A three-phase tessellation: solution and effective properties

Two-dimensional, doubly periodic, three-phase structures are considered in the situation where mean fluxes are applied across the structure. The approach is to use complex variables, and to use a mapping that reduces the doubly periodic problem to a much simpler one involving joined sectors. This is a model composite structure in electrostatics (and mathematically analogous areas such as porous media, anti-plane elasticity, heat conduction), and we find various effective parameters and investigate limiting cases. The structure is also amenable to asymptotic methods in the case of highly varying composition and we provide these solutions, partly as a check upon our analysis, and partly as they are useful in their own right

High-frequency homogenization for periodic media

This article is available open access through the publisher’s website at the link below. Copyright @ 2010 The Royal Society.An asymptotic procedure based upon a two-scale approach is developed for wave propagation in a doubly periodic inhomogeneous medium with a characteristic length scale of microstructure far less than that of the macrostructure. In periodic media, there are frequencies for which standing waves, periodic with the period or double period of the cell, on the microscale emerge. These frequencies do not belong to the low-frequency range of validity covered by the classical homogenization theory, which motivates our use of the term ‘high-frequency homogenization’ when perturbing about these standing waves. The resulting long-wave equations are deduced only explicitly dependent upon the macroscale, with the microscale represented by integral quantities. These equations accurately reproduce the behaviour of the Bloch mode spectrum near the edges of the Brillouin zone, hence yielding an explicit way for homogenizing periodic media in the vicinity of ‘cell resonances’. The similarity of such model equations to high-frequency long wavelength asymptotics, for homogeneous acoustic and elastic waveguides, valid in the vicinities of thickness resonances is emphasized. Several illustrative examples are considered and show the efficacy of the developed techniques.NSERC (Canada) and the EPSRC

Flavaglines Alleviate Doxorubicin Cardiotoxicity: Implication of Hsp27

Background: Despite its effectiveness in the treatment of various cancers, the use of doxorubicin is limited by a potentially fatal cardiomyopathy. Prevention of this cardiotoxicity remains a critical issue in clinical oncology. We hypothesized that flavaglines, a family of natural compounds that display potent neuroprotective effects, may also alleviate doxorubicininduced cardiotoxicity. Methodology/Principal Findings: Our in vitro data established that a pretreatment with flavaglines significantly increased viability of doxorubicin-injured H9c2 cardiomyocytes as demonstrated by annexin V, TUNEL and active caspase-3 assays. We demonstrated also that phosphorylation of the small heat shock protein Hsp27 is involved in the mechanism by which flavaglines display their cardioprotective effect. Furthermore, knocking-down Hsp27 in H9c2 cardiomyocytes completely reversed this cardioprotection. Administration of our lead compound (FL3) to mice attenuated cardiomyocyte apoptosis and cardiac fibrosis, as reflected by a 50 % decrease of mortality. Conclusions/Significance: These results suggest a prophylactic potential of flavaglines to prevent doxorubicin-induce

Collagen scaffolds with tailored pore geometry for building three-dimensional vascular networks

Collagen scaffolds provide a promising platform for tissue regeneration due to their ability to support cell attachment, proliferation and differentiation. In this study, we used porous freeze-dried collagen scaffolds with either uniaxially-aligned or randomly-oriented pores to investigate the formation of vascular structures in vitro. We characterised the scaffold pore structure, specific permeability, cell migration and endothelial cell self-assembly into vessel-like networks in mono- and co-culture with osteoblasts. Our work shows that improved pre-vascularisation can be achieved in uniaxially-aligned scaffolds and in a co-culture environment

Collagen scaffolds with tailored pore geometry for building three-dimensional vascular networks

Collagen scaffolds provide a promising platform for tissue regeneration due to their ability to support cell attachment, proliferation and differentiation. In this study, we used porous freeze-dried collagen scaffolds with either uniaxially-aligned or randomly-oriented pores to investigate the formation of vascular structures in vitro. We characterised the scaffold pore structure, specific permeability, cell migration and endothelial cell self-assembly into vessel-like networks in mono- and co-culture with osteoblasts. Our work shows that improved pre-vascularisation can be achieved in uniaxially-aligned scaffolds and in a co-culture environment.Marie Skłodowska-Curie Fellowship Blavatnik Fellowship EPSRC (EP/R511675/1

