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Implantable hydrogels should ideally possess mechanical properties matched to the surrounding tissues to enable adequate mechanical function while regeneration occurs. This can be challenging, especially when degradable systems with high water content and hydrolysable chemical bonds are required in anatomical sites under constant mechanical stimulation, e.g. a foot ulcer cavity. In these circumstances, the design of hydrogel composites is a promising strategy to provide controlled structural features and macroscopic properties over time. To explore this strategy, the synthesis of a new photocurable elastomeric polymer, poly(glycerol-co-sebacic acid-co-lactic acid-co-polyethylene glycol) acrylate (PGSLPA), is investigated, along with its processing into UV-cured hydrogels, electrospun nonwovens and fibre-reinforced variants, without the need for a high temperature curing step or use of hazardous solvents. The mechanical properties of bioresorbable PGSLPA hydrogels were studied with and without electrospun nonwoven reinforcement and with varied layered configurations, aiming to determine the effects of microstructure on bulk compressive strength and elasticity. The nonwoven reinforced PGSLPA hydrogels exhibited a 60 % increase in compressive strength and an 80 % increase in elastic moduli compared to fibre-free PGSLPA samples. Mechanical properties of the fibre-reinforced hydrogels could also be modulated by altering the layering arrangement of the nonwoven and hydrogel phase. The nanofibre reinforced PGSLPA hydrogels also exhibited good elastic recovery, as evidenced by hysteresis in compression fatigue stress-strain evaluations showing a return to original dimensions., Comment: 26 pages, 12 figures, 3 tables. Accepted in Polymers

The fast degradation of collagen-based membranes in the biological environment remains a critical challenge, resulting in underperforming Guided Bone Regeneration (GBR) therapy leading to compromised clinical results. Photoactive atelocollagen (AC) systems functionalised with ethylenically unsaturated monomers, such as 4-vinylbenzyl chloride (4VBC), have been shown to generate mechanically competent materials for wound healing, inflammation control and drug delivery, whereby control of the molecular architecture of the AC network is key. Building on this platform, the sequential functionalisation with 4VBC and methacrylic anhydride (MA) was hypothesised to generate UV-cured AC hydrogels with reduced swelling ratio, increased proteolytic stability and barrier functionality for GBR therapy. The sequentially functionalised atelocollagen precursor (SAP) was characterised via TNBS and ninhydrin colourimetric assays, circular dichroism and UV-curing rheometry, which confirmed nearly complete consumption of collagen primary amino groups, preserved triple helices and fast (within 180 s) gelation kinetics, respectively. Hydrogel swelling ratio and compression modulus were adjusted depending on the aqueous environment used for UV-curing, whilst the sequential functionalisation of AC successfully generated hydrogels with superior proteolytic stability in vitro compared to both 4VBC functionalised control and the commercial dental membrane Bio-Gide. These in vitro results were confirmed in vivo via both subcutaneous implantation and a proof-of-concept study in a GBR calvarial model, indicating integrity of the hydrogel and barrier defect, as well as tissue formation following 1-month implantation in rats., Comment: 11 figures, 2 tables, accepted on Acta Biomaterialia

The current management of critical size bone defects (CSBDs) remains challenging and requires multiple surgeries. To reduce the number of surgeries, wrapping a biodegradable fibrous membrane around the defect to contain the graft and carry biological stimulants for repair is highly desirable. Poly(epsilon-caprolactone) (PCL) can be utilised to realise nonwoven fibrous barrier-like structures through free surface electrospinning (FSE). Human periosteum and induced membrane (IM) samples informed the development of an FSE membrane to support platelet lysate (PL) absorption, multipotential stromal cells (MSC) growth, and the prevention of cell migration. Although thinner than IM, periosteum presented a more mature vascular system with a significantly larger blood vessel diameter. The electrospun membrane (PCL3%-E) exhibited randomly configured nanoscale fibres that were successfully customised to introduce pores of increased diameter, without compromising tensile properties. Additional to the PL absorption and release capabilities needed for MSC attraction and growth, PCL3%-E also provided a favourable surface for the proliferation and alignment of periosteum- and bone marrow derived-MSCs, whilst possessing a barrier function to cell migration. These results demonstrate the development of a promising biodegradable barrier membrane enabling PL release and MSC colonisation, two key functionalities needed for the in situ formation of a transitional periosteum-like structure, enabling movement towards single-surgery CSBD reconstruction.

