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Industry 4.0 : Cyber-Physical Systems and their impact on Business Models. / Industri 4.0 : Cyber-Physical Systems och deras påverkan på Affärsmodeller.Åkeson, Linus January 2016 (has links)
Industry 4.0 is one of the fastest growing topics amongst both practitioners and academics. To this day, no definition of Industry 4.0 has reached consensus. However, some definitions can be considered more correct than others and the most accurate one is summarized as “Industry 4.0 is a concept for creating value throughout the whole value-chain”. This has been made possible through digital solutions, advanced technologies, which often are associated with Industry 4.0. This thesis started off finding the key aspects of Industry 4.0 and through a literature review it was concluded to be Cyber-Physical Systems (CPS) which will bring new innovative Business Models. The fundamental aspect of Industry 4.0 is data, data which has become available through the usage of CPS, data which will transform how business are conducted. This thesis aims to develop a better understanding for how CPS affects the Business Model. The thesis started with a literature review, investigating the value of information in a digitalized era. It was established that the value is found in the capability to monitor, remote control, optimize, and automate products and machines. Furthermore, it was also established through the literature review that manufacturing industries are becoming more services-focused and that value-creation is done through networking. Moreover, the Business Model Canvas was embraced as theoretical framework for what a business model should consist of. Data was gathered through semi-structured interviews with experts on the subject of Industry 4.0 and digitalization. The data was then compared to the theoretical framework. The results showed that CPS will not affect business models in any direct way as it is very well founded that the business model always should be based on the customer segment. However, CPS did have an indirect impact on business models i.e. through expected changes in customer relationships and distribution channels, but foremost, through changes regarding specialization and partnerships.
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The Business Model of Biotech SMEs : How do biotech SMEs cope with the industry’s challenges?Tölle, Julian, Kappfjell Herbst, Fransisca January 2016 (has links)
The purpose of this study was to investigate how biotech SMEs structure their business model to deal with the industry’s challenges. The first step was to lay a theoretical foundation of the business model and clarify ambiguities surrounding the business model concept. This lead to the Business Model Canvas, which was used as tool of analysis for this thesis. Semi-structured interviews were then conducted with companies, experts and cluster managers, following the nine building blocks of the Business Model Canvas. The results showed that two typologies of business models could be seen, which we divided in pharmaceutical biotech SMEs and non-pharmaceutical biotech SMEs. Both business models face challenges of research and development process, but to different degrees. Pharmaceutical biotech SMEs deal with long, costly and risky research process, which results in a research-centered business model. During the research period, these companies don’t generate revenues through sales. Non-pharmaceutical biotech SMEs on the other hand, face less harsh research and development processes, which allows them to market their products faster and generate revenue from sales. This results in a more customer-centric business model than the pharmaceutical biotech SMEs.
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Att designa ett slutet kretslopp : En kvalitativ studie kring hur design kan underlätta implementeringen av en cirkulär affärsmodell i detaljhandelnGrönlund, Felicia, Loheim Hammarberg, Li January 2019 (has links)
Dagens ekonomiska system bygger på en linjär modell där varor produceras, används och sedan slängs. Den linjära modellen tillsammans med en ökad befolkningsmängd som överkonsumerar planetens begränsade resurser, har bidragit till att mängden avfall och miljöproblem ständigt ökar. En cirkulär ekonomi presenteras i forskningen som ett avgörande steg mot ett mer hållbart samhälle. I en cirkulär ekonomi tillvaratas material och resurser i förlängda livscykler, vilket kan liknas vid ett slutet kretslopp. Uppsatsen är en kvalitativ studie med syfte att skapa en förståelse för vad sex företag i detaljhandeln har för uppfattning kring cirkulära affärsmodeller samt redogöra för hur väl anpassade deras affärsmodeller är till en cirkulär ekonomi. Studien ämnar även undersöka på vilket sätt design kan bidra till en mer cirkulär affärsmodell. Datainsamlingen har genomförts via semistrukturerade intervjuer med åtta respondenter, varav sex stycken var med grundare eller medgrundare av företag i detaljhandeln som arbetar med cirkulära arbetsmetoder. Empirin har analyserats utifrån den teoretiska referensramen, som bygger på tidigare forskning kring cirkulär ekonomi, cirkulära affärsmodeller, designtänkande och ekodesign. Studien visar att kunskapen kring begreppet cirkulär ekonomi är relativt låg, att de studerade företagen har delvis cirkulära affärsmodeller, men att det finns många utvecklingsområden för att uppnå ett helt cirkulärt flöde. Studiens resultat pekar på att design kan bidra med verktyg för att utforma mer hållbara strategier och lösningar på de hinder som finns i implementeringsprocessen av en cirkulär affärsmodell.
