The Host Immune Response to Tissue-Engineered Organs: Current Problems and Future Directions

As the global health burden of chronic disease increases, end-stage organ failure has become a costly and intractable problem. De novo organ creation is one of the long-term goals of the medical community. One of the promising avenues is that of tissue engineering: the use of biomaterials to create cells, structures, or even whole organs. Tissue engineering has emerged from its nascent stage, with several proof-of-principle trials performed across various tissue types. As tissue engineering moves from the realm of case trials to broader clinical study, three major questions have emerged: (1) Can the production of biological scaffolds be scaled up accordingly to meet current and future demands without generating an unfavorable immune response? (2) Are biological scaffolds plus or minus the inclusion of cells replaced by scar tissue or native functional tissue? (3) Can tissue-engineered organs be grown in children and adolescents given the different immune profiles of children? In this review, we highlight current research in the immunological response to tissue-engineered biomaterials, cells, and whole organs and address the answers to these questions

Machine Learning Enables Prompt Prediction of Hydration Kinetics of Multicomponent Cementitious Systems

Carbonaceous (e.g., limestone) and aluminosilicate (e.g., calcined clay) mineral additives are routinely used to partially replace ordinary portland cement in concrete to alleviate its energy impact and carbon footprint. These mineral additives—depending on their physicochemical characteristics—alter the hydration behavior of cement; which, in turn, affects the evolution of microstructure of concrete, as well as the development of its properties (e.g., compressive strength). Numerical, reaction-kinetics models—e.g., phase boundary nucleation-and-growth models; which are based partly on theoretically-derived kinetic mechanisms, and partly on assumptions—are unable to produce a priori prediction of hydration kinetics of cement; especially in multicomponent systems, wherein chemical interactions among cement, water, and mineral additives occur concurrently. This paper introduces a machine learning-based methodology to enable prompt and high-fidelity prediction of time-dependent hydration kinetics of cement, both in plain and multicomponent (e.g., binary; and ternary) systems, using the system’s physicochemical characteristics as inputs. Based on a database comprising hydration kinetics profiles of 235 unique systems—encompassing 7 synthetic cements and three mineral additives with disparate physicochemical attributes—a random forests (RF) model was rigorously trained to establish the underlying composition-reactivity correlations. This training was subsequently leveraged by the RF model: to predict time-dependent hydration kinetics of cement in new, multicomponent systems; and to formulate optimal mixture designs that satisfy user-imposed kinetics criteria

Serum levels of matrix metalloproteinases-2 and-9 and their tissue inhibitors in inflammatory neuromuscular disorders

We monitored serum levels of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) before and during intravenously applied immunoglobulin (IVIG) therapy in 33 patients with chronic immune-mediated neuropathies and myopathies and 15 controls. Baseline MMP-2 and TIMP-2 serum levels were lower and MMP-9 and TIMP-1 serum levels higher in all patients compared to age-matched controls. Eight days after IVIG treatment, MMP-2, TIMP-2, and TIMP-1 serum levels increased, while MMP-9 serum levels decreased, indicating tissue repair. After 60 days, MMP-9 levels increased, MMP-2 approached normal levels, while TIMP-1 and TIMP-2 serum levels were below day 8 levels, indicating relapsing tissue damage. Comparing the MMP/TIMP results with the clinical courses, IVIG treatment tended to change MMP/TIMP levels in a way that paralleled clinical improvement and relapse. In sum, during a distinct time period, IVIG therapy seems to be able to modulate VIMP-mediated tissue repair. Copyright (c) 2006 S. Karger AG, Basel

Structure-property and composition-property relationships for poly(ethylene terephthalate) surfaces modified by helium plasma-based ion implantation

The surfaces of untreated and helium plasma-based ion implantation (He PBII) treated poly(ethylene terephthalate) (PET) samples were characterised by reflectance colorimetry, contact angle studies and measurements of surface electrical resistance. The results were related to the structural and compositional data obtained by the authors earlier on parallel samples by XPS and Raman spectroscopy. Inverse correlations between lightness and ID/IG ratio and between chroma and ID/IG ratio were obtained, suggesting that the PBII-treated PET samples darken and their colourfulness decreases with the increase of the portion of aromatic sp2 carbon rings in the chemical structure of the modified layer. Direct correlation between water contact angle and the ID/IG ratio and inverse correlations between surface energy and ID/IG ratio and between dispersive component of surface energy and ID/IG ratio were found, reflecting that surface wettability, surface energy and its dispersive component decrease with the formation of surface structure, characterised again by enhanced portion of aromatic sp2 carbon rings. The surface electrical resistance decreased with the increase of the surface C-content determined by XPS and also with the increase of the surface concentration of conjugated double bonds, reflected by the increase of the pi-pi* shake-up satellite of the C 1s peak

Exploring multistep continuous-flow hydrosilylation reactions catalyzed by tris(pentafluorophenyl)borane

Exploring the combination of continuous‐flow processes with the boron Lewis acid catalyzed hydrosilylation of aldehydes and ketones has delivered a robust and generally applicable reaction protocol. Notably this approach permits ready access to high temperatures and pressures and thus allows improved reactivity of substrates that were previously recalcitrant under the traditional approach. Efforts to quench the output from the flow reactor with water showed surprising tolerance leading to the application of continuous‐flow systems in multistep imine formation/hydrosilylation processes to generate the corresponding secondary amines from their aldehyde and aniline precursors

The effect of grain size on electrical transport and magnetic properties of La0.9Te0.1MnO3