Cell-free translational strategies are needed to accelerate the repair of mineralised tissues, particularly large bone defects, using minimally invasive approaches. Regenerative bone scaffolds should ideally mimic aspects of the tissue's ECM over multiple length scales and enable surgical handling and fixation during implantation in vivo. Leveraging the knowledge gained with bioactive self-assembling peptides (SAPs) and SAP-enriched electrospun fibres, we presented a cell free approach for promoting mineralisation via apatite deposition and crystal growth, in vitro, of SAP-enriched nonwoven scaffolds. The nonwoven scaffold was made by electrospinning poly(epsilon-caprolactone) (PCL) in the presence of either peptide P11-4 (Ac-QQRFEWEFEQQ-Am) or P11-8 (Ac-QQRFOWOFEQQ-Am), in light of the polymer's fibre forming capability and its hydrolytic degradability as well as the well-known apatite nucleating capability of SAPs. The 11-residue family of peptides (P11-X) has the ability to self-assemble into beta-sheet ordered structures at the nano-scale and to generate hydrogels at the macroscopic scale, some of which are capable of promoting biomineralisation due to their apatite-nucleating capability. Both variants of SAP-enriched nonwoven used in this study were proven to be biocompatible with murine fibroblasts and supported nucleation and growth of apatite minerals in simulated body fluid (SBF) in vitro. The fibrous nonwoven provided a structurally robust scaffold, with the capability to control SAP release behaviour. Up to 75% of P11-4 and 45% of P11-8 were retained in the fibres after 7-day incubation in aqueous solution at pH 7.4. The encapsulation of SAP in a nonwoven system with apatite-forming as well as localised and long-term SAP delivery capabilities is appealing as a potential means of achieving cost-effective bone repair therapy for critical size defects.

The design of antibacterial-releasing coatings or wrapping materials with controlled drug release capability is a promising strategy to minimise risks of infection and medical device failure in vivo. Collagen fibres have been employed as medical device building block, although they still fail to display controlled release capability, competitive wet-state mechanical properties, and retained triple helix organisation. We investigated this challenge by pursuing a multiscale design approach integrating drug encapsulation, in-situ covalent crosslinking and fibre spinning. By selecting ciprofloxacin (Cip) as a typical antibacterial drug, wet spinning was selected as a triple helix-friendly route towards Cip-encapsulated collagen fibres; whilst in situ crosslinking of fibre-forming triple helices with 1,3 phenylenediacetic acid (Ph) was hypothesised to yield Ph-Cip {\pi}-{\pi} stacking aromatic interactions and enable controlled drug release. Higher tensile modulus and strength were measured in Ph crosslinked fibres compared to state-of-the-art carbodiimide crosslinked controls. Cip-encapsulated Ph-crosslinked fibres revealed decreased elongation at break and significantly-enhanced drug retention in vitro with respect to Cip-free variants and carbodiimide-crosslinked controls, respectively. This multiscale manufacturing strategy provides new insight aiming at wet spun collagen triple helices with nanoscale-regulated tensile properties and drug release capability.

Photoinduced network formation is an attractive strategy for designing water-insoluble gelatin fibres as medical device building blocks and for enabling late-stage property customisation. However, mechanically-competent, long-lasting filaments are still hard to realise with current photoactive, e.g. methacrylated, gelatin systems due to inherent spinning instability and restricted coagulation capability. To explore this challenge, we present a multiscale approach combining the synthesis of 4-vinylbenzyl chloride (4VBC)-functionalised gelatin (Gel-4VBC) with a voltage-free spinning and UV-curing process so that biopolymer networks in the form of either individual fibres or nonwovens could be successfully manufactured. In comparison to state-of-the-art methacrylated gelatin, the mechanical properties of UV-cured Gel-4VBC fibres were readily modulated by adjustment of coagulation conditions, so that an ultimate tensile strength and strain at break of up to ~80 MPa and ~9 % were measured, respectively. The sequential functionalisation /spinning route proved to be highly scalable, so that one step spunlaid formation of fibroblast-friendly nonwoven fabrics was successfully demonstrated with wet spun Gel-4VBC fibres. The presented approach could be exploited to generate a library of gelatin building blocks tuneable from the molecular to the macroscopic level to deliver computer-controlled extrusion of fibres and nonwovens according to defined clinical applications., Comment: 31 oages, 10 Figures, 2 Supplemental Figures, 3 Tables. To appear in Journal of Materials Science

The covalent functionalisation of type I atelocollagen with either 4-vinylbenzyl or methacrylamide residues is presented as a simple synthetic strategy to achieve customisable, cell-friendly UV-cured hydrogel networks with widespread clinical applicability. Molecular parameters, i.e. the type of monomer, degree of atelocollagen functionalisation and UV curing solution, have been systematically varied and their effect on gelation kinetics, swelling behaviour, elastic properties and enzymatic degradability investigated. UV-cured hydrogel networks deriving from atelocollagen precursors functionalised with equivalent molar content of 4-vinylbenzyl and methacrylamide adducts proved to display remarkably-different swelling ratio, storage modulus and collagenase resistance, similarly to the case of UV-cured hydrogel networks obtained with the same type of methacrylamide adduct, but varied degree of functionalisation. UV-induced network formation of 4VBC functionalised atelocollagen molecules yielded hydrogels with increased stiffness and enzymatic stability, attributed to the molecular rigidity of resulting aromatised crosslinking segment, whilst no toxic response was observed with osteosarcoma G292 cells. Although to a lesser extent, the pH of the UV-curing solution also proved to affect macroscopic hydrogel properties, likely due to the altered organisation of atelocollagen molecules during network formation. By leveraging the knowledge gained with classic synthetic networks, this study highlights how the type of monomer can be conveniently exploited to realise customisable atelocollagen hydrogels with controlled structure-property relationships to meet the requirements of unmet clinical applications., Comment: 10 figures, 2 tables, 3 supplementary figures, Frontiers in Chemistry 2018

