Durotactic control within a 3D collagen matrix

INTRODUCTION: While matrix stiffness has been implicated in cell adhesion and migration, most studies have focused on the effects of substrate stiffness in 2D. This work describes a novel continuous stiffness gradient model for studying such processes in 3D

Engineering physical structure in biomimetic collagen scaffolds: strategies for regulating cell behavior

Tissue engineering has traditionally relied on the use of scaffolds as inert, durable materials for seeded cells to re-grow. However, a paradigm shift in the role of scaffolds has become necessary towards bio-functional ‘devices’ which directly mimic native tissue matrix. It is key to control extracellular matrix remodelling and tissue structure by building control cues into the initial cell support matrix. The aim of this study was to test the effect and predictability of physical cues, engineered into 3D native collagen scaffolds by a cell-independent fabrication method, Plastic Compression (PC). Our findings indicated that fluid expulsion during collagen hydrogel compression produced anisotropic structuring and could be modelled as an ultrafiltration process. A groove/ridge topography engineered on collagen scaffolds through pattern-template-embossing influenced endothelial cell attachment/orientation and keratinocyte stratification in culture. Matrix collagen density and stiffness were directly related to its hydration level and could be controlled by limiting the extent of compression. Human-Dermal-Fibroblast (HDF) proliferation was proportional to matrix stiffness. In addition HDFs, seeded evenly within a PC collagen stiffness gradient, migrated and accumulated at the stiff end after 6 days. Bi-layer collagen matrices underwent cell-mediated integration, but despite higher cell migration across the interface in compliant than in stiff matrices at 24hrs, there was no significant difference in interface adhesive strength at 1 week. Core O2 tension in 3D spiral constructs directly correlated with total cell number along the diffusion path, i.e. consumption path length. This model was used to engineer local cell-mediated hypoxia in 3D constructs to generate populations of hypoxia-induced-signalling cells which produced angiogenic factor protein cascades. This in turn induced directed, functional micro-vascular ingrowth in vitro and in vivo. These data indicate how directing physical cues can be built into the structure of biomimetic, tissue-like scaffolds. This helps to understand intricate cell-matrix behaviours without reliance on complex biological control mechanisms and points the way to using simple physical cues for tissue formation

Engineering angiogenesis by hypoxia-induced signaling: Adopting a physiological approach

Successful engineering of tissues with clinically relevant size and complexity critically depends on their in vitro pre-vascularization which can promote cell survival, differentiation and rapid vascularization post-implantation. However, mimicking in vitro the physiological complexity of a vascular network currently presents major obstacles1. In this study we tested the hypothesis that a hypoxia-induced signaling (HIS) - cell population can generate the complete angiogenic cascade necessary for inducing endothelial cell sprouting and tubule formation within a 3D construct

Topographic patterning of 3D collagen scaffolds: From surface to interface engineering

Topographic patterning provides a useful tool for regulating cell function, such as adhesion, proliferation, differentiation and contact-guidance. While current (e.g.lithographic) techniques allow precise control of topographic pattern (anisotropic vs isotropic) and scale (nano- vs micro-topography) 1, they are only applicable to 2D surface patterning, which compromises their relevance to 3D tissue engineering. In this study we developed a novel method for rapid fabrication of micro-textured 3D collagen scaffolds

Endothelial cell migration and aggregation in response to hypoxia-induced signalling

The vascularisation of any graft, engineered implant or injury site is a key factor for optimal repair and regeneration. New blood vessel formation is a physiological response to tissue hypoxia, through upregulation of angiogenic factor signalling. We engineered cell-mediated hypoxia in a convenient cell type, human dermal fibroblasts (HDFs), to form a population of Hypoxia-Induced Signalling (HIS) cells and showed that HIS responses by HDFs induce endothelial cell (EC) migration and tubule formation both in vitro and in viv

Longitudinal photocurrent spectroscopy of a single GaAs/AlGaAs v-groove quantum wire

Modulation-doped GaAs v-groove quantum wires (QWRs) have been fabricated with novel electrical contacts made to two-dimensional electron-gas (2DEG) reservoirs. Here, we present longitudinal photocurrent (photoconductivity/PC) spectroscopy measurements of a single QWR. We clearly observe conductance in the ground-state one-dimensional subbands; in addition, a highly temperature-dependent response is seen from other structures within the v-groove. The latter phenomenon is attributed to the effects of structural topography and localization on carrier relaxation. The results of power-dependent PC measurements suggest that the QWR behaves as a series of weakly interacting localized states, at low temperatures