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Estabelecimento de startups: proposta de framework cíclico para geração e refinamento de conceitos e estruturação da operação inicial de negócios inovadores. / .Farina, Diane Aparecida dos Reis Silva 22 March 2017 (has links)
Atualmente as organizações enfrentam grandes desafios como por exemplo a necessidade de reduzir o ciclo de vida de produtos e serviços, enfrentar exigências de qualidade superiores, menores tempo de desenvolvimento e menores custos de produção, devendo buscar a excelência produtiva mas, contraditoriamente também sendo cobradas pelo desenvolvimento de inovações e pela busca de maior agilidade. Neste cenário verifica-se o aumento na importância das startups, organizações que exploram novas oportunidades no mercado e que apresentam grande potencial para geração de inovações radicais. Apesar do aumento da sua relevância, ainda existem poucos modelos elaborados e validados, capazes de auxiliar estas organizações em seu processo inicial de estruturação de operação. Como consequência, atualmente as startups podem adotar técnicas inadequadas à sua realidade, reconhecidamente burocráticas, inflexíveis e pouco inovadoras. Buscando reduzir esta lacuna de conhecimento este estudo propõe um Framework Cíclico que visa contribuir com as startups em seu processo de geração e refinamento de conceitos e na estruturação inicial da sua operação, tendo como objetivo facilitar o atingimento do sucesso. Para o seu desenvolvimento inicialmente foi realizada ampla revisão bibliográfica, resultando numa primeira versão do Framework. Esta versão foi utilizada para a realização de dois estudos de caso que, em conjunto com a qualificação, resultou em alterações no seu layout porém manteve suas características essenciais. Uma segunda versão do Framework Cíclico foi avaliada em um painel que contou com a participação de 8 especialistas em startups, profissionais conceituados cujas observações foram analisadas utilizando de Análise Qualitativa, resultando numa mudança de etapa no Framework, incorporando o Canvas do Value Proposition Design e algumas contribuições no detalhamento das etapas. Com a terceira versão do Framework estruturada foi realizada uma survey que contou com a participação de 88 empreendedores de startups consideradas de sucesso. Para isto, de forma a estabelecer a amostra da pesquisa foram selecionadas startups com existência de mais de um ano, já aceleradas ou em processo de aceleração em aceleradoras brasileiras. Os resultados obtidos foram trabalhados com aplicação de Análise Qualitativa e Análise Fatorial e, como resultados, ocorreu a mudança de posicionamento de uma etapa, além da contribuições que destacam alguns pontos de atenção no desenvolvimento das diferentes etapas. Assim, foi obtida a versão final do Framework Cíclico, correspondendo ao objetivo proposto para este estudo, auxiliar na geração e refinamento de conceitos e estruturação da operação inicial de negócios inovadores. / Currently organizations face major challenges such as the need to reduce product and service life cycles, to obtain higher quality standards and lower production costs, aiming to obtain excellence in production but, contradictorily, aiming to develop significant innovations and to foster more agility. In this scenario it is possible to observe the growing importance of startups, emerging companies that explore new market opportunities and have big potential for the generation of radical innovations. Despite the increase of their relevance, until now there are few structured and validated models, capable of contributing with these organizations in their initial phases. As a consequence, currently startups can only adopt techniques that are inadequate to their reality since they are bureaucratic, inflexible and little innovative. Aiming to reduce this gap of knowledge, this research proposes a Cyclic Framework that aims to contribute with the startups in their process of generation and refinement of concepts and in the initial structuration of its operation, in order to facilitate the achievement of success. For the development of the first version an extensive literature review was performed. This version of the Framework was applied in two case studies that, in conjunction with the qualification, resulted in changes in the layout of the Framework but maintained its essencial characteristics. This second version of the Cyclic Framework was evaluated in a panel that counted with the participation of 8 specialists in startups, recognized professionals whose observations have been analyzed with the application of qualitative analysis. As a result a stage changed in Framework, including Canvas of Value Proposition Design and some other contributions were incorporated into the detailed steps of the Framework. Considering this third version of the Framework structured and validated, a final survey was performed and 88 entrepreneurs of startups participated. The sample for this research was selected at startups with existence of more than one year, that are already accelerated or in acceleration process at Brazilian accelerators. The obtained results were analyzed with the application of Qualitative Analysis and quantitative Factor Analysis and, as results, there was a change in the position of a step and the improvement of points of attention in the development of different steps. As a result the final version of the Cyclic Framework was developed and the main objective of this study was obtained, the development of a tool to contribute in the generation and improvement of concepts and structuring in the initial operation of innovative businesses.