Recent advances in massive multiple-input multiple-output (MIMO) communication show that equipping base stations (BSs) with large arrays of antenna can significantly improve the performance of cellular networks. Massive MIMO has the potential to mitigate the interference in the network and enhance the average throughput per user. On the other hand, dynamic time division duplexing (TDD), which allows neighboring cells to operate with different uplink (UL) and downlink (DL) sub-frame configurations, is a promising enhancement for the conventional static TDD. Compared with static TDD, dynamic TDD can offer more flexibility to accommodate various UL and DL traffic patterns across different cells, but may result in additional interference among cells transmitting in different directions. Based on the unique characteristics and properties of massive MIMO and dynamic TDD, we propose a marriage of these two techniques, i.e., to have massive MIMO address the limitation of dynamic TDD in macro cell (MC) networks. Specifically, we advocate that the benefits of dynamic TDD can be fully extracted in MC networks equipped with massive MIMO, i.e., the BS-to-BS interference can be effectively removed by increasing the number of BS antennas. We provide detailed analysis using random matrix theory to show that the effect of the BS-to-BS interference on uplink transmissions vanishes as the number of BS antennas per-user grows infinitely large. Last but not least, we validate our analysis by numerical simulations., Comment: 24 pages, 8 figures

Manuka honey (MH) is used as an antibacterial agent in bioactive wound dressings via direct impregnation onto a suitable substrate. MH provides unique antibacterial activity when compared with conventional honeys, owing partly to one of its constituents, methylglyoxal (MGO). Aiming to investigate an antibiotic-free antimicrobial strategy, we studied the antibacterial activity of both MH and MGO (at equivalent MGO concentrations) when applied as a physical coating to a nonwoven fabric wound dressing. When physically coated on to a cellulosic hydroentangled nonwoven fabric, it was found that concentrations of 0.0054 mg cm-2 of MGO in the form of MH and MGO was sufficient to achieve 100 CFU% bacteria reduction against gram-positive Staphylococcus aureus and gram-negative Klebsiella pneumoniae, based on BS EN ISO 20743:2007. A 3- to 20- fold increase in MGO concentration (0.0170 - 0.1 mg cm-2) was required to facilitate a good antibacterial effect (based on BS EN ISO 20645:2004) in terms of zone of inhibition and lack of growth under the sample. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) was also assessed for MGO in liquid form against three prevalent wound and healthcare-associated pathogens, i.e. Staphylococcus aureus, gram-negative Pseudomonas aeruginosa and gram-positive Enterococcus faecalis. Other than the case of MGO-containing fabrics, solutions with much higher MGO concentrations (128 mg L-1 - 1024 mg L-1) were required to provide either a bacteriostatic or bactericidal effect. The results presented in this study therefore demonstrate the relevance of MGO-based coating as an environment-friendly strategy for the design of functional dressings with antibiotic-free antimicrobial chemistries., Comment: 19 pages, 4 figures, 7 tables. Accepted in Materials

Chitosan (CT) is an antibacterial polysaccharide that has been investigated for drug carriers, haemostats and wound dressings. For these applications, customised CT devices can often be obtained with specific experimental conditions, which can irreversibly alter native biopolymer properties and functions and lead to unreliable material behaviour. In order to investigate the structure-function relationships in CT covalent networks, monosodium 5-sulfoisophthalate (PhS) was selected as heparin-mimicking, growth factor-binding crosslinking segment, whilst 1,4-phenylenediacetic acid (4Ph) and poly(ethylene glycol) bis(carboxymethyl) ether (PEG) were employed as sulfonic acid-free diacids of low and high crosslinker length respectively. Hydrogels based on short crosslinkers (PhS and 4Ph) displayed increased crosslink density, decreased swelling ratio as well as minimal hydrolytic and lysozymic degradation, whilst addition of lysozymes to PEG based networks resulted in 70 wt.-% mass loss. PhS-crosslinked CT hydrogels displayed the highest loss (40 +/- 6 CFU%) of antibacterial activity upon incubation with Porphyromonas gingivalis, whilst respective extracts were tolerated by L929 mouse fibroblasts., Comment: 3 Figures, 1 Table, 1 Supporting Scheme, Materials Letters 2016

Developing successful scaffolds requires clinicians to adopt a multidisciplinary approach in order to understand and stimulate the natural bone regeneration process. A variety of natural and synthetic biomaterials, including naturally extracted, chemically functionalised collagen and synthetic Poly(epsilon-caprolactone) (PCL), can be manufactured into fibres, enabling the formation of nonwoven scaffolds. Many different nonwoven architectures and structural features can then be introduced, depending on the manufacturing parameters. This chapter introduces methods for producing scaffolds with appropriate pore sizes by means of electrospinning, and it outlines the opportunities that exist for other nonwoven manufacturing technologies in the development of biomimetic products., Comment: 4 figures, 1 table, Biomedical Textiles for Orthopaedic and Surgical Applications (book) 2016

