Inflammatory dependent bioresponsive smart transdermal delivery system incorporating susppended nanofibrous mats as a platform for wound healing

A thesis submitted to the Faculty of Health Sciences, University of the Witwatersrand, in fulfilment of the requirements for the degree of Doctor of Philosophy Department of Pharmacy and Pharmacology, Faculty of Health Sciences, University of the Witwatersrand, South Africa Johannesburg 2016The perception of wound healing within the current decade goes beyond the straightforward assertion of the three phases assembling the wound healing cascade. Healing of wounds is a complex process that involves a dynamic series of interactions and reactions and requires a collaboration of the many cell pedigrees, mediators and different tissues. The skin is the largest organ of the body and serves as a protective barrier against foreign objects therefore a loss in its veracity may lead to a decrease quality of life or even death. The primary goal for wound care and treatment is an aesthetically pleasing scar with close to complete functionality at the wound site and rapid wound closure. Attainment of these features requires incorporation of various characteristics such as a moisture retention, absorption and debridgement amongst others. A huge variety of wound dressings are available however not all of these meet the specific requirements of an ideal wound healing device to cover every aspect within the wound healing cascade. Highlighted within this thesis is the design and development of a Bioresponsive transdermal delivery system (BTDS) for wound healing that aims at the incorporation of the significant characteristics for optimal wound management and treatment. Nanobiotechnology is an interdisciplinary field that combines many avenues to revolutionise the development of drug delivery systems specific to wound healing. Delivery systems produced on the nanoscale can encourage the promotion of biologically active new molecular entities that were previously considered underdeveloped by the enhancement of the therapeutic efficacy of wound healing materials. Recent research interest has focused on the development of smart biomaterials. Combining biomaterials that are crucial for wound healing will provide opportunities to synthesize matrices that are inductive to cells and that stimulate and trigger target cell responses crucial to the wound healing process. Stimuli responsive systems provides an attractive, novel and alternate approach to the process of healing by offering an advanced alternative to simple wound dressings as they have the ability to adapt to the surrounding wound environment and regulate the healing process by thermal, chemical, biochemical, electrical and mechanical means on exposure to an external stimulus that triggers the effect. The research focused on the development and characteristic analysis of a complete prototyped device for wound healing incorporating a nanofibrous mat as well as a bioresponsive component to inflammation which could be the first novel prototype developed as an inflammation bioresponsive device for superior wound healing incorporating a nanofibrous mat. The BTDS was synthesized by the attainment of a statistically derived Box- Behnken Design Template, whereby 15 formulations were generated to fabricate a wound healing nanofibrous mats as well as a lyophilized inflammatory dependent matrix. The technique entailed the process of electrospinning for nanofiber formation as well as blending and lyophilization for the inflammatory responsive component. Elucidation of the various polymeric and crosslinker concentrations greatly influenced the properties and characteristics of the system. An endorsement in intensity and conjugation is noted by the FTIR spectra whereby greater shifts in wavelengths from 3260.11cm-1 to 3278.79cm-1 is noted when enhancements in crosslinking bridges is undertaken. Structural morphological analysis revealed the synthesis of smooth, cylindrical, uniformly aligned nanofibres without the presence of nanobeads as well as the formation of a lyophilized matrix having a tough backbone structure at higher concentrations. Upon nanotensile mapping, variation in Young‟s Modulus was observed at 4.25MPa providing flexibility whereas a higher Young‟s Modulus provides rigidity and stiffness to the structure. Determination of the bioresponsive nature was carried out in a stimulated inflammatory environment by utilisation of the Fentons reaction: Fe2+ + H2O2 → Fe3+ + OH∙ + OH- . Results amongst the experimentally derived formulations revealed the reliance of bioactive release on the hyaluronic acid concentration and degradation by hydroxyl radicals present. MDT results obtained depicted a value at 42.39 at a higher hyaluronic concentration and degree of crosslinkage whereas at lower concentrations, MDT values at 33.21 and 35.76 were depicted. In vivo histological examination revealed the healing progression whereby the presence of the nanofibrous mat illucidated a close to complete re-epithelisation and remodelling of the wound site represented by thick, vascular granulation tissue dominated by fibroblasts and extensive collagen deposition. The approach of introducing a topical device for wound management containing both nanotechnology and stimuli responsive techniques provide an innovative and encouraging proposal for wound care to the pharmaceutical industry.MT201

Microgravity Science and Applications: Program Tasks and Bibliography for Fiscal Year 1996