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Understanding the business model in the video game industry : A case study on an independent video game developerEriksson, Gustav, Almér, Erik January 2019 (has links)
Background: Tough competition, time- and resource constraints, and changing consumer demands in the video game industry requires business models that can cope with the pressure. Purpose: The purpose of this thesis is to use business model framework in order to better understand how independent video game developers develop their business models. We aim to contribute to the development of business model literature within the context of independent video game development by further the understanding of how a business model framework can be utilized in this new context. Method: A case study method was used, focusing on a single-case and interviews with participants from the case company. Conclusion: We further develop the BMC by proposing to divide the BMC for independent video game developers into a pre-release and post-release BMC to better describe the business model for an independent video game developer and the business model evolution from pre-release to post-release.
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Estabelecimento de startups: proposta de framework cíclico para geração e refinamento de conceitos e estruturação da operação inicial de negócios inovadores. / .Diane Aparecida dos Reis Silva Farina 22 March 2017 (has links)
Atualmente as organizações enfrentam grandes desafios como por exemplo a necessidade de reduzir o ciclo de vida de produtos e serviços, enfrentar exigências de qualidade superiores, menores tempo de desenvolvimento e menores custos de produção, devendo buscar a excelência produtiva mas, contraditoriamente também sendo cobradas pelo desenvolvimento de inovações e pela busca de maior agilidade. Neste cenário verifica-se o aumento na importância das startups, organizações que exploram novas oportunidades no mercado e que apresentam grande potencial para geração de inovações radicais. Apesar do aumento da sua relevância, ainda existem poucos modelos elaborados e validados, capazes de auxiliar estas organizações em seu processo inicial de estruturação de operação. Como consequência, atualmente as startups podem adotar técnicas inadequadas à sua realidade, reconhecidamente burocráticas, inflexíveis e pouco inovadoras. Buscando reduzir esta lacuna de conhecimento este estudo propõe um Framework Cíclico que visa contribuir com as startups em seu processo de geração e refinamento de conceitos e na estruturação inicial da sua operação, tendo como objetivo facilitar o atingimento do sucesso. Para o seu desenvolvimento inicialmente foi realizada ampla revisão bibliográfica, resultando numa primeira versão do Framework. Esta versão foi utilizada para a realização de dois estudos de caso que, em conjunto com a qualificação, resultou em alterações no seu layout porém manteve suas características essenciais. Uma segunda versão do Framework Cíclico foi avaliada em um painel que contou com a participação de 8 especialistas em startups, profissionais conceituados cujas observações foram analisadas utilizando de Análise Qualitativa, resultando numa mudança de etapa no Framework, incorporando o Canvas do Value Proposition Design e algumas contribuições no detalhamento das etapas. Com a terceira versão do Framework estruturada foi realizada uma survey que contou com a participação de 88 empreendedores de startups consideradas de sucesso. Para isto, de forma a estabelecer a amostra da pesquisa foram selecionadas startups com existência de mais de um ano, já aceleradas ou em processo de aceleração em aceleradoras brasileiras. Os resultados obtidos foram trabalhados com aplicação de Análise Qualitativa e Análise Fatorial e, como resultados, ocorreu a mudança de posicionamento de uma etapa, além da contribuições que destacam alguns pontos de atenção no desenvolvimento das diferentes etapas. Assim, foi obtida a versão final do Framework Cíclico, correspondendo ao objetivo proposto para este estudo, auxiliar na geração e refinamento de conceitos e estruturação da operação inicial de negócios inovadores. / Currently organizations face major challenges such as the need to reduce product and service life cycles, to obtain higher quality standards and lower production costs, aiming to obtain excellence in production but, contradictorily, aiming to develop significant innovations and to foster more agility. In this scenario it is possible to observe the growing importance of startups, emerging companies that explore new market opportunities and have big potential for the generation of radical innovations. Despite the increase of their relevance, until now there are few structured and validated models, capable of contributing with these organizations in their initial phases. As a consequence, currently startups can only adopt techniques that are inadequate to their reality since they are bureaucratic, inflexible and little innovative. Aiming to reduce this gap of knowledge, this research proposes a Cyclic Framework that aims to contribute with the startups in their process of generation and refinement of concepts and in the initial structuration of its operation, in order to facilitate the achievement of success. For the development of the first version an extensive literature review was performed. This version of the Framework was applied in two case studies that, in conjunction with the qualification, resulted in changes in the layout of the