Most rural areas of developing countries are faced with problems like shortage of doctors in hospitals, illiteracy and poor power supply. Because of these issues, Information and Communication Technology (ICT) is often sees as a useful solution for these areas. Unfortunately, the social environment is often ignored. This leads to inappropriate systems being developed for these areas. The aims of this thesis were firstly, to learn how a communication system can be built for a rural telehealth environment in a developing country, secondly to learn how users can be supported to use such a system.

Thesis (Ph. D.)--Ohio State University, 2008. / Title from first page of PDF file. Includes bibliographical references (p. 93-103).

Thesis (M.S.)--Rochester Institute of Technology, 2005. / Typescript. Includes bibliographical references (leaves 54-56).

Thesis (Ph. D.)--University of Washington, 2006. / Vita. Includes bibliographical references (leaves 141-152).

Stan N. Finkelstein, Peter Temin. / "October 1982." / Bibliography: p.31-33.

I denna rapport beskrivs hur ett befintligt brainball system har modifierats för att användas på ett så optimalt sätt som möjligt. Brainball är ett spel som går ut på att mäta elektriska hjärnsignaler från två spelare med hjälp av EEG via elektroder som är utplacerade på spelarnas pannor för att kunna avläsa den ständiga elektriska aktiviteten som pågår i hjärnans nervceller. Dessa signaler mäts sedan av en mikroprocessor som jämför hjärnaktiviteten hos båda spelarna och baserat på vem av spelarna som har högst hjärnaktivitet, rullar en stålkula på ett bord mot den spelaren. När stålkulan når hela vägen fram till spelaren med högst hjärnaktivitet får den andra spelaren ett poäng som indikerar att han/hon är mer avslappnad. Genomförandet av detta projekt innehöll dessa följande steg: Felsökning av vad som var fel med det befintliga systemet. Justera/förbättra de elektroniska felen. Utveckla ett förbättringskretskort till systemet. Förbättra det mekaniska systemet. Justera mjukvaran för drivsystemet. Detta projekt utfördes i syfte med att använda systemet i mässor och demonstrationer för att locka studenter till medicinsk teknik. Det viktigaste resultatet som man har kommit fram till är ett fullt fungerande analogt system med förbättringsbar mjukvara. Med det analoga systemet kan man även besvara frågeställningen på hur ögonlocket påverkar avslappningen hos människor. / This report describes how an existing brainball system has been modified to be used in the most optimal way possible. Brainball is a game of measuring two-player electrical brain signals using EEG through electrodes placed on the players' foreheads to read the constant electrical activity going on in the brain's nerve cells. These signals are then measured by a microprocessor that compares the brain activity of both players and based on which of the players that have the highest brain activity, a steel ball rolls on a table towards that player. When the steel ball reaches all the way to the player with the highest brain activity, the other player gets a point indicating that he/she is more relaxed. The implementation of this project included these following steps: Troubleshooting what was wrong with the existing system. Adjust/improve the electronic errors. Develop an enhancement circuit board to the system. Improve the mechanical system. Adjust the software for the drive system. This project is done for the purpose of using the system in exhibitions and demonstrations to attract students to medical technology. The most important result that has been achieved is a fully functional analogue system with improvable software. With the functional analogue system you can also answer the question of how the eyelids affect the relaxation of people.

Cellular microenvironments are an important area of study, and their implications with regard to development, tissue function, and disease, mean that they have particular relevance in tissue engineering. The development of tissue engineered therapeutics is underpinned by the understanding of how the cells exist in their natural environment. A fundamental lack of insight into the signalling mechanisms within microenvironments, due to in part a lack of appropriate technologies, has meant that the therapeutic potential of tissue engineering is limited. To this end, the development of a micropatterning technology that enables control over solute signalling dynamics on the micron scale has been investigated. A bespoke holographic optical tweezers (HOTs) system was used to precisely position cells and controlled release vehicles into three-dimensional arrangements that resemble basic cellular micro-architectures. Via optical manipulation, release vehicles could be patterned to create solute release patterns to mimic signalling events in vitro. A proof of concept was established to demonstrate fluorophore release from microparticles positioned with high precision, into previously unobtainable micron-scale patterns. Such developments required optimisation of the system and protocols, for use with cell and microparticle manipulation and, creating a tool-set suitable for address unsolved biological questions. Biological investigations were completed to demonstrate how the HOTs can be used to control zonal cell differentiation and migration. These processes are paramount to cell microenvironment function, and this study has shown that the HOTs patterning setup is capable of achieving such signalling models in vitro. Herein is presented compelling evidence that optically manipulated release sources can achieve new levels of precision over signalling dynamics, over the length scales suitable for even the smallest cell microenvironments. It is hoped that through the better in vitro modelling of such cellular microenvironments and other signalling events, investigators will be able to elucidate new mechanisms through which cells proliferate and function.

