Bottom‐Up versus Top‐Down Strategies for Morphology Control in Polymer‐Based Biomedical Materials

The size and shape of polymer materials is becoming an increasingly important property in accessing new functions and applications of nano-/microparticles in many scientific fields. New synthetic methods have allowed unprecedented capability for the facile fabrication of anisotropic and shape-defined nanomaterials. Bottom-up approaches including: emulsion polymerization techniques, amphiphile self-assembly, and polymerization-induced self-assembly, can lead to polymer particles with precise dimensions in the nanoscale. Top-down methods such as lithographic templating, and 3D printing, have increased the access to unique particle shapes. In this review, these recent developments are appraised and contrasted, with future research directions providing that focus on biomedical applications. Finally, the opportunity available for synergistic combinations of top-down and bottom-up fabrication approaches in realizing previously unattainable architectures and material properties is highlighted

The impact of several demographic factors on chemistry laboratory anxiety and self-efficacy in students’ first year of university

The transition from high school to tertiary education can be a daunting prospect for students. The prospect of laboratories, an unfamiliar environment, for students, can increase levels of anxiety. Moreover, there is a growing body of evidence that suggests that students’ self-efficacy is inversely correlated with students’ anxiety. We surveyed students at the start and end of a semester to evaluate levels of anxiety and self-efficacy in relation to several aspects of the chemistry laboratory. Time management and answering assessed questions are the aspects that contribute to high levels of anxiety and low levels of self-efficacy at the start of semester. Students generally reported lower anxiety and higher self-efficacy at the end of the semester about every aspect probed. These results are of interest to any discipline that offers an unfamiliar learning environment for students as aspects such as time management and answering assessed questions are not discipline specific. We investigated the different aspects of anxiety and self-efficacy in relation to various demographic factors

Enhanced Detection of Desmoplasia By Targeted Delivery of Iron Oxide Nanoparticles To the Tumour-Specific Extracellular Matrix

Diagnostic imaging of aggressive cancer with a high stroma content may benefit from the use of imaging contrast agents targeted with peptides that have high binding affinity to the extracellular matrix (ECM). In this study, we report the use of superparamagnetic iron-oxide nanoparticles (IO-NP) conjugated to a nonapeptide, CSGRRSSKC (CSG), which specifically binds to the laminin-nidogen-1 complex in tumours. We show that CSG-IO-NP accumulate in tumours, predominantly in the tumour ECM, following intravenous injection into a murine model of pancreatic neuroendocrine tumour (PNET). In contrast, a control untargeted IO-NP consistently show poor tumour uptake, and IO-NP conjugated to a pentapeptide. CREKA that bind fibrin clots in blood vessels show restricted uptake in the angiogenic vessels of the tumours. CSG-IO-NP show three-fold higher intratumoral accumulation compared to CREKA-IO-NP. Magnetic resonance imaging (MRI) T2-weighted scans and T2 relaxation times indicate significant uptake of CSG-IO-NP irrespective of tumour size, whereas the uptake of CREKA-IO-NP is only consistent in small tumours of less than 3 mm in diameter. Larger tumours with significantly reduced tumour blood vessels show a lack of CREKA-IO-NP uptake. Our data suggest CSG-IO-NP are particularly useful for detecting stroma in early and advanced solid tumours

Using technology to develop transferable skills and enhance the laboratory experience in first year chemistry