Framework but maintained its essencial characteristics. This second version of the Cyclic Framework was evaluated in a panel that counted with the participation of 8 specialists in startups, recognized professionals whose observations have been analyzed with the application of qualitative analysis. As a result a stage changed in Framework, including Canvas of Value Proposition Design and some other contributions were incorporated into the detailed steps of the Framework. Considering this third version of the Framework structured and validated, a final survey was performed and 88 entrepreneurs of startups participated. The sample for this research was selected at startups with existence of more than one year, that are already accelerated or in acceleration process at Brazilian accelerators. The obtained results were analyzed with the application of Qualitative Analysis and quantitative Factor Analysis and, as results, there was a change in the position of a step and the improvement of points of attention in the development of different steps. As a result the final version of the Cyclic Framework was developed and the main objective of this study was obtained, the development of a tool to contribute in the generation and improvement of concepts and structuring in the initial operation of innovative businesses.
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Zjišťování dopadu disruptivních business modelů na české outgoingové cestovní kanceláře / Assessing the impact of disruptive business models on the Czech outbound travel agencyChreno, Petr January 2017 (has links)
The diploma thesis focuses on the identification of the impact of disruptive models in tourism at the Czech travel operators. The theoretical part describes the business model using the canvas method. Subsequently, various patterns of disruptive business models in tourism market are presented. In the practical part, a research was carried out to find out how Czech citizens use disruptive models for traveling abroad. Based on the results of research in the context of different areas, the impact of disruptive models on travel operators was assessed. This work did not confirm the direct negative impact of these models on the growth of Czech travel agencies, but points out the future threat that these disruptive models will introduce in the years to come
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Bringing together engineering and entrepreneurship: understanding the role of tethered C-CHY1 in the fight against antimicrobial resistanceAlexander, Todd E. 06 August 2019 (has links)
Healthcare associated infections (HAIs) cost the US healthcare system over $45 billion to treat and cause millions of deaths annually. A large subset of HAIs are associated with medical devices that are meant to improve and save lives. Infected devices are treated using traditional antibiotics, contributing to development of antibiotic resistance. Antibiotic resistance is expected to cost $100 trillion and kill more people a year than cancer by 2050; thus, new alternative antimicrobials for the treatment of device-associated HAIs are critically needed. Antimicrobial peptides (AMPs), such as 26 amino-acid (aa), marine-derived Chrysophsin-1 (CHY1), are poised to reduce HAIs due to their broad antimicrobial activity and unique mechanisms of action that do not promote bacterial resistance. AMPs are short (12-50aa), positively charged (+2-+9) proteins found in the innate immune systems of many different species. Their high separation of hydrophilic and hydrophobic residues leads to many unique mechanisms derived from many unique secondary and tertiary structures that are not yet well understood. Despite the discovery of over 2000 natural AMPs and many more synthetically designed AMPs, none have been successfully commercialized for healthcare applications due to challenges surrounding cytotoxicity, short in vivo half-life (degradation), high costs of production and effectiveness in physiological environments (such as those with high-salt). Several strategies have been investigated to overcome these challenges, for example, truncation of cytotoxic sequences or D-amino acid substitution to improve AMP toxicity and stability; however, many of these strategies can reduce antimicrobial effectiveness. A unique strategy of increasing stability, reducing cytotoxicity, and maintaining antimicrobial activity that is relevant for medical devices is the covalent tethering (binding) of AMPs via a flexible tethering molecule to the surface. However, the effect of tethering parameters on resulting AMP mechanisms and activity is still widely debated. AMP activity can vary widely by utilizing different tethering strategies, which include additional variables such as: (1) peptide choice and properties (such as native mechanism, concentration, charge, and structure), (2) tether choice and properties (such as chemical composition, length, charge, surface density, and flexibility), and (3) testing conditions (such as temperature, solvent composition and substrate type). Some studies suggest that AMP performance may be tether-dependent, for example some AMPs require longer tethers while others do not and some need a flexible tether. Thus, models for predicting successful tethering strategies for different AMP properties, which currently do not exist, must be developed. Further, complicated and often destructive techniques, such as XPS and SEM, are typically implemented to study the relationship of all these parameters vs. antimicrobial activity, which