Traumatic spinal cord injury (SCI) is a global health problem involving complex pathophysiological cascade and afflicts both developing and developed countries. Transplantation of Mesenchymal stem cell population such as dental stem cells (DSC) have demonstrated preclinical potential for central nervous system (CNS) repair. The work presented in this thesis has evaluated the potential of dental stem cells from apical papillae (SCAP) in combination with different biomaterials for SCI repair. ECM scaffolds were produced from different mammalian tissues including spinal cord, bone and dental hard tissue using different decellularisation processes. Scaffolds were then digested with pepsin to allow solubilisation and hydrogel formation. The ECM hydrogels were characterised and embedded with SCAP to investigate the effect of morphological and biochemical properties upon cell characteristics. All the hydrogels maintained high cell viability and an increase in the cell number with a satisfactory metabolic activity. However, only ECM hydrogels from decellularised spinal cord and bone tissue supported the expression of neural lineage and pro angiogenic markers with stronger responses observed with spinal cord ECM hydrogels. Biodegradable PLGA-Triblock (PLGA-TB) microparticles were fabricated to provide controlled release of glial cell derived neurotrophic factor (GDNF) and may facilitate SCAP attachment. An optimal PLGA-TB microparticle formulation was selected based on the size, surface morphology and release profile achieved. All commercial preparation of GDNF being stabilised in salt, a modified protocol was required to prepare microparticles. The formulation was modified with 10mM sodium acetate which led to a successful encapsulation and sustained release of bioactive GDNF. To support SCAP attachment and survival, PLGA-TB microparticles surfaces were coated with different ECM pre-gel solutions (spinal cord and bone tissue ECM) and laminin. Assessment of surface coating with ToF-SIMS showed protein adsorption on all the coated microparticles, with a higher adsorption on ECM pre-gel coated microparticles. All the surface modified PLGA-TB microparticles supported prolonged SCAP attachment and survival. Laminin and bone ECM pre-gel coated microparticles promoted a significant increase in SCAP number after 7 days. Over all, the result in this thesis have shown that SCAP combined with decellularised mammalian tissue derived ECM hydrogels or GDNF loaded PLGA-TB microparticles may facilitate delivery of autologous stem cells to promote spinal cord repair.

3D printing is an additive manufacturing technique that is rapidly gaining traction in health and medical applications. This technique could potentially benefit plastic and reconstructive surgeries by fabricating patient-specific tissue replacements with tissue-like functions and mechanical properties. One specific example in the field of plastic and constructive surgery is nose reconstruction. Current gold standard for nasal reconstruction after rhinectomy or severe trauma involves a three stage surgery that requires a minimum of three and maximum of seven operations to achieve an acceptable result. The surgical procedure require transposition of autologous cartilage grafts in conjunction with coverage using an autologous skin flap. Harvest of autologous rib cartilage requires a major additional procedure which creates donor site morbidity. Additionally, major nasal reconstruction also requires sculpting autologous cartilages to form a cartilage framework, which is complex, highly-skill demanding and time-consuming. These drawbacks of the current approach for nasal reconstruction are some of the reasons why facial plastic and reconstructive surgeons are interested in the application of tissue engineering and 3D printing for reconstructive surgeries. To address these clinical challenges, the aim of the work presented in this thesis was to fabricate a personalised 3D bioprinted composite scaffold for nasal reconstruction mimicking the mechanical properties and architecture of nasal cartilage. The composite consists of biodegradable thermoplastic polycaprolactone (PCL) to provide structural support, and cell-laden thermoresponsive and UV crosslinkable gelatin methacrylate (GelMA) to act as a cell carrier. We first investigated the appropriate cell source to use for cartilage tissue engineering and 3D bioprinting. Primary sheep articular chondrocytes (ShCh) and sheep bone marrow derived Mesenchymal Stem Cells (ShMSCs) were isolated, expanded and differentiated; followed by an assessment of the effects of the 3D printing process on cell viability and functionality. From these studies it was observed that ShCh were easier to isolate and expand than ShMSCs because less steps are required and the doubling time is 50% shorter. Additionally, 80% of the ShCh survived the printing process compared to a 50% of the ShMSCs, suggesting that chondrocytes were able to tolerate higher stress caused by the 3D printing process. PCL and poly (lactic-co-glycolic acid) (PLGA) scaffolds were printed and seeded with chondrocytes post-printing. The printing process and the 3D printed structures of these polymers were characterised before and after printing by measuring their molecular weight, thermal and mechanical properties. It was found that the printing process reduced the molecular weight of PLGA by 50% percent due to thermal degradation. Consequently, its glass transition temperature and young’s modulus decreased post printing. On the contrary, PCL’s molecular weight remain unchanged after printing. Characterisation of the chondrocytes showed that whilst both scaffold materials supported cell attachment the ECM secreted deformed the PLGA whilst the PCL scaffolds were unaffected. Due to superior mechanical properties PCL was selected to 3D print the personalised nose scaffolds. Additional studies on the 3D printed scaffolds showed that controlling the surface pores of scaffolds was important for cell infiltration and proliferation Scaffolds with larger surface pores were 3D printed and these resulted in increased cell seeding and proliferation demonstrated by DNA quantification. Moreover, the printing process of the cell carrier GelMA was optimised by utilising its thermoresponsive properties. A rheological study of three different concentrations of GelMA was performed in order to identify the most suitable for bioprinting. GelMA 15% and 20% at 15 °C and 18 °C respectively were found the appropriate ones. Finally, multi-material 3D bioprinting of PCL and chondrocyte-laden GelMA was utilised for making cartilage constructs. The 3D bioprinted constructs showed neocartilage formation and similar mechanical properties to nasal alar cartilage after a 50-day culture period. Neocartilage formation was evidenced by the presence of glycosaminoglycans and collagen type II after cultivation. The findings in this thesis therefore support the feasibility of using 3D bioprinted composite constructs for nasal reconstruction.

