Physics-informed deep generative learning for quantitative assessment of the retina.

Disruption of retinal vasculature is linked to various diseases, including diabetic retinopathy and macular degeneration, leading to vision loss. We present here a novel algorithmic approach that generates highly realistic digital models of human retinal blood vessels, based on established biophysical principles, including fully-connected arterial and venous trees with a single inlet and outlet. This approach, using physics-informed generative adversarial networks (PI-GAN), enables the segmentation and reconstruction of blood vessel networks with no human input and which out-performs human labelling.

Interplay of Physical, Psychological, and Social Frailty among Community-Dwelling Older Adults in Five European Countries: A Longitudinal Study.

Frailty is a dynamic condition encompassing physical, psychological, and social domains. While certain factors are associated with overall or specific frailty domains, research on the correlations between physical, psychological, and social frailty is lacking. This study aims to investigate the associations between physical, psychological, and social frailty in European older adults.

Densified collagen tubular grafts for human tissue replacement and disease modelling applications.

There is a significant need across multiple indications for an off-the-shelf bioengineered tubular graft which fulfils the mechanical and biological requirements for implantation and function but does not necessarily require cells for manufacture or deployment. Herein, we present a tissue-like tubular construct using a cell-free, materials-based method of manufacture, utilizing densified collagen hydrogel. Our tubular grafts are seamless, mechanically strong, customizable in terms of lumen diameter and wall thickness, and display a uniform fibril density across the wall thickness and along the tube length.

A vascularized tumoroid model for human glioblastoma angiogenesis.

Glioblastoma (GBM) angiogenesis is critical for tumor growth and recurrence, making it a compelling therapeutic target. Here, a disease-relevant, vascularized tumoroid in vitro model with stem-like features and stromal surrounds is reported. The model is used to recapitulate how individual components of the GBM's complex brain microenvironment such as hypoxia, vasculature-related stromal cells and growth factors support GBM angiogenesis.

Socio-demographic characteristics associated with emotional and social loneliness among older adults.

Background: International studies provide an overview of socio-demographic characteristics associated with loneliness among older adults, but few studies distinguished between emotional and social loneliness. This study examined socio-demographic characteristics associated with emotional and social loneliness.

Methods: Data of 2251 community-dwelling older adults, included at the baseline measure of the Urban Health Centers Europe (UHCE) project, were analysed.

Spatial heterogeneity of cell-matrix adhesive forces predicts human glioblastoma migration.

Background: Glioblastoma (GBM) is a highly aggressive incurable brain tumor. The main cause of mortality in GBM patients is the invasive rim of cells migrating away from the main tumor mass and invading healthy parts of the brain. Although the motion is driven by forces, our current understanding of the physical factors involved in glioma infiltration remains limited.

Functionalisation of a heat-derived and bio-inert albumin hydrogel with extracellular matrix by air plasma treatment.

Albumin-based hydrogels are increasingly attractive in tissue engineering because they provide a xeno-free, biocompatible and potentially patient-specific platform for tissue engineering and drug delivery. The majority of research on albumin hydrogels has focused on bovine serum albumin (BSA), leaving human serum albumin (HSA) comparatively understudied. Different gelation methods are usually employed for HSA and BSA, and variations in the amino acid sequences of HSA and BSA exist; these account for differences in the hydrogel properties.

Reliability and Validity of the Tilburg Frailty Indicator in 5 European Countries.

Objectives: To assess the internal consistency, convergent and divergent validity, and concurrent validity of the Tilburg Frailty Indicator (TFI) within community-dwelling older people in Spain, Greece, Croatia, the Netherlands, and the United Kingdom.

Design: Cross-sectional study.

Setting: Primary care and community settings.

Feasibility of Using 3D Printed Polyvinyl Alcohol (PVA) for Creating Self-Healing Vascular Tunnels in Cement System.

Pursuing long-term self-healing infrastructures has gained popularity in the construction field. Vascular networks have the potential to achieve long-term self-healing in cementitious infrastructures. To avoid further monitoring of non-cementitious tubes, sacrificial material can be used as a way of creating hollow channels.