Background The laboratory has the potential to be a rich learning environment for students in any science discipline. (Hofstein and Lunetta 2004) The evolving nature of the job market in the 21st century has demanded that graduates leave university equipped with a broad range of generalised attributes. From an early stage in tertiary education, laboratory classes must reflect this need by actively highlighting skills such as: communication, problem solving, critical thinking and teamwork as well as practical competency. Herein lies the problem for educators in that these skills are inherently logistically difficult to assess and require a degree of self-reflection in order to be properly developed. Thus laboratory classes, associated assessments and learning resources must be adapted to provide students with tangible evidence of their development of these skills and to provide opportunities for institutional and self-directed feedback. (Galloway and Bretz 2015) Aims This project aims to develop technology-enhanced methods to highlight and enable students to receive automatic feedback on a particular generic skill that is being assessed in a laboratory. We have two objectives in this project: • To develop pre-laboratory activities which enhance problem solving and critical thinking skills. • To develop a usable, motivating online feedback system to assist students to develop and track practical skills attainment over the course of their unit. Design and methods To evaluate the impact of the pre-laboratory activity students were asked to complete a survey, which aimed to answer the following research questions: • Did the pre laboratory activity prepare students for the laboratory practical? • Did the pre laboratory activity stimulate the students’ curiosity for the laboratory practical? To evaluate the impact of an online feedback system to develop and track practical skills we asked students to complete a survey, which aimed to answer the following research question: • Are the practical laboratory skills (and in-situ recall of practical theory) of students performing recrystallisation experiments improved by providing feedback in the form of online self-directed development exercises before subsequent attempts of those skills? We will also administer interviews with lab demonstrators about the techniques they use to teach and give feedback on practical skills as well as how they perceive students to perform specific tasks and their knowledge of specific practical theory. Results and Conclusion Preliminary data will be presented on two surveys given in semester 1 2016. Results from the first survey indicate that while students feel well prepared for the laboratory, more work is needed to stimulate their curiosity about the experimental procedure. Initial results of the second survey will provide the baseline of knowledge that students have of the recrystallisation laboratory skills in the current format. We will also gain insight from the demonstrators on how they perceive student development of practical skills. We will discuss the direction and approach we are taking in semester 2 2016 based on the preliminary data to improve and integrate feedback and assessment of practical, problem solving and critical thinking skills in the first year chemistry laboratory. References Galloway, K. R. and S. L. Bretz (2015). "Development of an Assessment Tool To Measure Students' Meaningful Learning in the Undergraduate Chemistry Laboratory." Journal of Chemical Education 92(7): 1149-1158. Hofstein, A. and V. N. Lunetta (2004). "The laboratory in science education: Foundations for the twenty-first century." Science Education 88(1): 28-54

Topical Application of an Irreversible Small Molecule Inhibitor of Lysyl Oxidases Ameliorates Skin Scarring and Fibrosis

Scarring is a lifelong consequence of skin injury, with scar stiffness and poor appearance presenting physical and psychological barriers to a return to normal life. Lysyl oxidases are a family of enzymes that play a critical role in scar formation and maintenance. Lysyl oxidases stabilize the main component of scar tissue, collagen, and drive scar stiffness and appearance. Here we describe the development and characterisation of an irreversible lysyl oxidase inhibitor, PXS-6302. PXS-6302 is ideally suited for skin treatment, readily penetrating the skin when applied as a cream and abolishing lysyl oxidase activity. In murine models of injury and fibrosis, topical application reduces collagen deposition and cross-linking. Topical application of PXS-6302 after injury also significantly improves scar appearance without reducing tissue strength in porcine injury models. PXS-6302 therefore represents a promising therapeutic to ameliorate scar formation, with potentially broader applications in other fibrotic diseases

A Perspective on the History and Current Opportunities of Aqueous RAFT Polymerization

Reversible addition-fragmentation chain transfer (RAFT) polymerization has proven itself as a powerful polymerization technique affording facile control of molecular weight, molecular weight distribution, architecture, and chain end groups - while maintaining a high level of tolerance for solvent and monomer functional groups. RAFT is highly suited to water as a polymerization solvent, with aqueous RAFT now utilized for applications such as controlled synthesis of ultra-high molecular weight polymers, polymerization induced self-assembly, and biocompatible polymerizations, among others. Water as a solvent represents a non-toxic, cheap, and environmentally friendly alternative to organic solvents traditionally utilized for polymerizations. This, coupled with the benefits of RAFT polymerization, makes for a powerful combination in polymer science. This perspective provides a historical account of the initial developments of aqueous RAFT polymerization at the University of Southern Mississippi from the McCormick Research Group, details practical considerations for conducting aqueous RAFT polymerizations, and highlights some of the recent advances aqueous RAFT polymerization can provide. Finally, some of the future opportunities that this versatile polymerization technique in an aqueous environment can offer are discussed, and it is anticipated that the aqueous RAFT polymerization field will continue to realize these, and other exciting opportunities into the future

\u3ci\u3eDe novo\u3c/i\u3e Amyloid Peptides With Subtle Sequence Variations Differ In Their Self-Assembly and Nanomechanical Properties

