Degradable poly(ethylene glycol)-based hydrogels:synthesis, physico-chemical properties and in vitro characterization

Designing degradable hydrogels is complicated by the structural and temporal complexities of the gel and evolving tissue. A major challenge is to create scaffolds with sufficient mechanical properties to restore initial function while simultaneously controlling temporal changes in the gel structure to facilitate tissue formation. Poly(ethylene glycol) was used in this work, to form biodegradable poly(ethylene glycol)-based hydrogels with hydrolyzable poly-l-lactide segments in the backbone. Non-degradable poly(ethylene glycol) was also introduced in the formulation to obtain control of the degradation profile that encompasses cell growth and new tissue formation. The dependence on polymer composition was observed by higher degradation profiles and decreased mechanical properties as the content of degradable segments was increased in the formulation. Based on in vitro tests, no toxicity of extracts or biomaterial in direct contact with human adipose tissue stem cells was observed, and the ultraviolet light treatment did not affect the proliferation capacity of the cells.

A novel and rational approach towards designing aluminium chelators

Aluminium (Al) is known to be neurotoxic and has been associated with the aetiology of Alzheimer's Disease. To date, only desferrioxamine (DFO), a trihydroxamic acid siderophore has been used in the clinical environment for the removal of Al from the body. However, this drug is expensive, orally inactive and is associated with many side effects. These studies employed a theoretical approach, with the use of quantum mechanics (QM) via semi-empirical molecular orbital (MO) calculations, and a practical approach using U87-MG glioblastoma cells as a model for evaluating the influence of potential chelators on the passage of aluminium into cells. Preliminary studies involving the Cambridge Structural Database (CSD) identified that Al prefers binding to bidentate ligands in a 3:1 manner, whereby oxygen was the exclusive donating atom. Statistically significant differences in M-O bond lengths when compared to other trivalent metal ions such as Fe3+ were established and used as an acceptance criterion for subsequent MO calculations. Of the semi-empirical methods parameterised for Al, the PM3 Hamiltonian was found to give the most reliable final optimised geometries of simple 3:1 Al complexes. Consequently the PM3 Hamiltonian was used for evaluating the Hf of 3:1 complexes with more complicated ligands. No correlation exists between published stability constants and individual parameters calculated via PM3 optimisations, although investigation of the dicarboxylates reveals a correlation of 0.961 showing promise for affinity prediction of closely related ligands. A simple and inexpensive morin spectrofluorescence assay has been developed and optimised producing results comparable to atomic absorption spectroscopy methods for the quantitative analysis of Al. This assay was used in subsequent in vitro models, initially on E. coli, which indicated that Al inhibits the antimicrobial action of ciprofloxacin, a potent quinolone antibiotic. Ensuing studies using the second model, U87-MG cells, investigated the influence of chelators on the transmembrane transport of Al, identifying 1,2-diethylhydroxypyridin-4-one as a ligand showing greatest potential for chelating Al in the clinical situation. In conclusion, these studies have explored semi-empirical MO Hamiltonians and an in-vitro U87-MG cell line, both as possible methods for predicting effective chelators of Al.

INTAMAP: the design and implementation of an interoperable automated interpolation web service

INTAMAP is a Web Processing Service for the automatic spatial interpolation of measured point data. Requirements were (i) using open standards for spatial data such as developed in the context of the Open Geospatial Consortium (OGC), (ii) using a suitable environment for statistical modelling and computation, and (iii) producing an integrated, open source solution. The system couples an open-source Web Processing Service (developed by 52°North), accepting data in the form of standardised XML documents (conforming to the OGC Observations and Measurements standard) with a computing back-end realised in the R statistical environment. The probability distribution of interpolation errors is encoded with UncertML, a markup language designed to encode uncertain data. Automatic interpolation needs to be useful for a wide range of applications and the algorithms have been designed to cope with anisotropy, extreme values, and data with known error distributions. Besides a fully automatic mode, the system can be used with different levels of user control over the interpolation process.

Modeling and validating dynamic adaptation

This paper discusses preliminary work on modeling and validation dynamic adaptation. The proposed approach is on the use of aspect-oriented modeling (AOM) and models at runtime. Our approach covers design and runtime phases. At design-time, a base model and different variant architecture models are designed and the adaptation model is built. Crucially, the adaptation model includes invariant properties and constraints that allow the validation of the adaptation rules before execution. During runtime, the adaptation model is processed to produce a correct system configuration that can be executed.

An aspect-oriented and model-driven approach for managing dynamic variability

Constructing and executing distributed systems that can adapt to their operating context in order to sustain provided services and the service qualities are complex tasks. Managing adaptation of multiple, interacting services is particularly difficult since these services tend to be distributed across the system, interdependent and sometimes tangled with other services. Furthermore, the exponential growth of the number of potential system configurations derived from the variabilities of each service need to be handled. Current practices of writing low-level reconfiguration scripts as part of the system code to handle run time adaptation are both error prone and time consuming and make adaptive systems difficult to validate and evolve. In this paper, we propose to combine model driven and aspect oriented techniques to better cope with the complexities of adaptive systems construction and execution, and to handle the problem of exponential growth of the number of possible configurations. Combining these techniques allows us to use high level domain abstractions, simplify the representation of variants and limit the problem pertaining to the combinatorial explosion of possible configurations. In our approach we also use models at runtime to generate the adaptation logic by comparing the current configuration of the system to a composed model representing the configuration we want to reach. © 2008 Springer-Verlag Berlin Heidelberg.