Self-assembling peptides (SAPs) have shown to offer great promise in therapeutics and have the ability to undergo self-assembly and form ordered nanostructures. However SAP gels are often associated with inherent weak and transient mechanical properties and incorporation of them into polymeric matrices is a route to enhance their mechanical stability. The aim of this work was to incorporate P11-8 peptide (CH3COQQRFOWOFEQQNH2) within poly(epsilon-caprolactone) (PCL) fibrous webs via one-step electrospinning, aiming to establish the underlying relationships between spinning process, molecular peptide conformation, and material internal architecture. Electrospinning of PCL solutions (6% w/w) in hexafluoro-2-propanol (HFIP) containing up to 40 mg/ml P11-8 resulted in the formation of fibres in both nano- (10-100 nm) and submicron range (100-700 nm), in contrast to PCL only webs, which displayed a predominantly submicron fibre distribution. FTIR and CD spectroscopy on both PCL/peptide solutions and resulting electrospun webs revealed monomeric and beta-sheet secondary conformation, respectively, suggesting the occurrence of peptide self-assembly during electrospinning due to solvent evaporation. The peptide concentration (0 -> 40 mg/ml) was found to primarily affect the internal structure of the fabric at the nano-scale, whilst water as well as cell culture medium contact angles were dramatically decreased. Nearly no cytotoxic response (> 90% cell viability) was observed when L929 mouse fibroblasts were cultured in contact with electrospun peptide loaded samples. This novel nanofibrous architecture may be the basis for an interesting material platform for e.g. hard tissue repair, in light of the presence of the self assembled P11-8 in the PCL fibrous structure., Comment: Journal of Materials Chemistry B 2016

Biomimetic hydrogels based on natural polymers are a promising class of biomaterial, mimicking the natural extra-cellular matrix of biological tissues and providing cues for cell attachment, proliferation and differentiation. With a view to providing an upstream method to guide subsequent experimental design, the aim of this study was to introduce a mathematical model that described the rheological properties of a hydrogel system based on covalently crosslinked collagen triple helices. In light of their organization, such gels exhibit limited collagen bundling that cannot be described by existing fibril network models. The model presented here treats collagen triple helices as discrete semi-flexible polymers, permits full access to metrics for network microstructure, and should provide a comprehensive understanding of the parameter space associated with the development of such multi-functional materials. Triple helical hydrogel networks were experimentally obtained via reaction of type I collagen with both aromatic and aliphatic diacids. The complex modulus G* was found from rheological testing in linear shear and quantitatively compared to model predictions. In silico data from the computational model successfully described the experimental trends in hydrogel storage modulus with either (i) the concentration of collagen triple helices during crosslinking reaction or (ii) the type of crosslinking segment introduced in resulting hydrogel networks. This approach may pave the way to a step change in the rational design of biomimetic triple helical collagen systems with controlled multi-functionality., Comment: 9 figures, 1 scheme, 1 table, ACS Biomaterials Science and Engineering 2016

The design of exudate-managing wound dressings is an established route to accelerated healing, although such design remains a challenge from material and manufacturing standpoints. Aiming towards the clinical translation of knowledge gained in vitro with highly swollen rat tail collagen hydrogels, this study investigated the healing capability in a diabetic mouse wound model of telopeptide-free, protease-inhibiting collagen networks. 4 vinylbenzylation and UV irradiation of type I atelocollagen (AC) led to hydrogel networks with chemical and macroscopic properties comparable to previous collagen analogues, attributable to similar lysine content and dichroic properties. After 4 days in vitro, hydrogels induced nearly 50 RFU% reduction in matrix metalloproteinase (MMP)-9 activity, whilst showing less than 20 wt.-% weight loss. After 20 days in vivo, dry networks promoted 99% closure of 10x10 mm full thickness wounds and accelerated neodermal tissue formation compared to Mepilex. This collagen system can be equipped with multiple, customisable properties and functions key to personalised chronic wound care., Comment: 30 pages, 1 scheme, 6 Figures, 2 Supporting Figures

Self-assembling peptides (SAPs) have the ability to spontaneously assemble into ordered nanostructures enabling the manufacture of "designer" nanomaterials. The reversible molecular association of SAPs has been shown to offer great promise in therapeutics via for example, the design of biomimetic assemblies for hard tissue regeneration. This could be further exploited for novel nano/micro diagnostic tools. However, self-assembled peptide gels are often associated with inherent weak and transient mechanical properties. Their incorporation into polymeric matrices has been considered as a potential strategy to enhance their mechanical stability. This study focuses on the incorporation of an 11-residue peptide, P11-8 (peptide sequence: CH3CO-Gln-Gln-Arg-Phe-Orn-Trp-Orn-Phe-Glu-Gln-Gln-NH2) within a fibrous scaffold of poly ({\epsilon}-caprolactone) (PCL). In this study an electrospinning technique was used to fabricate a biomimetic porous scaffold out of a solution of P11-8 and PCL which resulted in a biphasic structure composed of submicron fibers (diameter of 100-700 nm) and nanofibers (diameter of 10-100 nm). The internal morphology of the fabric and its micro-structure can be easily controlled by changing the peptide concentration. The secondary conformation of P11-8 was investigated in the as-spun fibers by ATR-FTIR spectroscopy and it is shown that peptide self-assembly into \{b}eta-sheet tapes has taken place during fiber formation and the deposition of the fibrous web., Comment: 6 pages, 3 figures, accepted on MRS Advances