Proteinaceous amyloids are well known for their widespread pathological roles but lately have emerged also as key components in several biological functions. The remarkable ability of amyloid fibers to form tightly packed conformations in a cross β-sheet arrangement manifests in their robust enzymatic and structural stabilities. These characteristics of amyloids make them attractive for designing proteinaceous biomaterials for various biomedical and pharmaceutical applications. In order to design customizable and tunable amyloid nanomaterials, it is imperative to understand the sensitivity of the peptide sequence for subtle changes based on amino acid position and chemistry. Here we report our results from four rationally-designed amyloidogenic decapeptides that subtly differ in hydrophobicity and polarity at positions 5 and 6. We show that making the two positions hydrophobic renders the peptide with enhanced aggregation and material properties while introducing polar residues in position 5 dramatically changes the structure and nanomechanical properties of the fibrils formed. A charged residue at position 6, however, abrogates amyloid formation. In sum, we show that subtle changes in the sequence do not make the peptide innocuous but rather sensitive to aggregation, reflected in the biophysical and nanomechanical properties of the fibrils. We conclude that tolerance of peptide amyloid for changes in the sequence, however small they may be, should not be neglected for the effective design of customizable amyloid nanomaterials

Examining Efficacy of “TAT-less” Delivery of a Peptide against the L‑Type Calcium Channel in Cardiac Ischemia–Reperfusion Injury

Increased calcium influx through the L-type Ca²⁺ channel or overexpression of the alpha subunit of the channel induces cardiac hypertrophy. Cardiac hypertrophy results from increased oxidative stress and alterations in cell calcium levels following ischemia–reperfusion injury and is an independent risk factor for increased morbidity and mortality. We find that decreasing the movement of the auxiliary beta subunit with a peptide derived against the alpha-interacting domain (AID) of the channel attenuates ischemia–reperfusion injury. We compared the efficacy of delivering the AID peptide using a trans-activator of transcription (TAT) sequence with that of the peptide complexed to multifunctional polymeric nanoparticles. The AID-tethered nanoparticles perfused through the myocardium more diffusely and associated with cardiac myocytes more rapidly than the TAT-labeled peptide but had similar effects on intracellular calcium levels. The AID-complexed nanoparticles resulted in a similar reduction in release of creatine kinase and lactate dehydrogenase after ischemia–reperfusion to the TAT-labeled peptide. Since nanoparticle delivery also holds the potential for dual drug delivery, we conclude that AID-complexed nanoparticles may provide an effective platform for peptide delivery in cardiac ischemia–reperfusion injuries

Manipulating directional cell motility using intracellular superparamagnetic nanoparticles

This study investigated the ability for magnetic nanoparticles to influence cellular migration in the presence of an external magnetic field. We found that the direction of migrating keratinocytes can be controlled and the migration speed of fibroblasts can be increased with the internalisation of these nanoparticles in the presence of a magnetic field. The possibility of shepherding cells towards a region of interest through the use of internalized nanoparticles is an attractive prospect for cell tracking, cell therapies, and tissue engineering applications.This work was funded by the Australian Research Council (ARC), and the National Health & Medical Research Council (NHMRC) of Australia. The authors acknowledge the Australian Microscopy & Microanalysis Research Facility at the Centre for Microscopy, Characterisation & Analysis, the University of Western Australia; funded by the University, State and Commonwealth Governments. LG is the beneficiary of a post-doctoral grant from the AXA Research Fund

In vivo imaging and biodistribution of multimodal polymeric nanoparticles delivered to the optic nerve

The use of nanoparticles for targeted delivery of therapeutic agents to sites of injury or disease in the central nervous system (CNS) holds great promise. However, the biodistribution of nanoparticles following in vivo administration is often unknown, and concerns have been raised regarding potential toxicity. Using poly(glycidyl methacrylate) (PGMA) nanoparticles coated with polyethylenimine (PEI) and containing superparamagnetic iron oxide nanoparticles as a magnetic resonance imaging (MRI) contrast agent and rhodamine B as a fluorophore, whole animal MRI and fluorescence analyses are used to demonstrate that these nanoparticles (NP) remain close to the site of injection into a partial injury of the optic nerve, a CNS white matter tract. In addition, some of these NP enter axons and are transported to parent neuronal somata. NP also remain in the eye following intravitreal injection, a non-injury model. Considerable infiltration of activated microglia/macrophages occurs in both models. Using magnetic concentration and fluorescence visualization of tissue homogenates, no dissemination of the NP into peripheral tissues is observed. Histopathological analysis reveals no toxicity in organs other than at the injection sites. Multifunctional nanoparticles may be a useful mechanism to deliver therapeutic agents to the injury site and somata of injured CNS neurons and thus may be of therapeutic value following brain or spinal cord trauma