The repair of bone defects and non-union fractures is a significant challenge for clinicians as it requires tissue replacement. The current graft approaches used to treat these injuries have limitations with regard to quality and availability. This has resulted in research efforts to develop alternative synthetic materials that are able to aid tissue regeneration. These materials usually combined with biological factors to induce cells proliferation and differentiation. Transcription factors can provide specific regulatory effect, however, these transcription factors are very difficult to be delivered intracellularly. A recent work, conducted at Tissue Engineering group – University of Nottingham, has shown that recombinant transcription factors can be expressed, purified and delivered efficiently to control cell behaviour for further tissue engineering applications. Efficient delivery of these factors can be achieved by using Glycosaminoglycan-binding enhanced transduction (GET) peptides, which are multi-domain peptides comprising a GAG-binding peptide (to promote cell interaction) and a cell-penetrating peptide (CPP) for high efficiency membrane transduction. The aim of the work presented in this thesis was to develop a poly-(lactic-co-glycolic acid) (PLGA) based delivery system to release RUNX2 transcription factor, which is significantly involved in osteogenesis. GET peptide was utilised to enhance the intracellular delivery of RUNX2. The advantage of this system is to control the dose and localisation of the released RUNX2 as well as providing a biodegradable scaffold to support the newly formed tissue. Reproducible procedures were developed to manufacture spherical PLGA microparticles (MPs) using Solid-in-oil-in-water (S/O/W) emulsion method. Red florescent protein (RFP) coupled with GET peptide was used as model protein to evaluate the stability of peptide during microparticles fabrication and release. Efficient encapsulation (~65%) and tailored protein release profiles could be achieved, however intracellular transduction was significantly inhibited post-release. Co-encapsulation of L-Histidine, which may form a complex with the PLGA degradation products under acidic conditions, was used as a strategy to retain GET peptide activity. Simulations of the polymer microclimate showed that hydrolytic acidic PLGA degradation products directly inhibited GET peptide transduction activity, use of L-Histidine significantly enhanced released protein delivery. GET-RUNX2 was efficiently encapsulated (~60%) within PLGA MPs using the developed S/O/W method and release profile was adopted to match the optimal RUNX2 dose needed to induce osteogenesis of hMSCs (i.e. 60μg in the first 7 days of the study). GET-RUNX2 activity post release was evaluated. Results showed comparable transduction and transfection activities (compared to experimental control) throughout the release period. GET-RUNX2 loaded MPs were mixed with temperature-sensitive PLGA/PEG particles to provide scaffold structures. hMSCs were used for an in-vitro differentiation assessments. Osteogenesis gene markers were comparable to experimental controls for both early and late markers. Moreover, the scaffold formula was optimised to be 3D printable to provide complex and irregular shape scaffolds matching defect size. The ability to control intracellular transduction of functional proteins into cells will facilitate localised delivery of therapeutics, with minimised risk of systemic dosing that may lead to non-targeted activity, and allow approaches to direct cellular behaviour for regenerative medicine applications.