Multicohort cross-sectional study of cognitive and behavioural digital biomarkers in neurodegeneration: the Living Lab Study protocol

INTRODUCTION AND AIMS: Digital biomarkers can provide a cost-effective, objective and robust measure for neurological disease progression, changes in care needs and the effect of interventions. Motor function, physiology and behaviour can provide informative measures of neurological conditions and neurodegenerative decline. New digital technologies present an opportunity to provide remote, high-frequency monitoring of patients from within their homes. The purpose of the living lab study is to develop novel digital biomarkers of functional impairment in those living with neurodegenerative disease (NDD) and neurological conditions. METHODS AND ANALYSIS: The Living Lab study is a cross-sectional observational study of cognition and behaviour in people living with NDDs and other, non-degenerative neurological conditions. Patients (n≥25 for each patient group) with dementia, Parkinson's disease, amyotrophic lateral sclerosis, mild cognitive impairment, traumatic brain injury and stroke along with controls (n≥60) will be pragmatically recruited. Patients will carry out activities of daily living and functional assessments within the Living Lab. The Living Lab is an apartment-laboratory containing a functional kitchen, bathroom, bed and living area to provide a controlled environment to develop novel digital biomarkers. The Living Lab provides an important intermediary stage between the conventional laboratory and the home. Multiple passive environmental sensors, internet-enabled medical devices, wearables and electroencephalography (EEG) will be used to characterise functional impairments of NDDs and non-NDD conditions. We will also relate these digital technology measures to clinical and cognitive outcomes. ETHICS AND DISSEMINATION: Ethical approvals have been granted by the Imperial College Research Ethics Committee (reference number: 21IC6992). Results from the study will be disseminated at conferences and within peer-reviewed journals

The Social, Educational and Market Scenario for nZEB in Europe

Nearly Zero Energy Buildings (nZEB) are a significant part of the energy efficiency strategy of the European Union. As buildings represent approximately 40% of the final energy use in Europe, the reduction of their energy demand is key for a sustainable future. This paper takes a qualitative approach and presents data about professional and market barriers, as well as the educational market in relation to the implementation of nZEB policies for new and retrofit buildings in 11 European countries. Different levels of policy enactments and market penetration are reported and are generally found to be more advanced in western and central European countries. Furthermore, gender equality is examined in the building sector in relation to nZEB and presents significant gaps, with a more balanced situation reported in southern Europe. The accreditation and targeted education of nZEB experts is still almost non-existent in the examined countries, and the need for training of building professionals is highlighted as a critical missing component of current policy. This research aims to be the first step towards the creation of educational material and programmes as a mean to accelerate the transition to nZEB.European Union’s Horizon 2020 research and innovation programm

In vitro studies and preliminary in vivo evaluation of silicified concentrated collagen hydrogels

Hybrid and nanocomposite silicacollagen materials derived from concentrated collagen hydrogels were evaluated in vitro and in vivo to establish their potentialities for biological dressings. Silicification significantly improved the mechanical and thermal stability of the collagen network within the hybrid systems. Nanocomposites were found to favor the metabolic activity of immobilized human dermal fibroblastswhile decreasing the hydrogel contraction. Cell adhesion experiments suggested that in vitro cell behavior was dictated by mechanical properties and surface structure of the scaffold. First-to-date in vivo implantation of bulk hydrogels in subcutaneous sites of rats was performed over the vascular inflammatory period. These materials were colonized and vascularized without inducing strong inflammatory response. These data raise reasonable hope for the future application of silicacollagen biomaterials as biological dressings.Fil: Desimone, Martín Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; ArgentinaFil: Hélary, Christophe. Université Pierre et Marie Curie; FranciaFil: Quignard, Sandrine. Université Pierre et Marie Curie; FranciaFil: Rietveld, Ivo B. Universite de Paris; FranciaFil: Bataille, Clement. Université de Versailles Saint-quentin-en-yvelines.; FranciaFil: Copello, Guillermo Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; ArgentinaFil: Mosser, Gervaise. Université Pierre et Marie Curie; FranciaFil: Giraud Guille, Marie-Madeleine. Université Pierre et Marie Curie; FranciaFil: Livage, Jacques. Université Pierre et Marie Curie; FranciaFil: Meddahi Pellé, Anne. Université de Versailles Saint-quentin-en-yvelines.; FranciaFil: Coradin, Thibaud. Université Pierre et Marie Curie; Franci