Albumin-Enriched Fibrin Hydrogel Embedded in Active Ferromagnetic Networks Improves Osteoblast Differentiation and Vascular Self-Organisation.

Porous coatings on prosthetic implants encourage implant fixation. Enhanced fixation may be achieved using a magneto-active porous coating that can deform elastically in vivo on the application of an external magnetic field, straining in-growing bone. Such a coating, made of 444 ferritic stainless steel fibres, was previously characterised in terms of its mechanical and cellular responses.

Stimulation of Human Osteoblast Differentiation in Magneto-Mechanically Actuated Ferromagnetic Fiber Networks.

There is currently an interest in "active" implantable biomedical devices that include mechanical stimulation as an integral part of their design. This paper reports the experimental use of a porous scaffold made of interconnected networks of slender ferromagnetic fibers that can be actuated in vivo by an external magnetic field applying strains to in-growing cells. Such scaffolds have been previously characterized in terms of their mechanical and cellular responses.

3D Printable Vascular Networks Generated by Accelerated Constrained Constructive Optimization for Tissue Engineering.

One of the greatest challenges in fabricating artificial tissues and organs is the incorporation of vascular networks to support the biological requirements of the embedded cells, encouraging tissue formation and maturation. With the advent of 3D printing technology, significant progress has been made with respect to generating vascularized artificial tissues. Current algorithms to generate arterial/venous trees are computationally expensive and offer limited freedom to optimize the resulting structures.

Albumin-based hydrogels for regenerative engineering and cell transplantation.

Albumin, the most abundant plasma protein in mammals, is a versatile and easily obtainable biomaterial. It is pH and temperature responsive, dissolvable in high concentrations and gels readily in defined conditions. This versatility, together with its inexpensiveness and biocompatibility, makes albumin an attractive biomaterial for biomedical research and therapeutics.

A coordinated preventive care approach for healthy ageing in five European cities: A mixed methods study of process evaluation components.

Aims: To evaluate specific process components of the Urban Health Centres Europe (UHCE) approach; a coordinated preventive care approach aimed at healthy ageing by decreasing falls, polypharmacy, loneliness and frailty among older persons in community settings of five cities in the United Kingdom, Greece, Croatia, the Netherlands and Spain.

Design: Mixed methods evaluation of specific process components of the UHCE approach: reach of the target population, dose of the intervention actually delivered and received by participants and satisfaction and experience of main stakeholders involved in the approach.

Methods: The UHCE approach intervention consisted of a preventive assessment, shared decision-making on a care plan and enrolment in one or more of four coordinated care-pathways that targeted falls, polypharmacy, loneliness and frailty.

Association between physical, psychological and social frailty and health-related quality of life among older people.

Background: Studies on the association between frailty and health-related quality of life (HRQoL) are scarce and show contradictory results. This study aimed to evaluate the association between physical, psychological and social frailty and HRQoL among community-dwelling older people.

Methods: A cross-sectional study was performed with baseline data collected in 2015 from the Urban Health Centers Europe (UHCE) project in five European countries, the United Kingdom, Greece, Croatia, The Netherlands and Spain.

Isolation and propagation of primary human cholangiocyte organoids for the generation of bioengineered biliary tissue.

Pediatric liver transplantation is often required as a consequence of biliary disorders because of the lack of alternative treatments for repairing or replacing damaged bile ducts. To address the lack of availability of pediatric livers suitable for transplantation, we developed a protocol for generating bioengineered biliary tissue suitable for biliary reconstruction. Our platform allows the derivation of cholangiocyte organoids (COs) expressing key biliary markers and retaining functions of primary extra- or intrahepatic duct cholangiocytes within 2 weeks of isolation.

The effectiveness of a coordinated preventive care approach for healthy ageing (UHCE) among older persons in five European cities: A pre-post controlled trial.

Background: Older persons often have multiple health and social problems and need a variety of health services. A coordinated preventive approach that integrates the provision of health and social care services could promote healthy ageing. Such an approach can be organised differently, depending on the availability and organizational structures in the local context.