Covalent functionalisation of collagen has been shown to be a promising strategy to adjust the mechanical properties of highly swollen collagen hydrogels. At the same time, secondary interactions between for example, amino acidic terminations or introduced functional groups also play an important role and are often challenging to predict and control. To explore this challenge, 4-vinylbenzyl chloride (4VBC) and methacrylic anhydride (MA) were reacted with type I collagen, and the swelling and rheological properties of resulting photo activated hydrogel systems investigated. 4VBC-based hydrogels showed significantly increased swelling ratio, in light of the lower degree of collagen functionalisation, with respect to methacrylated collagen networks, whilst rheological storage moduli were found to be comparable between the two systems. To explore the role of benzyl groups in the mechanical properties of the 4VBC-based collagen system, model chemical force microscopy (CFM) was carried out in aqueous environment with an aromatised probe against an aromatised gold coated glass slide. A marked increase in adhesion force (F: 0.11 +/- 0.01 nN) was measured between aromatised samples, compared to the adhesion force observed between the non-modified probe and a glass substrate (F: 2.64 +/- 1.82 nN). These results suggest the formation of additional and reversible {\pi}-{\pi} stacking interactions in aromatic 4VBC-based networks and explain the remarkable rheological properties of this system in comparison to MA based hydrogels., Comment: 6 pages, 4 figures, accepted in MRS Advances on 3 December 2015

Our goal is to present an elementary approach to the analysis and programming of sparse grid finite element methods. This family of schemes can compute accurate solutions to partial differential equations, but using far fewer degrees of freedom than their classical counterparts. After a brief discussion of the classical Galerkin finite element method with bilinear elements, we give a short analysis of what is probably the simplest sparse grid method: the two-scale technique of Lin et al. (2001). We then demonstrate how to extend this to a multiscale sparse grid method which, up to choice of basis, is equivalent to the hierarchical approach, as described by, e.g., Bungartz and Griebel (2004). However, by presenting it as an extension of the two-scale method, we can give an elementary treatment of its analysis and implementation. For each method considered, we provide MATLAB code, and a comparison of accuracy and computational costs., Comment: 26 pages, 10 figures. Sample code available from http://www.maths.nuigalway.ie/~niall/SparseGrids/

One of the limitations of electrospun collagen as bone-like fibrous structure is the potential collagen triple helix denaturation in the fibre state and the corresponding inadequate wet stability even after crosslinking. Here, we have demonstrated the feasibility of accomplishing wet-stable fibres by wet spinning and diacid-based crosslinking of collagen triple helices, whereby fibre ability to act as bone-mimicking mineralisation system has also been explored. Circular dichroism (CD) demonstrated nearly complete triple helix retention in resulting wet-spun fibres, and the corresponding chemically crosslinked fibres successfully preserved their fibrous morphology following 1-week incubation in phosphate buffer solution (PBS). The presented novel diacid-based crosslinking route imparted superior tensile modulus and strength to the resulting fibres indicating that covalent functionalization of distant collagen molecules is unlikely to be accomplished by current state-of-the-art carbodiimide-based crosslinking. To mimic the constituents of natural bone extra cellular matrix (ECM), the crosslinked fibres were coated with carbonated hydroxyapatite (CHA) through biomimetic precipitation, resulting in an attractive biomaterial for guided bone regeneration (GBR), e.g. in bony defects of the maxillofacial region., Comment: 35 pages, 14 figures, 1 table, 1 scheme (manuscript accepted in "Polymer")

Poly-dl-lactic acid (PDLLA) was blended with type I collagen to attempt to overcome the instantaneous gelation of electrospun collagen scaffolds in biological environments. Scaffolds based on blends of type I collagen and PDLLA were investigated for material stability in cell culture conditions (37 {\deg}C; 5% CO2) in which post-electrospinning glutaraldehyde crosslinking was also applied. The resulting wet-stable webs were cultured with bone marrow stromal cells (HBMSC) for five weeks. Scanning electron microscopy (SEM), confocal laser scanning microscopy (CLSM), Fourier transform infra-red spectroscopy (FTIR) and biochemical assays were used to characterise the scaffolds and the consequent cell-scaffold constructs. To investigate any electrospinning-induced denaturation of collagen, identical PDLLA/collagen and PDLLA/gelatine blends were electrospun and their potential to promote osteogenic differentiation investigated. PDLLA/collagen blends with w/w ratios of 40/60, 60/40 and 80/20 resulted in satisfactory wet stabilities in a humid environment, although chemical crosslinking was essential to ensure long term material cell culture. Scaffolds of PDLLA/collagen at a 60:40 weight ratio provided the greatest stability over a five-week culture period. The PDLLA/collagen scaffolds promoted greater cell proliferation and osteogenic differentiation compared to HMBSCs seeded on the corresponding PDLLA/gelatine scaffolds, suggesting that any electrospinning-induced collagen denaturation did not affect material biofunctionality within 5 weeks in vitro., Comment: 20 pages, 7 figures, 1 table