are labor-intensive and limited in scope. Predictive models guiding tether strategy need to be constructed, but also new techniques to study tethering be developed. If these technical milestones are achieved they can serve as a predicate for commercial implementation of a host of new therapies targeted at reducing device-associated HAIs. The overall goal of this thesis was to study the relationship between antimicrobial activity of tethered C-CHY1 examining both spacer length and peptide surface density and the development of a feasible clinical business case for tethered AMPs. To achieve this goal, a traditional entrepreneurial approach was taken in which a minimally-viable product was first designed and business case analyzed, followed by studies to better optimize and understand the underlying structure-mechanism relationships. CHY1 with a C-terminus cysteine to allow for surface-binding (C-CHY1) was tethered onto a silicon dioxide surface via a flexible poly(ethylene glycol) (PEG) tether, and then both surface binding behavior and antimicrobial success of C-CHY1 were examined as a function of tether properties and reaction conditions. For these studies, quartz-crystal microbalance with dissipation (QCM-D) was the primary technique, a real-time, non-destructive flow method that was then coupled with downstream characterization techniques: fluorescent microscopy and contact angle measurements. In parallel a deep dive into domestic and international business models for commercializing AMP technologies. Specifically, tether length and surface density effects on C-CHY1 mechanisms were studied, followed by the effect of temperature, type of microbe, and salt concentration on the antimicrobial mechanisms of tethered C-CHY1. QCM-D was used to measure binding of C-CHY1 via three different length tethers, PEG molecular weight (MW) 866, 2000 and 7500, followed by microscopy to measure antimicrobial effectiveness against two model microbes Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). Modeling of QCM-D data allowed for surface density and thickness to be calculated and related to C-CHY1 antimicrobial activity. PEG 7500 allowed proper C-CHY1 orientation and mobility, allowing for its native pore-forming mechanism and highest activity while PEG 866 tethers led to denser grafting and an effective, yet non-native ion displacement mechanism. The QCM-D was used to characterize the effect of salt concentration and temperature reaction conditions on the grafting density of C-CHY1 tethered via PEG 866 and PEG 7500, which was then related to antimicrobial activity. For PEG MW 866, neither temperature nor salt concentration increases significantly altered the grafting density of C-CHY1 while for PEG 7500 increasing temperature allowed for significantly increased grafting density. C-CHY1 density had no significant effect on antimicrobial activity against either microbe. Temperature of bacterial incubation did demonstrate microbe-specific changes in C-CHY1 antimicrobial activity. These results demonstrated that small changes in reaction conditions can drastically change membrane selectivity of C-CHY1. An in-depth investigation of the effects of bacterial membrane composition and temperature on soluble C-CHY1 mechanism was implemented to better understand the molecular membrane- and temperature-dependent selectivity and structure-function of C-CHY1. Supported lipid bilayers (SLBs) formed in QCM-D can be used as model membranes to elucidate AMP action mechanisms against membranes of different compositions. Two and three component SLBs representative of Gram-negative phosphatidylethanolamine (PE) and phosphatidyglycerol acid (PG) with and without charged lipopolysaccharide, LPS and Gram-positive bacteria phosphatidylcholine (PC) and PG with and without charged lipoteichoic acid, (LTA) were formed at both 23°C and 37°C. C-CHY1 at 5 µM was exposed to the different membranes and mechanistic surface action was studied. The membranes formed highly different baseline responses in QCM-D, indicative of vastly different membrane structures, thicknesses and deposition behaviors on SiO2, warranting future studies. Further, significant effects of LTA incorporation were observed in both peptide interaction and deposition. There were measurable effects of temperature on membrane formation as well as peptide interaction kinetics and even mode of interaction. Lastly, business models for the commercialization of novel medical device technologies such as surface-tethered C-CHY1 were investigated. While this technology has the potential to solve many unmet needs, there must a commercialization plan implemented in order to have an impact. There is a clear disconnect between technology development in academia and technology commercialization in industry that must be connected. Development of an entrepreneurial mindset at the graduate school level, can help bridge the gap. A thorough investigation of domestic and international business models for commercializing AMP technologies was carried out and distilled in the form of the Business Model Canvas developed by Alexander Osterwalder that can be used as a roadmap for commercialization efforts. Using the QCM-D a relationship between both spacer length and peptide surface density and the antimicrobial activity of tethered C-CHY1 was determined. A business plan was developed in order to increase the impact of this and other AMP based work. This work provides a roadmap for future researchers to quickly develop and commercial novel AMP based coating technology.