NASA's Microgravity Science and Applications Division (MSAD) sponsors a program that expands the use of space as a laboratory for the study of important physical, chemical, and biochemical processes. The primary objective of the program is to broaden the value and capabilities of human presence in space by exploiting the unique characteristics of the space environment for research. However, since flight opportunities are rare and flight research development is expensive, a vigorous ground-based research program, from which only the best experiments evolve, is critical to the continuing strength of the program. The microgravity environment affords unique characteristics that allow the investigation of phenomena and processes that are difficult or impossible to study an Earth. The ability to control gravitational effects such as buoyancy driven convection, sedimentation, and hydrostatic pressures make it possible to isolate phenomena and make measurements that have significantly greater accuracy than can be achieved in normal gravity. Space flight gives scientists the opportunity to study the fundamental states of physical matter-solids, liquids and gasses-and the forces that affect those states. Because the orbital environment allows the treatment of gravity as a variable, research in microgravity leads to a greater fundamental understanding of the influence of gravity on the world around us. With appropriate emphasis, the results of space experiments lead to both knowledge and technological advances that have direct applications on Earth. Microgravity research also provides the practical knowledge essential to the development of future space systems. The Office of Life and Microgravity Sciences and Applications (OLMSA) is responsible for planning and executing research stimulated by the Agency's broad scientific goals. OLMSA's Microgravity Science and Applications Division (MSAD) is responsible for guiding and focusing a comprehensive program, and currently manages its research and development tasks through five major scientific areas: biotechnology, combustion science, fluid physics, fundamental physics, and materials science. FY 1996 was an important year for MSAD. NASA continued to build a solid research community for the coming space station era. During FY 1996, the NASA Microgravity Research Program continued investigations selected from the 1994 combustion science, fluid physics, and materials science NRAS. MSAD also released a NASA Research Announcement in microgravity biotechnology, with more than 130 proposals received in response. Selection of research for funding is expected in early 1997. The principal investigators chosen from these NRAs will form the core of the MSAD research program at the beginning of the space station era. The third United States Microgravity Payload (USMP-3) and the Life and Microgravity Spacelab (LMS) missions yielded a wealth of microgravity data in FY 1996. The USMP-3 mission included a fluids facility and three solidification furnaces, each designed to examine a different type of crystal growth

Muscle activation patterns in shoulder impingement patients

Introduction: Shoulder impingement is one of the most common presentations of shoulder joint problems 1. It appears to be caused by a reduction in the sub-acromial space as the humerus abducts between 60o -120o – the 'painful arc'. Structures between the humeral head and the acromion are thus pinched causing pain and further pathology 2. Shoulder muscle activity can influence this joint space but it is unclear whether this is a cause or effect in impingement patients. This study aimed to observe muscle activation patterns in normal and impingement shoulder patients and determine if there were any significant differences. Method: 19 adult subjects were asked to perform shoulder abduction in their symptomatic arm and non-symptomatic. 10 of these subjects (age 47.9 ± 11.2) were screened for shoulder impingement, and 9 subjects (age 38.9 ± 14.3) had no history of shoulder pathology. Surface EMG was used to collect data for 6 shoulder muscles (Upper, middle and lower trapezius, serratus anterior, infraspinatus, middle deltoids) which was then filtered and fully rectified. Subjects performed 3 smooth unilateral abduction movements at a cadence of 16 beats of a metronome set at 60bpm, and the mean of their results was recorded. T-tests were used to indicate any statistical significance in the data sets. Significance was set at P<0.05. Results: There was a significant difference in muscle activation with serratus anterior in particular showing a very low level of activation throughout the range when compared to normal shoulder activation patterns (<30%). Middle deltoid recruitment was significantly reduced between 60-90o in the impingement group (30:58%).Trends were noted in other muscles with upper trapezius and infraspinatus activating more rapidly and erratically (63:25%; 60:27% respectively), and lower trapezius with less recruitment (13:30%) in the patient group, although these did not quite reach significance. Conclusion: There appears to be some interesting alterations in muscle recruitment patterns in impingement shoulder patients when compared against their own unaffected shoulders and the control group. In particular changes in scapula control (serratus anterior and trapezius) and lateral rotation (infraspinatus), which have direct influence on the sub-acromial space, should be noted. It is still not clear whether these alterations are causative or reactionary, but this finding gives a clear indication to the importance of addressing muscle reeducation as part of a rehabilitation programme in shoulder impingement patients

ECOS 2012

The 8-volume set contains the Proceedings of the 25th ECOS 2012 International Conference, Perugia, Italy, June 26th to June 29th, 2012. ECOS is an acronym for Efficiency, Cost, Optimization and Simulation (of energy conversion systems and processes), summarizing the topics covered in ECOS: Thermodynamics, Heat and Mass Transfer, Exergy and Second Law Analysis, Process Integration and Heat Exchanger Networks, Fluid Dynamics and Power Plant Components, Fuel Cells, Simulation of Energy Conversion Systems, Renewable Energies, Thermo-Economic Analysis and Optimisation, Combustion, Chemical Reactors, Carbon Capture and Sequestration, Building/Urban/Complex Energy Systems, Water Desalination and Use of Water Resources, Energy Systems- Environmental and Sustainability Issues, System Operation/ Control/Diagnosis and Prognosis, Industrial Ecology