The formation of naturally-derived materials with wet stable fibrous architectures is paramount in order to mimic the features of tissues at the molecular and microscopic scale. Here, we investigated the formation of wet-spun fibres based on collagen-derived polypeptides with comparable chemical composition and varied molecular weight. Gelatin and hydrolysed fish collagen (HFC) were selected as widely-available linear amino-acidic chains of high and low molecular weight, respectively, and functionalised in the wet-spun fibre state in order to preserve the material geometry in physiological conditions. Wet-spun fibre diameter and morphology were dramatically affected depending on the polypeptide molecular weight, wet-spinning solvent (i.e. 2,2,2-Trifluoroethanol and dimethyl sulfoxide) and coagulating medium (i.e. acetone and ethanol), resulting in either bulky or porous internal geometry. Dry-state tensile moduli were significantly enhanced in gelatin and HFC samples following covalent crosslinking with activated 1,3 phenylenediacetic acid (Ph) (E: 726 +/- 43 - 844 +/- 85 MPa), compared to samples crosslinked via intramolecular carbodiimide-mediated condensation reaction (E: 588 +/- 38 MPa). Resulting fibres displayed a dry diameter in the range of 238 +/- 18 - 355 +/- 28 micron and proved to be mechanically-stable (E: 230 kPa) following equilibration with PBS, whilst a nearly-complete degradation was observed after 5-day incubation in physiological conditions., Comment: 26 pages, 7 figures, 3 tables- accepted in 'International Journal of Biological Macromolecules'

As problems of antibiotic resistance increase, a continuing need for effective bioactive wound dressings is anticipated for the treatment of infected chronic wounds. Naturally derived antibacterial agents, such as Manuka honey, consist of a mixture of compounds, more than one of which can influence antimicrobial potency. The non-peroxide bacteriostatic properties of Manuka honey have been previously linked to the presence of methylglyoxal (MGO). The incorporation of MGO as a functional antibacterial additive during fibre production was explored as a potential route for manufacturing wound dressing components. Synthetic MGO and polyvinyl alcohol (PVA) were fabricated into webs of sub-micron fibres by means of electrostatic spinning of an aqueous spinning solution. Composite fabrics were also produced by direct deposition of the PVA-MGO fibres onto a preformed spunbonded nonwoven substrate. Attenuated Total Reflectance Fourier Transform Infrared (ATR-FTIR) and Proton Nuclear Magnetic Resonance (1H-NMR) spectroscopies confirmed the presence of MGO within the resulting fibre structure. The antibacterial activity of the fibres was studied using strains of Staphylococcus aureus and Escherichia coli. Strong antibacterial activity, as well as diffusion of MGO from the fibres was observed at a concentration of 1.55mg/cm-1., Comment: 13 pages, 5 figurses, 2 tables in Journal of Biomaterials Applications 2015

Biological hydrogels have been increasingly sought after as e.g. wound dressings or scaffolds for regenerative medicine, due to their inherent biofunctionality in biological environments. Especially in moist wound healing, the ideal material should absorb large amounts of wound exudate whilst remaining mechanically competent in-situ. Despite their large hydration, however, current biological hydrogels still leave much to be desired in terms of mechanical properties in physiological conditions. To address this challenge, a multi-scale approach is presented for the synthetic design of cyto-compatible collagen hydrogels with tunable mechanical properties (from nano- up to the macro-scale), uniquely high swelling ratios and retained (>70%) triple-helical features. Type I collagen was covalently functionalized with three different monomers, i.e. 4 vinylbenzyl chloride, glycidyl methacrylate and methacrylic anhydride, respectively. Backbone rigidity, hydrogen-bonding capability and degree of functionalization (F: 16&plusmn12 &ndash 91&plusmn7 mol.-%) of introduced moieties governed the structure-property relationships in resulting collagen networks, so that the swelling ratio (SR: 707&plusmn51 &ndash 1996&plusmn182 wt.-%), bulk compressive modulus (Ec: 30&plusmn7 &ndash 168&plusmn40 kPa) and Atomic Force Microscopy elastic modulus (EAFM: 16&plusmn2 &ndash 387&plusmn66 kPa) were readily adjusted. In light of their remarkably high swelling and mechanical properties, these tunable collagen hydrogels may be further exploited for the design of advanced dressings for chronic wound care., Comment: Accepted in "Journal of the Royal Society Interface"

