ECM-enriched alginate hydrogels for bioartificial pancreas: an ideal niche to improve insulin secretion and diabetic glucose profile

Introduction: The success of a bioartificial pancreas crucially depends on ameliorating encapsulated beta cells survival and function. By mimicking the cellular in vivo niche, the aim of this study was to develop a novel model for beta cells encapsulation capable of establishing an appropriate microenvironment that supports interactions between cells and extracellular matrix (ECM) components. Methods: ECM components (Arg-Gly-Asp, abbreviated as RGD) were chemically incorporated in alginate hydrogels (alginate-RGD). After encapsulation, INS-1E beta cells outcome was analyzed in vitro and after their implantation in an animal model of diabetes. Results: Our alginate-RGD model demonstrated to be a good in vitro niche for supporting beta cells viability, proliferation, and activity, namely by improving the key feature of insulin secretion. RGD peptides promoted cell–matrix interactions, enhanced endogenous ECM components expression, and favored the assembly of individual cells into multicellular spheroids, an essential configuration for proper beta cell functioning. In vivo, our pivotal model for diabetes treatment exhibited an improved glycemic profile of type 2 diabetic rats, where insulin secreted from encapsulated cells was more efficiently used. Conclusions: We were able to successfully introduce a novel valuable function in an old ally in biomedical applications, the alginate. The proposed alginate-RGD model stands out as a promising approach to improve beta cells survival and function, increasing the success of this therapeutic strategy, which might greatly improve the quality of life of an increasing number of diabetic patients worldwide.The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by FCT/MEC through National Funds and co-financed by FEDER through the PT2020 Partnership Agreement under the 4293 Unit I&D, FCT Strategic Project PEst-C/SAU/UI3282/2011-2013 and UID/NEU/04539/2013, FCT in the framework of project UID/BIM/04293/2013, FCT in the framework of project IF/00939/2013/CP1179/CT0001, FCT for Joana Crisóstomo (grant number SFRH/BD/72964/2010), FCT for Sílvia J Bidarra (grant number SFRH/BPD/80571/2011), and FCT and POPH/ESF (EC) for Cristina C Barrias research position FCT Investigator (IF2013)

Structured Multi-Level Feature Interaction Identification

This is a conference paper.Features are an established means of adding non-geometric information and extra geometric semantics to conventional CAD systems. It has been already realised that although feature-based modelling is necessary for the next generation of integrated design and manufacturing systems, inherent feature interactions pose a difficulty in representing and manipulating geometric design. This paper presents a structured multi-level geometric feature interaction classification scheme implemented within a Design-by Feature (DbF) system for representation validation analysis. Various feature interaction definitions and classification methods are first surveyed. The elements and the tests used for the identification process are presented. The classification encompasses existing feature interference cases found in the literature, uses a clear structure for the classification and, is applied at three different levels

Mixed-media game AI

Over the last decades, digital technologies have moved away from the personal computer (PC) into cloud computing, ubiquitous computing, intelligent robots and smart devices. From wearable technologies to remote-controlled household items and from sensors for crowd control to personal drones, there is a broad range of sources which can be exploited for artificial intelligence in games. While artificial intelligence (AI) is already a big part of the Internet of Things, raising concerns in terms of ethics and politics, games have been relatively partitioned away to PCs. Relevant work on wearable technologies as game controllers, mixed- or virtual-reality rendering, or technology-enhanced play in playgrounds, social robots for games or board games, has largely not taken advantage of artificial intelligence for controlling or mediating the experience. Using the term mixed-media to refer broadly to any media, digital or otherwise, outside the game data within a PC or a game-specific database, this working group attempted to map out the broad topic of mixed-media in terms of its applications for game AI.peer-reviewe

Gelatin microparticles aggregates as three-dimensional scaffolding system in cartilage engineering

A three-dimensional (3D) scaffolding system for chondrocytes culture has been produced by agglomeration of cells and gelatin microparticles with a mild centrifuging process. The diameter of the microparticles, around 10 μ, was selected to be in the order of magnitude of the chondrocytes. No gel was used to stabilize the construct that maintained consistency just because of cell and extracellular matrix (ECM) adhesion to the substrate. In one series of samples the microparticles were charged with transforming growth factor, TGF-β1. The kinetics of growth factor delivery was assessed. The initial delivery was approximately 48 % of the total amount delivered up to day 14. Chondrocytes that had been previously expanded in monolayer culture, and thus dedifferentiated, adopted in this 3D environment a round morphology, both with presence or absence of growth factor delivery, with production of ECM that intermingles with gelatin particles. The pellet was stable from the first day of culture. Cell viability was assessed by MTS assay, showing higher absorption values in the cell/unloaded gelatin microparticle pellets than in cell pellets up to day 7. Nevertheless the absorption drops in the following culture times. On the contrary the cell viability of cell/TGF-β1 loaded gelatin microparticle pellets was constant during the 21 days of culture. The formation of actin stress fibres in the cytoskeleton and type I collagen expression was significantly reduced in both cell/gelatin microparticle pellets (with and without TGF-β1) with respect to cell pellet controls. Total type II collagen and sulphated glycosaminoglycans quantification show an enhancement of the production of ECM when TGF-β1 is delivered, as expected because this growth factor stimulate the chondrocyte proliferation and improve the functionality of the tissue.JLGR acknowledge the support of the Spanish Ministry of Education through project No. MAT2010-21611-C03-01 (including the FEDER financial support). The support of the Instituto de Salud Carlos III (ISCIII) through the CIBER initiative of the Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN) is also acknowledged

Oral manifestations of systemic disease

While the majority of disorders of the mouth are centred upon the direct action of plaque, the oral tissues can be subject to change or damage as a consequence of disease that predominantly affects other body systems. Such oral manifestations of systemic disease can be highly variable in both frequency and presentation. As lifespan increases and medical care becomes ever more complex and effective it is likely that the numbers of individuals with oral manifestations of systemic disease will continue to rise. The present article provides a succinct review of oral manifestations of systemic disease. In view of this article being part of a wider BDJ themed issue on the subject of oral medicine, this review focuses upon oral mucosal and salivary gland disorders that may arise as a consequence of systemic disease