Investigation of electrophoretic loading and enhanced mechanical properties of hydrogels for delivery of therapeutic proteins

Hydrogels, which are three-dimensional crosslinked hydrophilic polymers, have been used and studied widely as vehicles for drug delivery due to their good biocompatibility. Traditional methods to load therapeutic proteins into hydrogels have some disadvantages. Biological activity of drugs or proteins can be compromised during polymerization process or the process of loading protein can be really timeconsuming. Therefore, different loading methods have been investigated. Based on the theory of electrophoresis, an electrochemical gradient can be used to transport proteins into hydrogels. Therefore, an electrophoretic method was used to load protein in this study. Chemically and radiation crosslinked polyacrylamide was used to set up the model to load protein electrophoretically into hydrogels. Different methods to prepare the polymers have been studied and have shown the effect of the crosslinker (bisacrylamide) concentration on the protein loading and release behaviour. The mechanism of protein release from the hydrogels was anomalous diffusion (i.e. the process was non-Fickian). The UV-Vis spectra of proteins before and after reduction show that the bioactivities of proteins after release from hydrogel were maintained. Due to the concern of cytotoxicity of residual monomer in polyacrylamide, poly(2-hydroxyethyl- methacrylate) (pHEMA) was used as the second tested material. In order to control the pore size, a polyethylene glycol (PEG) porogen was introduced to the pHEMA. The hydrogel disintegrated after immersion in water indicating that the swelling forces exceeded the strength of the material. In order to understand the cause of the disintegration, several different conditions of crosslinker concentration and preparation method were studied. However, the disintegration of the hydrogel still occurred after immersion in water principally due to osmotic forces. A hydrogel suitable for drug delivery needs to be biocompatible and also robust. Therefore, an approach to improving the mechanical properties of the porogen-containing pHEMA hydrogel by introduction of an inter-penetrating network (IPN) into the hydrogel system has been researched. A double network was formed by the introduction of further HEMA solution into the system by both electrophoresis and slow diffusion. Raman spectroscopy was used to observe the diffusion of HEMA into the hydrogel prior to further crosslinking by ã-irradiation. The protein loading and release behaviour from the hydrogel showing enhanced mechanical property was also studied. Biocompatibility is a very important factor for the biomedical application of hydrogels. Different hydrogels have been studied on both a three-dimensional HSE model and a HSE wound model for their biocompatibilities. They did not show any detrimental effect to the keratinocyte cells. From the results reported above, these hydrogels show good biocompatibility in both models. Due to the advantage of the hydrogels such as the ability to absorb and deliver protein or drugs, they have potential to be used as topical materials for wound healing or other biomedical applications.

Hall-petch relationship and strain rate sensitivity of nanocrystalline Mg - 5wt% A1 alloy

This study investigated the grain size dependence of mechanical properties and deformation mechanisms of microcrystalline (mc) and nanocrystalline (nc: grain size below 100 nm) Mg-5wt% Al alloys. The Hall-Petch relationship was investigated by both instrumented indentation tests and compression tests. The test results from the indentation tests and compression tests match well with each other. The breakdown of Hall-Petch relationship and the elevated strain rate sensitivity (SRS) of present Mg-5wt% Al alloys when the grain size was reduced below 58nm indicated the more significant role of GB mediated mechanisms in plastic deformation process. However, the relatively smaller SRS values compared to GB sliding and coble creep process suggested the plastic deformation in the current study is still dislocation mediated mechanism dominant.

Exploration of the defect’s effect on the mechanical properties of different orientated nanowires

Molecular dynamics (MD) simulations have been carried out to investigate the defect’s effect on the mechanical properties of copper nanowire with different crystallographic orientations, under tensile deformation. Three different crystallographic orientations have been considered. The deformation mechanism has been carefully discussed. It is found that the Young’s modulus is insensitive to the defect, even when the nanowire’s crystallographic orientation is different. However, due to the defect’s effect, the yield strength and yield strain appear a large decrease. The defects have played a role of dislocation sources, the slips or stacking faults are first generated around the locations of the defects. The necking locations have also been affected by different defects. Due to the surface defect, the plastic deformation has received a large influence for the <001>/{110} and <110> orientated nanowires, and a relative small influence is seen for the <111> nanowire.