The effect of grain size on structural, magnetic and transport properties in electron-doped manganites La0.9Te0.1MnO3 has been investigated. All samples show a rhombohedral structure with the space group at room temperature. It shows that the Mn-O-Mn bond angle decreases and the Mn-O bond length increases with the increase of grain size. All samples undergo paramagnetic (PM)-ferromagnetic (FM) phase transition and an interesting phenomenon that both magnetization and the Curie temperature decrease with increasing grain size is observed, which is suggested to mainly originate from the increase of the Mn-O bond length . Additionally, obviously increases with decreasing grain size due to the increase of both the height and width of tunneling barriers with decreasing the grain size. The results indicate that both the intrinsic colossal magnetoresistance (CMR) and the extrinsic the extrinsic interfacial magnetoresistance (IMR) can be effectively tuned in La0.9Te0.1MnO3 by changing grain size.Comment: 15 pages,4 figures. Solid state communications 132(2004)83-8

Conserving, Distributing and Managing Genetically Modified Mouse Lines by Sperm Cryopreservation

Sperm from C57BL/6 mice are difficult to cryopreserve and recover. Yet, the majority of genetically modified (GM) lines are maintained on this genetic background.Reported here is the development of an easily implemented method that consistently yields fertilization rates of 70+/-5% with this strain. This six-fold increase is achieved by collecting sperm from the vas deferens and epididymis into a cryoprotective medium of 18% raffinose (w/v), 3% skim milk (w/v) and 477 microM monothioglycerol. The sperm suspension is loaded into 0.25 mL French straws and cooled at 37+/-1 degrees C/min before being plunged and then stored in LN(2). Subsequent to storage, the sperm are warmed at 2,232+/-162 degrees C/min and incubated in in vitro fertilization media for an hour prior to the addition of oocyte cumulus masses from superovulated females. Sperm from 735 GM mouse lines on 12 common genetic backgrounds including C57BL/6J, BALB/cJ, 129S1/SvImJ, FVB/NJ and NOD/ShiLtJ were cryopreserved and recovered. C57BL/6J and BALB/cByJ fertilization rates, using frozen sperm, were slightly reduced compared to rates involving fresh sperm; fertilization rates using fresh or frozen sperm were equivalent in all other lines. Developmental capacity of embryos produced using cryopreserved sperm was equivalent, or superior to, cryopreserved IVF-derived embryos.Combined, these results demonstrate the broad applicability of our approach as an economical and efficient option for archiving and distributing mice

The host metabolite D-serine contributes to bacterial niche specificity through gene selection

Escherichia coli comprise a diverse array of both commensals and niche-specific pathotypes. The ability to cause disease results from both carriage of specific virulence factors and regulatory control of these via environmental stimuli. Moreover, host metabolites further refine the response of bacteria to their environment and can dramatically affect the outcome of the host–pathogen interaction. Here, we demonstrate that the host metabolite, D-serine, selectively affects gene expression in E. coli O157:H7. Transcriptomic profiling showed exposure to D-serine results in activation of the SOS response and suppresses expression of the Type 3 Secretion System (T3SS) used to attach to host cells. We also show that concurrent carriage of both the D-serine tolerance locus (dsdCXA) and the locus of enterocyte effacement pathogenicity island encoding a T3SS is extremely rare, a genotype that we attribute to an ‘evolutionary incompatibility’ between the two loci. This study demonstrates the importance of co-operation between both core and pathogenic genetic elements in defining niche specificity

The effect of oxygen stoichiometry on electrical transport and magnetic properties of La0.9Te0.1MnOy

The effect of the variation of oxygen content on structural, magnetic and transport properties in the electron-doped manganites La0.9Te0.1MnOy has been investigated. All samples show a rhombohedral structure with the space group . The Curie temperature decreases and the paramagnetic-ferromagnetic (PM-FM) transition becomes broader with the reduction of oxygen content. The resistivity of the annealed samples increases slightly with a small reduction of oxygen content. Further reduction in the oxygen content, the resistivity maximum increases by six orders of magnitude compared with that of the as-prepared sample, and the r(T) curves of samples with y = 2.86 and y = 2.83 display the semiconducting behavior () in both high-temperature PM phase and low-temperature FM phase, which is considered to be related to the appearance of superexchange ferromagnetism (SFM) and the localization of carriers. The results are discussed in terms of the combined effects of the increase in the Mn2+/(Mn2++Mn3+) ratio, the partial destruction of double exchange (DE) interaction, and the localization of carriers due to the introduction of oxygen vacancies in the Mn-O-Mn network.Comment: 20 pages, 8 figure

Use of Zebrafish to Probe the Divergent Virulence Potentials and Toxin Requirements of Extraintestinal Pathogenic Escherichia coli

Extraintestinal pathogenic E. coli (ExPEC) cause an array of diseases, including sepsis, neonatal meningitis, and urinary tract infections. Many putative virulence factors that might modulate ExPEC pathogenesis have been identified through sequencing efforts, epidemiology, and gene expression profiling, but few of these genes have been assigned clearly defined functional roles during infection. Using zebrafish embryos as surrogate hosts, we have developed a model system with the ability to resolve diverse virulence phenotypes and niche-specific restrictions among closely related ExPEC isolates during either localized or systemic infections. In side-by-side comparisons of prototypic ExPEC isolates, we observed an unexpectedly high degree of phenotypic diversity that is not readily apparent using more traditional animal hosts. In particular, the capacity of different ExPEC isolates to persist and multiply within the zebrafish host and cause disease was shown to be variably dependent upon two secreted toxins, α-hemolysin and cytotoxic necrotizing factor. Both of these toxins appear to function primarily in the neutralization of phagocytes, which are recruited in high numbers to sites of infection where they act as an essential host defense against ExPEC as well as less virulent E. coli strains. These results establish zebrafish as a valuable tool for the elucidation and functional analysis of both ExPEC virulence factors and host defense mechanisms