on Pseudomonas aeruginosa PAO1 biofilm cell clusters. These P. aeruginosa cell clusters are in vitro models of the chronic P. aeruginosa infections found in adult cystic fibrosis patients, which display resistance to antibiotic treatments, leading to exacerbated morbidity and mortality. This resistance has been partially attributed to periphery sequestration, where antibiotics are unable to penetrate biofilm cell clusters. The underlying physical phenomena driving this periphery sequestration have not been definitively established. This paper introduces mathematical models to account for two proposed physical phenomena driving periphery sequestration: biofilm matrix attachment and volume-exclusion due to variable biofilm porosity. An antibiotic accumulation model which incorporated these phenomena was able to better fit observed periphery sequestration data compared to previous models.

biophysics↗

Surface Energy and Viscoelastic Characteristics of Staphylococcus epidermidis and Cutibacterium acnes Biofilm on Commercial Skin Constructs versus agar

Biofilms are recalcitrant to both study and infectious disease treatment as it requires not only the study or management of single organism behavior, but also many dynamical interactions including but not limited to bacteria-bacteria, bacteria-host, bacteria-nutrients, and bacteria-material across multiple time scales. This study performs comparative and quantitative research of two materials used in biofilm research, TSA agar and skin epidermal, to reveal how adhesion effects viscoelastic properties of biofilms at long time scales. We show that the host surface stressors, such as wettability and surface energy, impact the biofilms mechanical integrity and viscoelastic properties. While it is known that the bacteria-material interface influences initial biofilm formation and external stress influences mature biofilm function, this study examines the influence of the bacteria-material interface on mature biofilms. These mechanical viscoelastic properties have the potential to determine metabolite and pathogenesis pathways which means that the platform researchers use to study impacts the outcome.

microbiology↗

Statistical classification of dynamic bacterial growth with sub-inhibitory concentrations of nanoparticles and its implications for disease treatment

Nanoparticles are promising alternatives to antibiotics since nanoparticles are easy to manufacture, non-toxic, and do not promote resistance. Nanoparticles act via physical disruption of the bacterial membrane and/or the generation of high concentrations of reactive-oxygen species locally. Potential for physical disruption of the bacterial membrane may be quantified by free energy methods, such as the extended Derjuan-Landau-Verwey-Overbeek theory, which predicts the initial surface-material interactions. The generation of reactive-oxygen species may be quantified using enthalpies of formation to predict minimum inhibitory concentrations. Neither of these two quantitative structure-activity values describes the dynamic, in situ behavioral changes in the bacterias struggle to survive. In this paper, borrowing parameters from logistic, oscillatory, and diauxic growth models, we use principal component analysis and agglomerative hierarchical clustering to classify survival modes across nanoparticle types and concentrations. We compare the growth parameters of 170 experimental interactions between nanoparticles and bacteria. The bacteria studied include Escherichia coli, Staphylococcus aureus, Methicillin-Resistant Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, and Helicobacter pylori, and were tested across multiple concentrations of liposomal drug delivery systems, amphiphilic peptide, and silver and selenium nanoparticles. Clustering reveals specific pairs of bacteria and nanoparticles where the nanoparticle induced growth dynamics could potentially spread the infection through the development of resistance and tolerance. This rapid screening also shows that bacteria generated nanoparticles do not induce growth modes indicative of the development of resistance. This methodology can be used to rapidly screen for novel therapeutics that do not induce resistance before using more robust intracellular content screening. This methodology can also be used as a quality check on batch manufactured nanoparticles.

microbiology↗

Shear stress mediates metabolism and growth in electroactive biofilms

Electroactive bacteria such as Geobacter sulfurreducens and Shewanella onedensis produce electrical current during their respiration; this has been exploited in bioelectrochemical systems. These bacteria form thicker biofilms and stay more active than soluble-respiring bacteria biofilms because their electron acceptor is always accessible. In bioelectrochemical systems such as microbial fuel cells, corrosion-resistant metals uptake current from the bacteria, producing power. While beneficial for engineering applications, collecting current using corrosion resistant metals induces pH stress in the biofilm, unlike the naturally occurring process where a reduced metal combines with protons released during respiration. To reduce pH stress, some bioelectrochemical systems use forced convection to enhance mass transport of both nutrients and byproducts; however, biofilms small pore size limits convective transport, thus, reducing pH stress in these systems remains a challenge. Understanding how convection is necessary but not sufficient for maintaining biofilm health requires decoupling mass transport from momentum transport (i.e. fluidic shear stress). In this study we use a rotating disc electrode to emulate a practical bioelectrochemical system, while decoupling mass transport from shear stress. This is the first study to isolate the metabolic and structural changes in electroactive biofilms due to shear stress. We find that increased shear stress reduces biofilm development time while increasing its metabolic rate. Furthermore, we find biofilm health is negatively affected by higher metabolic rates over long-term growth due to the biofilms memory of the fluid flow conditions during the initial biofilm development phases. These results not only provide guidelines for improving performance of bioelectrochemical systems, but also reveal features of biofilm behavior. Results of this study suggest that optimized reactors may initiate operation at high shear to decrease development time before decreasing shear for steady-state operation. Furthermore, this biofilm memory discovered will help explain the presence of channels within biofilms observed in other studies.

microbiology↗