Mechanical properties of cold-formed steels at elevated temperatures

Mechanical properties have an important role in the fire safety design of cold-formed steel structures due to the rapid reduction in mechanical properties such as yield strength and elastic modulus under fire conditions and associated reduction to the load carrying capacities. Hence there is a need to fully understand the deterioration characteristics of yield strength and elastic modulus of cold-formed steels at elevated temperatures. Although past research has produced useful experimental data on the mechanical properties of cold-formed steels at elevated temperatures, such data do not yet cover different cold-formed steel grades and thicknesses. Therefore, an experimental study was undertaken to investigate the elevated temperature mechanical properties of two low and high strength steels with two thicknesses that are commonly used in Australia. Tensile coupon tests were undertaken using a steady state test method for temperatures in the range 20–700 °C. Test results were compared with the currently available reduction factors for yield strength and elastic modulus, and stress–strain curves, based on which further improvements were made. For this purpose, test results of many other cold-formed steels were also used based on other similar studies undertaken at the Queensland University of Technology. Improved equations were developed to predict the yield strength and elastic modulus reduction factors and stress–strain curves of a range of cold-formed steel grades and thicknesses used in Australia. This paper presents the results of this experimental study, comparisons with the results of past research and steel design standards, and the new predictive equations.

High performance additive manufactured scaffolds for bone tissue engineering application

This study demonstrates the feasibility of additive manufactured poly(3-caprolactone)/silanized tricalcium phosphate (PCL/TCP(Si)) scaffolds coated with carbonated hydroxyapatite (CHA)-gelatin composite for bone tissue engineering. In order to reinforce PCL/TCP scaffolds to match the mechanical properties of cancellous bone, TCP has been modified with 3-glycidoxypropyl trimethoxysilane (GPTMS) and incorporated into PCL to synthesize a PCL/TCP(Si) composite. The successful modification is confirmed by X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared spectroscopy (FTIR) analysis. Additive manufactured PCL/TCP(Si) scaffolds have been fabricated using a screw extrusion system (SES). Compression testing demonstrates that both the compressive modulus and compressive yield strength of the developed PCL/TCP(Si) scaffolds fall within the lower ranges of mechanical properties for cancellous bone, with a compressive modulus and compressive yield strength of 6.0 times and 2.3 times of those of PCL/TCP scaffolds, respectively. To enhance the osteoconductive property of the developed PCL/TCP(Si) scaffolds, a CHA-gelatin composite has been coated onto the scaffolds via a biomimetic co-precipitation process, which is verified by using scanning electron microscopy (SEM) and XPS. Confocal laser microscopy and SEM images reveal a most uniform distribution of porcine bone marrow stromal cells (BMSCs) and cellsheet accumulation on the CHA-gelatin composite coated PCL/TCP(Si) scaffolds. The proliferation rate of BMSCs on the CHA-gelatin composite coated PCL/TCP(Si) scaffolds is 2.0 and 1.4 times higher compared to PCL/TCP(Si) and CHA coated PCL/TCP(Si) scaffolds, respectively, by day 10. Furthermore, the reverse transcription polymerase chain reaction (RT-PCR) and western blot analyses reveal that CHA-gelatin composite coated PCL/TCP(Si) scaffolds stimulate osteogenic differentiation of BMSCs the most compared to the other scaffolds. In vitro results of SEM, confocal microscopy and proliferation rate also show that there is no detrimental effect of GPTMS modification on biocompatibility of the scaffolds.

Psychometric properties of the parents' fever management scale in a Turkish population

Aim: This paper reports a study designed to assess the psychometric properties (validity and reliability) of a Turkish version of the Australian Parents’ Fever Management Scale (PFMS). Background: Little is known about childhood fever management among Turkish parents. No scales to measure parents’ fever management practices in Turkey are available. Design: This is a methodological study. Methods: Eighty parents, of febrile children aged six months to five years, were randomly selected from the paedaitric hospital and two community family health centers in Sakarya, Turkey. The PFMS was back translated; language equivalence and content validity were validated. PFMS and socio-demographic data were collected in 2009. Means and standard deviations were calculated for interval level data and p values greater than 0.05 were considered statistically significant. Unrotated principal component analysis was used to determine construct validity and Cronbach’s coefficient alpha determined the internal consistency reliability. Results: The PFMS was psychometrically sound in this population. Construct validity, confirmed by confirmatory factor analysis [KMO 0.812, Bartlett’s Specificity (χ² = 182.799, df=28, P < 0·001)] revealed the Turkish version to be comprised of the eight original PFMS items. Internal consistency reliability coefficient was 0.80 and the scale’s total-item correlation coefficients ranged from 0.15 to 0.66 and were significant (p<0.001). Interestingly parents reported high scores on the PFMS 34.52±4.60 (range 8-40 with 40 indicating a high burden of care for febrile children). Conclusion: The PFMS was as psychometrically robust in a Turkish population as in an Australian population and is, therefore, a useful tool for health professionals to identify parents’ practices, provide targeted education thereby in reducing the unnecessary burden of care they place on themselves when caring for a febrile child. Relevance to clinical practice. Testing in different populations, cultures and healthcare systems will further assist in reporting the PFMS usefulness in clinical practice and research.