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When the investors choose : Analysis of business models within the Swedish video game industryKnudsen, Kasper, Söderström, Vilhelm January 2021 (has links)
Many Swedish video game companies have in recent years been very successful in terms of share price development. Why is it like that? With the purpose to gain an increased understanding of the investor's choice, we here examine which business models are used in the Swedish video game industry. More specifically, we try to identify what similarities do the business models in the successful companies share and what similarities do the non-performing companies share. The analytical framework used is based on Business Model Canvas adapted to the video game industry. We use a qualitative approach with case studies of 10 listed Swedish video gaming companies, five successful and five non-performing, in terms of share price development. The data collected is from secondary sources, mainly the companies' annual reports, fitting the investors narrative with the assumption that secondary data is generally what influences the stock price.In general, the results suggest that similarities between business models among the successful companies largely coincide with similarities between the non-performing companies, which makes the information less valuable for understanding investors' choices. Nevertheless, one unique similarity among successful companies applies to that they in general have broad gaming portfolios that target several unrelated customer segments, i.e. a diversified market. The non-performing companies instead mainly target a niche market. Another unique similarity among successful companies’ business models concerns their use of acquisition strategies. In the non-performing companies' business models, acquisition strategies are largely lacking.
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Bringing together engineering and entrepreneurship: understanding the role of tethered C-CHY1 in the fight against antimicrobial resistanceAlexander, Todd E 11 July 2019 (has links)
Healthcare associated infections (HAIs) cost the US healthcare system over $45 billion to treat and cause millions of deaths annually. A large subset of HAIs are associated with medical devices that are meant to improve and save lives. Infected devices are treated using traditional antibiotics, contributing to development of antibiotic resistance. Antibiotic resistance is expected to cost $100 trillion and kill more people a year than cancer by 2050; thus, new alternative antimicrobials for the treatment of device-associated HAIs are critically needed. Antimicrobial peptides (AMPs), such as 26 amino-acid (aa), marine-derived Chrysophsin-1 (CHY1), are poised to reduce HAIs due to their broad antimicrobial activity and unique mechanisms of action that do not promote bacterial resistance. AMPs are short (12-50aa), positively charged (+2-+9) proteins found in the innate immune systems of many different species. Their high separation of hydrophilic and hydrophobic residues leads to many unique mechanisms derived from many unique secondary and tertiary structures that are not yet well understood. Despite the discovery of over 2000 natural AMPs and many more synthetically designed AMPs, none have been successfully commercialized for healthcare applications due to challenges surrounding cytotoxicity, short in vivo half-life (degradation), high costs of production and effectiveness in physiological environments (such as those with high-salt). Several strategies have been investigated to overcome these challenges, for example, truncation of cytotoxic sequences or D-amino acid substitution to improve AMP toxicity and stability; however, many of these strategies can reduce antimicrobial effectiveness. A unique strategy of increasing stability, reducing cytotoxicity, and maintaining antimicrobial activity that is relevant for medical devices is the covalent tethering (binding) of AMPs via a flexible tethering molecule to the surface. However, the effect of tethering parameters on resulting AMP mechanisms and activity is still widely debated. AMP activity can vary widely by utilizing different tethering strategies, which include additional variables such as: (1) peptide choice and properties (such as native mechanism, concentration, charge, and structure), (2) tether choice and properties (such as chemical composition, length, charge, surface density, and flexibility), and (3) testing conditions (such as temperature, solvent composition and substrate type). Some studies suggest that AMP performance may be tether-dependent, for example some AMPs require longer tethers while others do not and some need a flexible tether. Thus, models for predicting successful tethering strategies for different AMP properties, which currently do not exist, must be developed. Further, complicated and often destructive techniques, such as XPS and SEM, are typically implemented to study the relationship of all these parameters vs. antimicrobial activity, which are labor-intensive and limited in scope. Predictive models guiding tether strategy need to be constructed, but also new techniques to study tethering be developed. If these technical milestones are achieved they can serve as a predicate for commercial implementation