Bioprinting is one of the most promising technologies for future healthcare as it may benefit the repairing of wounds and injuries, disease modeling and development, transplantation of organs and reduce animal testing. This thesis aim to investigate this industry further, as there is no excessive literature on how to handle the innovation in regards to entrepreneurial and biotechnological knowledge. Hence, a research gap can be spotted and the purpose of the conducted research questions should contribute to this gap. In order to fully understand the bioprinting industry, an outline of the technology is made as part of the research. In addition to this, secondary data for patents, market valuation and annual growth rates are collected to support arguments from previous literature. Also, interviews are conducted to gather specific knowledge. As a result, bioprinting may be presented as a disruptive innovation in an uncertain market, which places certain demands on companies to act more in line with the complexity of the technology. Such companies must think more strategically and design more complex and long-term strategies. The patent data shows that there has been a decline in the technological development as patent applications have decreased significantly. Even though the technology (regarding the patents) has started to slowly decline, there is still hope for some technological improvements to come. It can be concluded that developments in bioink, scaffolds, expansion of cells and diffusion is expected, and that the use of bioprinting is increasing and will most likely continue to do so.

[pt] A tecnologia de bioimpressão 3D se tornou um importante recurso em pesquisas médicas no campo da engenharia de tecidos. Entretanto, apesar de essa tecnologia possuir grande convergência e demanda de competências do Design, o profissional designer ainda se encontra distante de tais trabalhos. Esta tese promove a investigação do papel que o Design pode desempenhar em pesquisas envolvendo o uso da bioimpressão 3D. A partir da revisão bibliográfica inicial e da compreensão acerca dos temas da engenharia de tecidos e de biomateriais, foram estabelecidas parcerias visando à execução de uma série de experimentos práticos. A partir da construção de uma bioimpressora desktop e posterior aquisição de uma bioimpressora profissional, foram realizados testes de configuração, calibragem e impressão de diferentes materiais viscosos, para uma melhor compreensão do processo de impressão dos biomateriais. Em parceria com o doutor Ronaldo Andrade, paralelamente se buscou solucionar a questão de simulação prática em treinamentos médicos, visando gerar modelos físicos semelhantes aos tecidos vivos. Por meio de uma parceria com o Grupo de Estudos do Fígado/UFRJ, e com o laboratório do Programa de Engenharia Nuclear, da COPPE/UFRJ, utilizou-se a microtomografia para gerar modelos tridimensionais virtuais que serviram de base para um software de visualização e para a impressão 3D de um fígado de rato. Da parceria com as pesquisadoras Sara Gemini e Jéssica Dornelas, foi possível realizar a impressão de construtos com esferóides celulares e a posterior análise via microscopia. Em nova rodada de experimentos, a biotinta desenvolvida foi aperfeiçoada e testada em diferentes formulações. Além de buscar avanços nos campos investigados, a presente tese buscar mostrar o papel interdisciplinar do Design e seu potencial agregador em pesquisas na área da Ciências Médicas e Biológicas, fugindo do lugar-comum em que o profissional muitas vezes é colocado. / [en] 3D bioprinting technology has become an important resource in medical research, in the field of tissue engineering. However, although this technology has great convergence and demand for skills that Design has, the designer is far from such works. Thisthesis promotesthe investigation of the role that Design can play in researches on the use of 3D bioprinting. From the preliminary bibliographic review and understanding of tissue engineering and biomaterials topics, partnerships were formed in order to develop a series of practical experiments. From the construction of a desktop bioprinter and subsequent acquisition of a professional bioprinter, configuration, calibration and printing tests of different viscous materials were carried out for a better understanding of the printing process of biomaterials. In partnership with Dr. Ronaldo Andrade, an attempt was also made to solve the issue of practical simulation in medical training, with a view to generating physical models similar to living tissue. Through a partnership with the Grupo de Estudos do Fígado/UFRJ, and the laboratory of the Nuclear Engineering Program at COPPE/UFRJ, microtomography was used to generate virtual three-dimensional models that served as the basis for a software for visualization and 3D printing of a mouse liver. In partnership with researchers Sara Gemini and Jéssica Dornelas, it was possible to print constructs with cellular spheroids and subsequently analyze them via microscopy. In a new round of experiments, the developed bioink was improved and tested in different formulations. In addition to seeking advances in the investigated fields, this thesis seeks to show the interdisciplinary role of Design and its aggregating potential in research in the Medical and Biological Sciences areas, escaping the commonplace in which the professional is often placed.