Summary of the 7th international workshop on Models@run.time

The Models@run.time (MRT) workshop series offers a discussion forum for the rising need to leverage modeling techniques for the software of the future. The main goals are to explore the benefits of models@run.time and to foster collaboration and cross-fertilization between different research communities like for example like model-driven engineering (e.g. MODELS), self-adaptive/autonomous systems communities (e.g., SEAMS and ICAC), the control theory community and the artificial intelligence community. © 2012 Authors.

Fabrication and characterization of macroporous poly(ethylene glycol) hydrogels generated by several types of porogens

Polymer scaffolds play an important role in tissue engineering applications. Poly(ethylene glycol) based hydrogels have received a lot of attention in this field because of their high biocompatibility and ease of processing. However, in many cases they do not exhibit proper tissue invasion and nutrient transport because of their dense structure. In the present work, several approaches were developed and compared to each other to produce interconnected macroporous poly(ethylene glycol) hydrogels by including different types of porogens in the photocrosslinking reaction. The swelling capacity of the resulting hydrogels was analyzed and compared to non-porous hydrogel samples. Moreover, the obtained materials were characterized by means of mechanical properties and porosity using rheometry, scanning electron microscopy, and mercury intrusion porosimetry. Results showed that interconnected and uniform pores were obtained when a porogen template was used during hydrogel fabrication by photocrosslinking. On the other side, when the porogen particles were dispersed into the macromer solution before matrix photocrosslinking the interconnexion was negligible. The templates must be dissolved before the hydrogel's cell-seeding in vitro, while the dispersed porogen can be used in situ in the in vitro seeding tests. Copyright © 2013 Taylor & Francis Group, LLC.

Multifunctional bioactive glass scaffolds coated with layers of poly(d,l-lactide-co-glycolide) and poly(n-isopropylacrylamide-co-acrylic acid) microgels loaded with vancomycin

A new family of multifunctional scaffolds, incorporating selected biopolymer coatings on basic Bioglass® derived foams has been developed. The polymer coatings were investigated as carrier of vancomycin which is a suitable drug to impart antibiotic function to the scaffolds. It has been proved that coating with PLGA (poly(lactic-co-glycolic acid)) with dispersed vancomycin-loaded microgels provides a rapid delivery of drug to give antibacterial effects at the wound site and a further sustained release to aid mid to long-term healing. Furthermore, the microgels also improved the bioactivity of the scaffolds by acting as nucleation sites for the formation of HA crystals in simulated body fluid. © 2013 Elsevier B.V. All rights reserved.

Comparative study of dexamethasone and vancomycin release behavior from stimuli-sensitive microgel aqueous dispersions

Stimuli-sensitive microgels of poly(N-isopropylacrylamide-co-acrylic acid) (designated as P(NIPAAm-co-AA)) were prepared through precipitation polymerization. Their capacity to load and release different drugs under different conditions, including physiological, in a controlled manner was analyzed. Two drugs were assayed and compared: dexamethasone and vancomycin. The prepared microgel particles show good thermosensitivity. In addition, the amount of cross-linker used in the preparation of the microgels does not greatly influence the drug-release capability of P(NIPAAm-co-AA)), but the amount of drug used to load the microgels did result in bigger amounts of drug released afterwards. These results imply potential application of prepared stimuli-sensitive microgel dispersions as drug-delivery systems and tissue engineering materials.

Dynamic variability in adaptive systems

One of the reasons for using variability in the software product line (SPL) approach (see Apel et al., 2006; Figueiredo et al., 2008; Kastner et al., 2007; Mezini & Ostermann, 2004) is to delay a design decision (Svahnberg et al., 2005). Instead of deciding on what system to develop in advance, with the SPL approach a set of components and a reference architecture are specified and implemented (during domain engineering, see Czarnecki & Eisenecker, 2000) out of which individual systems are composed at a later stage (during application engineering, see Czarnecki & Eisenecker, 2000). By postponing the design decisions in such a manner, it is possible to better fit the resultant system in its intended environment, for instance, to allow selection of the system interaction mode to be made after the customers have purchased particular hardware, such as a PDA vs. a laptop. Such variability is expressed through variation points which are locations in a software-based system where choices are available for defining a specific instance of a system (Svahnberg et al., 2005). Until recently it had sufficed to postpone committing to a specific system instance till before the system runtime. However, in the recent years the use and expectations of software systems in human society has undergone significant changes.Today's software systems need to be always available, highly interactive, and able to continuously adapt according to the varying environment conditions, user characteristics and characteristics of other systems that interact with them. Such systems, called adaptive systems, are expected to be long-lived and able to undertake adaptations with little or no human intervention (Cheng et al., 2009). Therefore, the variability now needs to be present also at system runtime, which leads to the emergence of a new type of system: adaptive systems with dynamic variability.