Advanced hydrogels based on natural macromolecules: chemical routes to achieve mechanical versatility

Advances in synthetic routes to chemically modify natural macromolecules such as polysaccharides and proteins have allowed designing functional hydrogels able to tackle current challenges in the biomedical field. Hydrogels are hydrophilic three-dimensional systems able to absorb or retain a large volume of water, prepared from a low percentage of precursor macromolecules. The typical fragile elastic structure of common hydrogel formulations often limits their usage. Three main fabrication strategies involving several compounds or multimodified materials known as double networks, dual-crosslinked networks, and interpenetrating networks have been explored to impart mechanical strength to hydrogels. Widely investigated for synthetic polymers, these approaches allow obtaining added-value hydrogels with a large spectrum of mechanical properties. Advances in the development of such hydrogels with biomacromolecules as main constituent materials have enabled the fabrication of hydrogels with improved key properties for medical use, including biocompatibility, controlled release of active substances and tailored biodegradability, while exploring sustainable sources. This review describes recent advances in the use of proteins, as well as natural and semi-synthetic polymers for the fabrication of hydrogels for biomedical applications. Structures processed via double network, dual-crosslinked, or interpenetrating network strategies are reviewed, and emphasis is given to the type of chemical modifications and reactions, as well as the covalent and non-covalent interactions/bonds involved in those mechanisms.publishe

Investigating the Vascularization of Tissue-Engineered Bone Constructs Using Dental Pulp Cells and 45S5 Bioglass(®) Scaffolds.

Identification of a suitable cell source combined with an appropriate 3D scaffold is an essential prerequisite for successful engineering of skeletal tissues. Both osteogenesis and angiogenesis are key processes for bone regeneration. This study investigated the vascularization potential of a novel combination of human dental pulp stromal cells (HDPSCs) with 45S5 Bioglass(®) scaffolds for tissue-engineered mineral constructs in vivo and in vitro. 45S5 Bioglass scaffolds were produced by the foam replication technique with the standard composition of 45 wt% SiO2, 24.5 wt% Na2O, 24.5 wt% CaO, and 6 wt% P2O5. HDPSCs were cultured in monolayers and on porous 45S5 Bioglass scaffolds under angiogenic and osteogenic conditions for 2-4 weeks. HDPSCs expressed endothelial gene markers (CD34, CD31/PECAM1, and VEGFR2) under both conditions in the monolayer. A combination of HDPSCs with 45S5 Bioglass enhanced the expression of these gene markers. Positive immunostaining for CD31/PECAM1 and VEGFR2 and negative staining for CD34 supported the gene expression data, while histology revealed evidence of endothelial cell-like morphology within the constructs. More organized tubular structures, resembling microvessels, were seen in the constructs after 8 weeks of implantation in vivo. In conclusion, this study suggests that the combination of HDPSCs with 45S5 Bioglass scaffolds offers a promising strategy for regenerating vascularized bone grafts

Mechanical properties of highly porous PDLLA/Bioglass (R) composite foams as scaffolds for bone tissue engineering

This study developed highly porous degradable composites as potential scaffolds for bone tissue engineering. These scaffolds consisted of poly-d,l-lactic acid filled with 2 and 15 vol.% of 45S5 Bioglass® particles and were produced via thermally induced solid–liquid phase separation and subsequent solvent sublimation. The scaffolds had a bimodal and anisotropic pore structure, with tubular macro-pores of 100 μm in diameter, and with interconnected micro-pores of 10–50 μm in diameter. Quasi-static and thermal dynamic mechanical analysis carried out in compression along with thermogravimetric analysis was used to investigate the effect of Bioglass® on the properties of the foams. Quasi-static compression testing demonstrated mechanical anisotropy concomitant with the direction of the macro-pores. An analytical modelling approach was applied, which demonstrated that the presence of Bioglass® did not significantly alter the porous architecture of these foams and reflected the mechanical anisotropy which was congruent with the scanning electron microscopy investigation. This study found that the Ishai–Cohen and Gibson–Ashby models can be combined to predict the compressive modulus of the composite foams. The modulus and density of these complex foams are related by a power-law function with an exponent between 2 and 3

Historical analogues of the recent extreme minima observed in the Atlantic meridional overturning circulation at 26°N