Shifting : one-inclusion mistake bounds and sample compression

We present new expected risk bounds for binary and multiclass prediction, and resolve several recent conjectures on sample compressibility due to Kuzmin and Warmuth. By exploiting the combinatorial structure of concept class F, Haussler et al. achieved a VC(F)/n bound for the natural one-inclusion prediction strategy. The key step in their proof is a d = VC(F) bound on the graph density of a subgraph of the hypercube—oneinclusion graph. The first main result of this paper is a density bound of n [n−1 <=d-1]/[n <=d] < d, which positively resolves a conjecture of Kuzmin and Warmuth relating to their unlabeled Peeling compression scheme and also leads to an improved one-inclusion mistake bound. The proof uses a new form of VC-invariant shifting and a group-theoretic symmetrization. Our second main result is an algebraic topological property of maximum classes of VC-dimension d as being d contractible simplicial complexes, extending the well-known characterization that d = 1 maximum classes are trees. We negatively resolve a minimum degree conjecture of Kuzmin and Warmuth—the second part to a conjectured proof of correctness for Peeling—that every class has one-inclusion minimum degree at most its VCdimension. Our final main result is a k-class analogue of the d/n mistake bound, replacing the VC-dimension by the Pollard pseudo-dimension and the one-inclusion strategy by its natural hypergraph generalization. This result improves on known PAC-based expected risk bounds by a factor of O(logn) and is shown to be optimal up to an O(logk) factor. The combinatorial technique of shifting takes a central role in understanding the one-inclusion (hyper)graph and is a running theme throughout.

Corrigendum to “Shifting : one-inclusion mistake bounds and sample compression” [J. Comput. System Sci. 75 (1) (2009) 37–59]

H. Simon and B. Szörényi have found an error in the proof of Theorem 52 of “Shifting: One-inclusion mistake bounds and sample compression”, Rubinstein et al. (2009). In this note we provide a corrected proof of a slightly weakened version of this theorem. Our new bound on the density of one-inclusion hypergraphs is again in terms of the capacity of the multilabel concept class. Simon and Szörényi have recently proved an alternate result in Simon and Szörényi (2009).

Shifting : one-inclusion mistake bounds and sample compression

We present new expected risk bounds for binary and multiclass prediction, and resolve several recent conjectures on sample compressibility due to Kuzmin and Warmuth. By exploiting the combinatorial structure of concept class F, Haussler et al. achieved a VC(F)/n bound for the natural one-inclusion prediction strategy. The key step in their proof is a d=VC(F) bound on the graph density of a subgraph of the hypercube—one-inclusion graph. The first main result of this report is a density bound of n∙choose(n-1,≤d-1)/choose(n,≤d) < d, which positively resolves a conjecture of Kuzmin and Warmuth relating to their unlabeled Peeling compression scheme and also leads to an improved one-inclusion mistake bound. The proof uses a new form of VC-invariant shifting and a group-theoretic symmetrization. Our second main result is an algebraic topological property of maximum classes of VC-dimension d as being d-contractible simplicial complexes, extending the well-known characterization that d=1 maximum classes are trees. We negatively resolve a minimum degree conjecture of Kuzmin and Warmuth—the second part to a conjectured proof of correctness for Peeling—that every class has one-inclusion minimum degree at most its VC-dimension. Our final main result is a k-class analogue of the d/n mistake bound, replacing the VC-dimension by the Pollard pseudo-dimension and the one-inclusion strategy by its natural hypergraph generalization. This result improves on known PAC-based expected risk bounds by a factor of O(log n) and is shown to be optimal up to a O(log k) factor. The combinatorial technique of shifting takes a central role in understanding the one-inclusion (hyper)graph and is a running theme throughout