For the first time in twenty years the U.S. Department of Health and Human Services (DHHS, 2009) is considering changes to federal regulations governing research. The Common Rule provides the basis for government regulations and Institutional Review Boards (IRB). Proposed changes will have a significant impact on Institutional Review Board evaluation of research involving infants, children and adolescents. For example, such a revision can serve to rectify or exacerbate often observed IRB inconsistencies and over-estimation of probable harms when applying "minimal risk" or "exempt" criteria to research involving minors. Proposed revisions may also affect the feasibility of research on adolescent risk that requires waiver of parental or guardian permission to be successfully implemented. Further, recommendations for a new category of "informational risk" based on current and emerging advances in analysis and storage of bio-specimens and information technologies for archival research will have significant influence on ethical procedures required for collection and storage of longitudinal and cross-sectional data. Given the importance of any rule change to the conduct of science related to children, the Society for Research in Child Development (SRCD) convened the SRCD Task Force on Proposed Changes to the Common Rule. The purpose of this report is to alert policymakers, scientists, and participant groups to proposed changes most relevant to research involving children and to provide recommendations for ensuring the responsible conduct of child and adolescent research in the final regulatory changes. (Contains 1 footnote.) [Commentaries by Kenneth D. Pimple and Noreen Yazejian & Barbara Davis Goldman are included. Commentaries are individually referenced.]

Advanced bioactive systems with defined macroscopic properties and spatio-temporal sequestration of extracellular biomacromolecules are highly desirable for next generation therapeutics. Here, chitosan hydrogels were prepared with neutral or negatively-charged crosslinkers in order to promote selective electrostatic complexation with charged drugs. Chitosan (CT) was functionalised with varied dicarboxylic acids, such as tartaric acid (TA), poly(ethylene glycol) bis(carboxymethyl) ether (PEG), 1.4-Phenylenediacetic acid (4Ph) and 5-Sulfoisophthalic acid monosodium salt (PhS), whereby PhS was hypothesised to act as a simple mimetic of heparin. ATR FT-IR showed the presence of C=O amide I, N-H amide II and C=O ester bands, providing evidence of covalent network formation. The crosslinker content was reversely quantified by 1H-NMR on partially-degraded network oligomers, so that 18 mol% PhS was exemplarily determined. Swellability, compressability, material morphology, and drug-loading capability were successfully adjusted based on the selected network architecture. Here, hydrogel incubation with model drugs of varied electrostatic charge, i.e. allura red (AR, --), methyl orange (MO, -) or methylene blue (MB, +), resulted in direct hydrogel-dye electrostatic complexation. Importantly, the cationic compound, MB, showed different incorporation behaviours, depending on the electrostatic character of the selected crosslinker. In light of this tuneable drug-loading capability, these CT hydrogels would be highly attractive as drug reservoirs towards e.g. the fabrication of tissue models in vitro., Comment: Manuscript accepted in Acta Biomaterialia

Chemical crosslinking of collagen is a general strategy to reproduce macroscale tissue properties in physiological environment. However, simultaneous control of protein conformation, material properties and biofunctionality is highly challenging with current synthetic strategies. Consequently, the potentially-diverse clinical applications of collagen-based biomaterials cannot be fully realised. In order to establish defined biomacromolecular systems for mineralised tissue applications, type I collagen was functionalised with 1,3-Phenylenediacetic acid (Ph) and investigated at the molecular, macroscopic and functional levels. Preserved triple helix conformation was observed in obtained covalent networks via ATR-FTIR and WAXS, while network crosslinking degree could be adjusted based on specific reaction conditions. Decreased swelling ratio and increased thermo-mechanical properties were observed compared to state of-the-art carbodiimide (EDC)-crosslinked collagen controls, likely related to the intermolecular covalent incorporation of the aromatic segment. Ph crosslinked hydrogels displayed nearly intact material integrity and only a slight mass decrease following 1-week incubation in either PBS or simulated body fluid (SBF), in contrast to EDC crosslinked collagen. Furthermore, FTIR, SEM and EDS revealed deposition of a calcium-phosphate phase on SBF-retrieved samples, whereby an increased calcium phosphate ratio was observed in hydrogels with higher Ph content. 72-hour material extracts were well tolerated by L929 mouse fibroblasts, whereby cell confluence and metabolic activity (MTS assay) were comparable to those of cells cultured in cell culture medium (positive control). In light of their controlled structure-function properties, these biocompatible collagen hydrogels represent attractive material systems for potential mineralised tissue applications., Comment: Accepted manuscript, Journal of Materials Chemistry B