of a host of new therapies targeted at reducing device-associated HAIs. The overall goal of this thesis was to study the relationship between antimicrobial activity of tethered C-CHY1 examining both spacer length and peptide surface density and the development of a feasible clinical business case for tethered AMPs. To achieve this goal, a traditional entrepreneurial approach was taken in which a minimally-viable product was first designed and business case analyzed, followed by studies to better optimize and understand the underlying structure-mechanism relationships. CHY1 with a C-terminus cysteine to allow for surface-binding (C-CHY1) was tethered onto a silicon dioxide surface via a flexible poly(ethylene glycol) (PEG) tether, and then both surface binding behavior and antimicrobial success of C-CHY1 were examined as a function of tether properties and reaction conditions. For these studies, quartz-crystal microbalance with dissipation (QCM-D) was the primary technique, a real-time, non-destructive flow method that was then coupled with downstream characterization techniques: fluorescent microscopy and contact angle measurements. In parallel a deep dive into domestic and international business models for commercializing AMP technologies. Specifically, tether length and surface density effects on C-CHY1 mechanisms were studied, followed by the effect of temperature, type of microbe, and salt concentration on the antimicrobial mechanisms of tethered C-CHY1. QCM-D was used to measure binding of C-CHY1 via three different length tethers, PEG molecular weight (MW) 866, 2000 and 7500, followed by microscopy to measure antimicrobial effectiveness against two model microbes Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). Modeling of QCM-D data allowed for surface density and thickness to be calculated and related to C-CHY1 antimicrobial activity. PEG 7500 allowed proper C-CHY1 orientation and mobility, allowing for its native pore-forming mechanism and highest activity while PEG 866 tethers led to denser grafting and an effective, yet non-native ion displacement mechanism. The QCM-D was used to characterize the effect of salt concentration and temperature reaction conditions on the grafting density of C-CHY1 tethered via PEG 866 and PEG 7500, which was then related to antimicrobial activity. For PEG MW 866, neither temperature nor salt concentration increases significantly altered the grafting density of C-CHY1 while for PEG 7500 increasing temperature allowed for significantly increased grafting density. C-CHY1 density had no significant effect on antimicrobial activity against either microbe. Temperature of bacterial incubation did demonstrate microbe-specific changes in C-CHY1 antimicrobial activity. These results demonstrated that small changes in reaction conditions can drastically change membrane selectivity of C-CHY1. An in-depth investigation of the effects of bacterial membrane composition and temperature on soluble C-CHY1 mechanism was implemented to better understand the molecular membrane- and temperature-dependent selectivity and structure-function of C-CHY1. Supported lipid bilayers (SLBs) formed in QCM-D can be used as model membranes to elucidate AMP action mechanisms against membranes of different compositions. Two and three component SLBs representative of Gram-negative phosphatidylethanolamine (PE) and phosphatidyglycerol acid (PG) with and without charged lipopolysaccharide, LPS and Gram-positive bacteria phosphatidylcholine (PC) and PG with and without charged lipoteichoic acid, (LTA) were formed at both 23°C and 37°C. C-CHY1 at 5 µM was exposed to the different membranes and mechanistic surface action was studied. The membranes formed highly different baseline responses in QCM-D, indicative of vastly different membrane structures, thicknesses and deposition behaviors on SiO2, warranting future studies. Further, significant effects of LTA incorporation were observed in both peptide interaction and deposition. There were measurable effects of temperature on membrane formation as well as peptide interaction kinetics and even mode of interaction. Lastly, business models for the commercialization of novel medical device technologies such as surface-tethered C-CHY1 were investigated. While this technology has the potential to solve many unmet needs, there must a commercialization plan implemented in order to have an impact. There is a clear disconnect between technology development in academia and technology commercialization in industry that must be connected. Development of an entrepreneurial mindset at the graduate school level, can help bridge the gap. A thorough investigation of domestic and international business models for commercializing AMP technologies was carried out and distilled in the form of the Business Model Canvas developed by Alexander Osterwalder that can be used as a roadmap for commercialization efforts. Using the QCM-D a relationship between both spacer length and peptide surface density and the antimicrobial activity of tethered C-CHY1 was determined. A business plan was developed in order to increase the impact of this and other AMP based work. This work provides a roadmap for future researchers to quickly develop and commercial novel AMP based coating technology.
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