Advances in the generation of bioengineered bile ducts.

The generation of bioengineered biliary tissue could contribute to the management of some of the most impactful cholangiopathies associated with liver transplantation, such as biliary atresia or ischemic cholangiopathy. Recent advances in tissue engineering and in vitro cholangiocyte culture have made the achievement of this goal possible. Here we provide an overview of these developments and review the progress towards the generation and transplantation of bioengineered bile ducts.

Reconstruction of the mouse extrahepatic biliary tree using primary human extrahepatic cholangiocyte organoids.

The treatment of common bile duct (CBD) disorders, such as biliary atresia or ischemic strictures, is restricted by the lack of biliary tissue from healthy donors suitable for surgical reconstruction. Here we report a new method for the isolation and propagation of human cholangiocytes from the extrahepatic biliary tree in the form of extrahepatic cholangiocyte organoids (ECOs) for regenerative medicine applications. The resulting ECOs closely resemble primary cholangiocytes in terms of their transcriptomic profile and functional properties.

Effect of Rotation on Scaffold Motion and Cell Growth in Rotating Bioreactors.

Efficient use of different bioreactor designs to improve cell growth in three-dimensional scaffolds requires an understanding of their mechanism of action. To address this for rotating wall vessel bioreactors, fluid and scaffold motion were investigated experimentally at different rotation speeds and vessel fill volumes. Low cost bioreactors with single and dual axis rotation were developed to investigate the effect of these systems on human osteoblast proliferation in free floating and constrained collagen-glycosaminoglycan porous scaffolds.

Multi-casting approach for vascular networks in cellularized hydrogels.

Vascularization is essential for living tissue and remains a major challenge in the field of tissue engineering. A lack of a perfusable channel network within a large and densely populated tissue engineered construct leads to necrotic core formation, preventing fabrication of functional tissues and organs. We report a new method for producing a hierarchical, three-dimensional (3D) and perfusable vasculature in a large, cellularized fibrin hydrogel.

The influence of nanostructured features on bacterial adhesion and bone cell functions on severely shot peened 316L stainless steel.

Substrate grain structure and topography play major roles in mediating cell and bacteria activities. Severe plastic deformation techniques, known as efficient metal-forming and grain refining processes, provide the treated material with novel mechanical properties and can be adopted to modify nanoscale surface characteristics, possibly affecting interactions with the biological environment. This in vitro study evaluates the capability of severe shot peening, based on severe plastic deformation, to modulate the interactions of nanocrystallized metallic biomaterials with cells and bacteria.

Effect of microgrooved surface topography on osteoblast maturation and protein adsorption.

Microgrooved surfaces have been used extensively to influence cell contact guidance. Guiding cell growth, extracellular matrix deposition, and mineralization is important for bone implant longevity. In this study, we investigated the osteoblast response to microgrooved metallic surfaces in serum-supplemented medium.

Physical and biological characterization of ferromagnetic fiber networks: effect of fibrin deposition on short-term in vitro responses of human osteoblasts.

Ferromagnetic fiber networks have the potential to deform in vivo imparting therapeutic levels of strain on in-growing periprosthetic bone tissue. 444 Ferritic stainless steel provides a suitable material for this application due to its ability to support cultures of human osteoblasts (HObs) without eliciting undue inflammatory responses from monocytes in vitro. In the present article, a 444 fiber network, containing 17 vol% fibers, has been investigated.

Short-term in vitro responses of human peripheral blood monocytes to ferritic stainless steel fiber networks.

Beneficial effects on bone-implant bonding may accrue from ferromagnetic fiber networks on implants which can deform in vivo inducing controlled levels of mechanical strain directly in growing bone. This approach requires ferromagnetic fibers that can be implanted in vivo without stimulating undue inflammatory cell responses or cytotoxicity. This study examines the short-term in vitro responses, including attachment, viability, and inflammatory stimulation, of human peripheral blood monocytes to 444 ferritic stainless steel fiber networks.