Fabrication of PEGylated fibrinogen: A versatile injectable hydrogel biomaterial

Hydrogels are one of the most versatile biomaterials in use for tissue engineering and regenerative medicine. They are assembled from either natural or synthetic polymers, and their high water content gives these materials practical advantages in numerous biomedical applications. Semisynthetic hydrogels, such as those that combine synthetic and biological building blocks, have the added advantage of controlled bioactivity and material properties. In myocardial regeneration, injectable hydrogels premised on a semisynthetic design are advantageous both as bioactive bulking agents and as a delivery vehicle for controlled release of bioactive factors and/or cardiomyocytes. A new semisynthetic hydrogel based on PEGylated fibrinogen has been developed to address the many requirements of an injectable biomaterial in cardiac restoration. This chapter highlights the fundamental aspects of making this biomimetic hydrogel matrix for cardiac applications. © 2014 Springer Science+Business Media New York

Protein composition alters invivo resorption of PEG-based hydrogels as monitored by contrast-enhanced MRI

We report on the use of magnetic resonance imaging (MRI)-based non-invasive monitoring to document the role of protein adjuvants in hydrogel implant integration invivo. Polyethylene glycol (PEG) hydrogels were formed with different protein constituents, including albumin, fibrinogen and gelatin. The hydrogels were designed to exhibit similar material properties, including modulus, swelling and hydrolytic degradation kinetics. The invivo resorption properties of these PEG-based hydrogels, which contained a tethered gadolinium contrast agent, were characterized by MRI and histology, and compared to their invitro characteristics. MRI data revealed that PEG-Albumin implants remained completely intact throughout the experiments, PEG-Fibrinogen implants lost about 10% of their volume and PEG-Gelatin implants underwent prominent swelling and returned to their initial volume by day 25. Fully synthetic PEG-diacrylate (PEG-DA) control hydrogels lost about half of their volume after 25 days invivo. Transverse MRI cross-sections of the implants revealed distinct mechanisms of the hydrogel's biodegradation: PEG-Fibrinogen and PEG-Albumin underwent surface erosion, whereas PEG-Gelatin and PEG-DA hydrogels mainly underwent bulk degradation. Histological findings substantiated the MRI data and demonstrated significant cellular response towards PEG-DA and PEG-Gelatin scaffolds with relatively low reaction towards PEG-Fibrinogen and PEG-Albumin hydrogels. These findings demonstrate that PEG-protein hydrogels can degrade via a different mechanism than PEG hydrogels, and that this difference can be linked to a reduced foreign body response

Using bimodal MRI/fluorescence imaging to identify host angiogenic response to implants

Therapies that promote angiogenesis have been successfully applied using various combinations of proangiogenic factors together with a biodegradable delivery vehicle. In this study we used bimodal noninvasive monitoring to show that the host response to a proangiogenic biomaterial can be drastically affected by the mode of implantation and the surface area-to-volume ratio of the implant material. Fluorescence/MRI probes were covalently conjugated to VEGF-bearing biodegradable PEG-fibrinogen hydrogel implants and used to document the in vivo degradation and liberation of bioactive constituents in an s.c. rat implantation model. The hydrogel biodegradation and angiogenic host response with three types of VEGF-bearing implant configurations were compared: preformed cylindrical plugs, preformed injectable microbeads, and hydrogel precursor, injected and polymerized in situ. Although all three were made with identical amounts of precursor constituents, the MRI data revealed that in situ polymerized hydrogels were fully degraded within 2 wk; microbead degradation was more moderate, and plugs degraded significantly more slowly than the other configurations. The presence of hydrogel degradation products containing the fluorescent label in the surrounding tissues revealed a distinct biphasic release profile for each type of implant configuration. The purported in vivo VEGF release profile from the microbeads resulted in highly vascularized s.c. tissue containing up to 16-fold more capillaries in comparison with controls. These findings demonstrate that the configuration of an implant can play an important role not only in the degradation and resorption properties of the materials, but also in consequent host angiogenic response