Observations of the Atlantic meridional overturning circulation (AMOC) by the RAPID 26°N array show a pronounced minimum in the northward transport over the winter of 2009/10, substantially lower than any observed since the initial deployment in April 2004. It was followed by a second minimum in the winter of 2010/2011. We demonstrate that ocean models forced with observed surface fluxes reproduce the observed minima. Examining output from five ocean model simulations we identify several historical events which exhibit similar characteristics to those observed in the winter of 2009/10, including instances of individual events, and two clear examples of pairs of events which happened in consecutive years, one in 1969/70 and another in 1978/79. In all cases the absolute minimum, associated with a short, sharp reduction in the Ekman component, occurs in winter. AMOC anomalies are coherent between the Equator and 50°N and in some cases propagation attributable to the poleward movement of the anomaly in the wind field is observed. We also observe a low frequency (decadal) mode of variability in the anomalies, associated with the North Atlantic Oscillation (NAO). Where pairs of events have occurred in consecutive years we find that atmospheric conditions during the first winter correspond to a strongly negative Arctic Oscillation (AO) index. Atmospheric conditions during the second winter are indicative of a more regional negative NAO phase, and we suggest that this persistence is linked to re-emergence of sea surface temperature anomalies in the North Atlantic for the events of 1969/70 and 2009/10. The events of 1978/79 do not exhibit re-emergence, indicating that the atmospheric memory for this pair of events originates elsewhere. Observation of AO patterns associated with cold winters over northwest Europe may be indicative for the occurrence of a second extreme winter over northwest Europe

Chaotic variability of the meridional overturning circulation on subannual to interannual timescales

Observations and numerical simulations have shown that the meridional overturning circulation (MOC) exhibits substantial variability on sub- to interannual timescales. This variability is not fully understood. In particular it is not known what fraction of the MOC variability is caused by processes such as mesoscale ocean eddies and waves which are ubiquitous in the ocean. Here we analyse twin experiments performed with a global ocean model at eddying (1/4°) and non-eddying (1°) resolutions. The twin experiments are forced with the same surface fluxes for the 1958 to 2001 period but start from different initial conditions. Our results show that on subannual to interannual timescales a large fraction of MOC variability directly reflects variability in the surface forcing. Nevertheless, in the eddy-permitting case there is an initial-condition-dependent MOC variability (hereinafter referred to as "chaotic" variability) of several Sv (1Sv = 106 m3 s?1) in the Atlantic and the Indo-Pacific. In the Atlantic the chaotic MOC variability represents up to 30% of the total variability at the depths where the maximum MOC occurs. In comparison the chaotic MOC variability is only 5–10% in the non-eddying case. The surface forcing being almost identical in the twin experiments suggests that mesoscale ocean eddies are the most likely cause for the increased chaotic MOC variability in the eddying case. The exact formation time of eddies is determined by the initial conditions which are different in the two model passes, and as a consequence the mesoscale eddy field is decorrelated in the twin experiments. In regions where eddy activity is high in the eddy-permitting model, the correlation of sea surface height variability in the twin runs is close to zero. In the non-eddying case in contrast, we find high correlations (0.9 or higher) over most regions. Looking at the sub- and interannual MOC components separately reveals that most of the chaotic MOC variability is found on subannual timescales for the eddy-permitting model. On interannual timescales the amplitude of the chaotic MOC variability is much smaller and the amplitudes are comparable for both the eddy-permitting and non-eddy-permitting model resolutions. Whereas the chaotic MOC variability on interannual timescales only accounts for a small fraction of the total chaotic MOC variability in the eddy-permitting case, it is the main contributor to the chaotic variability in the non-eddying case away from the Equator

Preparation and characterisation of poly(lactide-co-glycolide) (PLGA) and PLGA/Bioglass((R)) composite tubular foam scaffolds for tissue engineering applications

Polylactide-co-glycolide (PLGA) and PLGA/Bioglass(R) foams of tubular shape have been prepared with a 1 wt% 45S5 Bioglass(R) content. Porous membranes with varying thickness and porosity were fabricated via a thermally induced phase separation process from which tubes of controlled diameter and wall thickness in the range 1.5-3 mm were produced. Scanning electron microscopy (SEM) revealed that the structure of the tubular foams consisted of radially oriented and highly interconnected pores with two distinct pore sizes, i.e. macropores similar to100-mum average diameter and interconnected micropores of 10-50-mum diameter. Foams with Bioglass(R) inclusions showed similarly well-defined tubular and interconnected pore morphology. Cell culture studies using mouse fibroblasts (L929) were conducted to assess the biocompatibility of the scaffolds in vitro. L929 fibroblasts cultured in medium that was pre-conditioned by incubating with PLGA tubes containing Bioglass(R) had a significant reduction in cell proliferation compared with fibroblasts grown in unconditioned medium (P < 0.0001). The PLGA and PLGA/Bioglass(R) tubular foams developed here are candidate materials for soft-tissue engineering scaffolds. holding promise for the regeneration of tissues requiring a tubular shape scaffold. such as intestine. trachea and blood vessels