Fibrin Matrices as (Injectable) Biomaterials: Formation, Clinical Use, and Molecular Engineering

This review focuses on fibrin, starting from biological mechanisms (its production from fibrinogen and its enzymatic degradation), through its use as a medical device and as a biomaterial, and finally discussing the techniques used to add biological functions and/or improve its mechanical performance through its molecular engineering. Fibrin is a material of biological (human, and even patient's own) origin, injectable, adhesive, and remodellable by cells; further, it is nature's most common choice for an in situ forming, provisional matrix. Its widespread use in the clinic and in research is therefore completely unsurprising. There are, however, areas where its biomedical performance can be improved, namely achieving a better control over mechanical properties (and possibly higher modulus), slowing down degradation or incorporating cell‐instructive functions (e.g., controlled delivery of growth factors). The authors here specifically review the efforts made in the last 20 years to achieve these aims via biomimetic reactions or self‐assembly, as much via formation of hybrid materials

Effective linear damping and stiffness coefficients of nonlinear systems for design spectrum based analysis

A stochastic approach for obtaining reliable estimates of the peak response of nonlinear systems to excitations specified via a design seismic spectrum is proposed. This is achieved in an efficient manner without resorting to numerical integration of the governing nonlinear equations of motion. First, a numerical scheme is utilized to derive a power spectrum which is compatible in a stochastic sense with a given design spectrum. This power spectrum is then treated as the excitation spectrum to determine effective damping and stiffness coefficients corresponding to an equivalent linear system (ELS) via a statistical linearization scheme. Further, the obtained coefficients are used in conjunction with the (linear) design spectrum to estimate the peak response of the original nonlinear systems. The cases of systems with piecewise linear stiffness nonlinearity, along with bilinear hysteretic systems are considered. The seismic severity is specified by the elastic design spectrum prescribed by the European aseismic code provisions (EC8). Monte Carlo simulations pertaining to an ensemble of nonstationary EC8 design spectrum compatible accelerograms are conducted to confirm that the average peak response of the nonlinear systems compare reasonably well with that of the ELS, within the known level of accuracy furnished by the statistical linearization method. In this manner, the proposed approach yields ELS which can replace the original nonlinear systems in carrying out computationally efficient analyses in the initial stages of the aseismic design of structures under severe seismic excitations specified in terms of a design spectrum

Novel Cold-Adapted Lipase from Marine Plankton, Salpa thompsoni

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An Instrumented Cochlea Model for the Evaluation of Cochlear Implant Electrical Stimulus Spread.

Cochlear implants use electrical stimulation of the auditory nerve to restore the sensation of hearing to deaf people. Unfortunately, the stimulation current spreads extensively within the cochlea, resulting in "blurring" of the signal, and hearing that is far from normal. Current spread can be indirectly measured using the implant electrodes for both stimulating and sensing, but this provides incomplete information near the stimulating electrode due to electrode-electrolyte interface effects. Here, we present a 3D-printed "unwrapped" physical cochlea model with integrated sensing wires. We integrate resistors into the walls of the model to simulate current spread through the cochlear bony wall, and "tune" these resistances by calibration with an in-vivo electrical measurement from a cochlear implant patient. We then use this model to compare electrical current spread under different stimulation modes including monopolar, bipolar and tripolar configurations. Importantly, a trade-off is observed between stimulation amplitude and current focusing among different stimulation modes. By combining different stimulation modes and changing intracochlear current sinking configurations in the model, we explore this trade-off between stimulation amplitude and focusing further. These results will inform clinical strategies for use in delivering speech signals to cochlear implant patients

Adenovirus 5 recovery using nanofiber ion‐exchange adsorbents

This is an accepted manuscript of an article published by Wiley in Biotechnology and Bioengineering on 28/03/2019, available online: https://doi.org/10.1002/bit.26972 The accepted version of the publication may differ from the final published version.Viral vectors such as adenovirus have successful applications in vaccines and gene therapy but the manufacture of the high‐quality virus remains a challenge. It is desirable to use the adsorption‐based chromatographic separations that so effectively underpin the therapeutic protein manufacture. However fundamental differences in the size and stability of this class of product mean it is necessary to revisit the design of sorbent's morphology and surface chemistry. In this study, the behaviour of a cellulose nanofiber ion‐exchange sorbent derivatised with quaternary amine ligands at defined densities is characterised to address this. This material was selected as it has a large accessible surface area for viral particles and rapid process times. Initially, the impact of surface chemistry on infective product recovery using low (440 µmol/g), medium (750 µmol/g), and high (1029 µmol/g) ligand densities is studied. At higher densities product stability is reduced, this effect increased with prolonged adsorption durations of 24 min with just ~10% loss at low ligand density versus ~50% at high. This could be mitigated by using a high flow rate to reduce the cycle time to ~1 min. Next, the impact of ligand density on the separation's resolution was evaluated. Key to understanding virus quality is the virus particle: infectious virus particle ratio. It was found this parameter could be manipulated using ligand density and elution strategy. Together this provides a basis for viral vector separations that allows for their typically low titres and labile nature by using high liquid velocity to minimise both load and on‐column times while separating key product and process‐related impurities.This study was supported by the UK Engineering and Physical Sciences Research Council (EPSRC) grant EP/L01520X/1, and Puridify (now part of GE Healthcare), in conjunction with grant EP/N013395/1.Published versio

A novel stochastic linearization framework for seismic demand estimation of hysteretic MDOF systems subject to linear response spectra

This paper proposes a novel computationally economical stochastic dynamics framework to estimate the peak inelastic response of yielding structures modelled as nonlinear multi degreeof-freedom (DOF) systems subject to a given linear response spectrum defined for different damping ratios. This is accomplished without undertaking nonlinear response history analyses (RHA) or, to this effect, constructing an ensemble of spectrally matched seismic accelerograms. The proposed approach relies on statistical linearization and enforces pertinent statistical conditions to decompose the inelastic d-DOF system into d linear single DOF oscillators with effective linear properties (ELPs): natural frequency and damping ratio. Each such oscillator is subject to a different stationary random process compatible with the excitation response spectrum with damping ratio equal to the oscillator effective critical damping ratio. This equality is achieved through a small number of iterations to a pre-specified tolerance, while peak inelastic response estimates for all DOFs of interest are obtained by utilization of the excitation response spectrum in conjunction with the ELPs. The applicability of the proposed framework is numerically illustrated using a 3-storey Bouc-Wen hysteretic frame structure exposed to the Eurocode 8 elastic response spectrum. Nonlinear RHA involving a large ensemble of non-stationary Eurocode 8 spectrum compatible accelerograms is conducted to assess the accuracy of the proposed approach in a Monte Carlo-based context. It is found that the novel feature of iterative matching between the excitation response spectrum damping ratio and the ELP damping ratio reduces drastically the error of the estimates (i.e., by an order of magnitude) obtained by non-iterative application of the framework