The design of photo-active collagen systems is presented as a basis for establishing biomimetic materials with varied network architecture and programmable macroscopic properties. Following in-house isolation of type I collagen, reaction with vinyl-bearing compounds of varied backbone rigidity, i.e. 4-vinylbenzyl chloride (4VBC) and glycidyl methacrylate (GMA), was carried out. TNBS colorimetric assay, 1H-NMR and ATR-FTIR confirmed covalent and tunable functionalization of collagen lysines. Depending on the type and extent of functionalization, controlled stability and thermal denaturation of triple helices were observed via circular dichroism (CD), whereby the hydrogen-bonding capability of introduced moieties was shown to play a major role. Full gel formation was observed following photo-activation of functionalized collagen solutions. The presence of a covalent network only slightly affected collagen triple helix conformation (as observed by WAXS and ATR-FTIR), confirming the structural organization of functionalized collagen precursors. Photo-activated hydrogels demonstrated an increased denaturation temperature (DSC) with respect to native collagen, suggesting that the formation of the covalent network successfully stabilized collagen triple helices. Moreover, biocompatibility and mechanical competence of obtained hydrogels were successfully demonstrated under physiologically-relevant conditions. These results demonstrate that this novel synthetic approach enabled the formation of biocompatible collagen systems with defined network architecture and programmable macroscopic properties, which can only partially be obtained with current synthetic methods., Comment: Journal of Materials Chemistry B (2013)

In order to establish defined biomimetic systems, type I collagen was functionalised with 1,3-Phenylenediacetic acid (Ph) as aromatic, bifunctional segment. Following investigation on molecular organization and macroscopic properties, material functionalities, i.e. degradability and bioactivity, were addressed, aiming at elucidating the potential of this collagen system as mineralization template. Functionalised collagen hydrogels demonstrated a preserved triple helix conformation. Decreased swelling ratio and increased thermo-mechanical properties were observed in comparison to state-of-the-art carbodiimide (EDC)-crosslinked collagen controls. Ph-crosslinked samples displayed no optical damage and only a slight mass decrease (~ 4 wt.-%) following 1-week incubation in simulated body fluid (SBF), while nearly 50 wt.-% degradation was observed in EDC-crosslinked collagen. SEM/EDS revealed amorphous mineral deposition, whereby increased calcium phosphate ratio was suggested in hydrogels with increased Ph content. This investigation provides valuable insights for the synthesis of triple helical collagen materials with enhanced macroscopic properties and controlled degradation. In light of these features, this system will be applied for the design of tissue-like scaffolds for mineralized tissue formation., Comment: 2012 MRS Fall Meeting Proceedings

Identifies and discusses six challenges involving the incorporation of sexual orientation issues into the classroom: lack of student exposure to accurate information; selecting a lecture topic; attitudes of intolerance among students; avoiding generalizations; making the topic of sexual orientation relevant to the lives of students; and instructor comfort level concerning the topic. (Contains 58 references and 1 table.) (GCP)

Examined the academic success of children from farm and non-farm families in the rural midwest United States, with a focus on community integration as an important factor for academic achievement. Found that children from farm families showed the highest levels of academic performance, owing largely to the high levels of parental involvement and leadership in the local community. (AA)

Examined possible antecedents of premarital and marital conceptions early in lives of young women (n=5,167) and men (n=5,585). Found that significant antecedents of premarital conception for both sexes were low socioeconomic status; low adolescent social adjustment; and family environment characterized by parent-child arguing, parental divorce or separation, or family history of premarital fertility. (Author/NB)

A method for the fabrication of active semiconductor and high-temperature perconducting devices on the same substrate to form a monolithically integrated semiconductor-superconductor (MISS) structure is disclosed. A common insulating substrate, preferably sapphire or yttria-stabilized zirconia, is used for deposition of semiconductor and high-temperature superconductor substructures. Both substructures are capable of operation at a common temperature of at least 77 K. The separate semiconductor and superconductive regions may be electrically interconnected by normal metals, refractory metal silicides, or superconductors. Circuits and devices formed in the resulting MISS structures display operating characteristics which are equivalent to those of circuits and devices prepared on separate substrates.

A surface plasmon device that operates in a transmissive mode. The light is coupled through optically transparent layers to a surface plasmon which alters the color of the light.

A method for the fabrication of active semiconductor and high-temperature superconducting device of the same substrate to form a monolithically integrated semiconductor-superconductor (MISS) structure is disclosed. A common insulating substrate, preferably sapphire or yttria-stabilized zirconia, is used for deposition of semiconductor and high-temperature superconductor substructures. Both substructures are capable of operation at a common temperature of at least 77 K. The separate semiconductor and superconductive regions may be electrically interconnected by normal metals, refractory metal silicides, or superconductors. Circuits and devices formed in the resulting MISS structures display operating characteristics which are equivalent to those of circuits and devices prepared on separate substrates.

Scattering phenomena are taught in introductory physics classes, and concepts such as conservation of energy and momentum are used at all levels of physics. However, applications of scattering are often not included as part of an education. Rutherford scattering, a topic of any modern physics course, is now used as a tool for materials science applications. In the absence of lab equipment for students to perform such experiments, an exercise in the analysis of scattering data may accent the useful concepts given in lectures. The objective of this exercise is to analyze data from Rutherford backscattering experiments in order to determine elemental composition.

Examined relationships between the Multidimensional Health Locus of Control (MHLC) Scales and subscales of the Minnesota Multiphasic Personality Inventory (MMPI) with inpatients (N=90) at a alcohol treatment unit. Significant correlations were found between dimensions of perceived locus of control and various personality characteristics. (JAC)