Atualmente, a única alternativa viável para pacientes que possuem um quadro de doença hepática em estágio final é o transplante total ou parcial de fígado. Devido à crescente defasagem entre doadores disponíveis e pacientes em fila de espera, o desenvolvimento de abordagens de engenharia tecidual hepática (ETH) se tornou uma necessidade crescente. As células pluripotentes induzidas (iPS) são uma atraente alternativa para servirem como fonte celular para aplicações de engenharia tecidual por serem capazes de produzir todos os fenótipos celulares. Dentre as principais abordagens de EHT podemos citar as técnicas de bioimpressão 3D, organóides hepáticos e descelularização/recelularização. Este trabalho buscou avaliar a utilização de células iPS no desenvolvimento das três tecnologias descritas. Visando avaliar como imprimir um tecido hepático funcional com células iPS, testamos a impressão com hepatócitos dispersos em células únicas em comparação com a impressão de esferóiedes hepáticos. Os esferóides hepáticos mostraram maior viabilidade e funcionalidade hepática por preservarem o fenótipo epitelial ao longo do tempo. A composição de células não parenquimáticas derivadas de iPS ou células primárias para a formação de organóides hepáticos foi testada neste trabalho. Os resultados indicam que, utilizando células mesenquimais primárias e endoteliais derivadas de iPS, obtém-se uma maturação hepatica mais eficiênte devido a inibição das vias de sinalização TGF-β? e modulação da via Wnt. A recelularização do tecido aórtico descelularizado de ratos com células derivadas de iPS mostrou ser capaz de prover função hepática em cultura assistida por biorreator, porém os resultados indicam a necessidade de aprimoramento do protocolo de recelularização. Este trabalho comprovou a viabilidade da aplicação de células iPS nas abordagens EHT testadas e contribuiu para o desenvolvimento de alternativas terapêuticas viáveis para pacientes em fila de espera de transplante hepático / Currently, the only feasible alternative for patients with end-stage liver disease is total or partial liver transplantation. Due to the growing gap between available donors and patients in waiting list, the development new tissue engineering technologies have become a growing need. Induced pluripotent cells (iPS) are an attractive alternative to serve as cell source for tissue engineering applications due to their ability to differentiate into all cellular phenotypes. Among the main liver tissue engineering technologies, 3D bioprinting, hepatic organoids and decellularization/recellularization of biological matrixes have generated much expectation. Thus, this work aimed to evaluate the use of iPS cells in the development of the aforementioned technologies. In order to evaluate how to bioprint a functional liver tissue using iPS-derived cells, we tested the effect of printing a single cell dispersion of hepatocytes versus printing hepatic spheroids. Hepatic spheroids showed greater viability and liver function, due to preserved epithelial phenotype over time. The composition of non-parenchymal cells using iPS-derived cells or primary adult cells for hepatic organoid formation was tested. The results indicated that, using primary mesenchymal cells and iPS-derived endothelial cells, we obtained a more efficient hepatic maturation due to the inhibition of TGF-β? and modulation Wnt signaling pathway. Recellularization of rat aortic decellularized scaffold with iPS-derived cells displayed hepatic function over time in a bioreactor-assisted culture, but the results indicate the need for improvements in the recellularization protocol. In conclusion, this work demonstrated the feasibility of use of iPS-derived cells for liver tissue engineering approaches and contributed to the development of the investigated technologies in order to generate future therapeutic alternatives for patients in waiting list for liver transplantation

Tissue engineering (TE) uses a combination of biomaterial scaffolds, cells, and drug delivery systems (DDS) to create tissues that resemble the human physiology. Such engineered tissues could be used to treat, repair, replace, and augment damaged tissues or organs, for disease modeling, and drug screening purposes. This work describes the development and use of novel strategies for engineering neural tissue using a combination of drug delivery systems (DDS), human induced pluripotent stem cells (hiPSCs), and bioprinting technologies for the generation of a drug screening tool to be used in the process of drug discovery and development. The DDS consisted of purmorphamine (puro) loaded microspheres that were fabricated using an oil-in-water single emulsion with 84% encapsulation efficiency and showed the slow release of puro for up to 46 days in vitro. Puro and retinoic acid (RA)-loaded microspheres were combined with hiPSCs-derived neural aggregates (NAs) that differentiated into neural tissues expressing βT-III and showed increased neural extension. hiPCS-derived neural progenitor cells (NPCs) were bioprinted on a layer-by-layer using a fibrin based-bioink and extrusion based- bioprinting. The bioprinted structures showed >81% cellular viability after 7 days of culture in vitro and the expression of the mature motor neuron (MN) markers HB9 and CHAT. Lastly, hiPCS-derived NPCs were bioprinted in combination with puro and RA-loaded microspheres and cultured for 45 days in vitro. The microspheres slowly released the drug and after 30 and 45 days the tissues contained mature neurons, astrocytes and oligodendrocytes expressing CHAT, GFAP, and O4, respectively. Changes in membrane potential indicated tissue responsiveness to different types of treatments such as acetylcholine and gamma-aminobutyric acid (GABA). In the future the bioprinted tissues could contain localized regions of varied drug releasing microspheres using a concentration gradient to promote differentiation into specific cell types in order to create more complex tissues. Moreover, these tissues will benefit from the presence of a neurovascular unit (NVU). Upon validation, the engineered tissues could be used as preclinical tools to test potential drugs and be used for personalized medicine by using patient specific hiPSCs. / Graduate / 2020-11-19

No description available.

This thesis examines the critical factors shaping early-stage business model development. As a result, this paper provides insights and recommendations for the effective commercialization of innovations. The early-stage business model development process is notoriously complex and ambiguous, yet a limited amount if empirical studies have been conducted in this crucial phase. To address this research gap, an action research approach is employed to document learnings and challenges through an empirical case study into the early-stage business model development for a novel bioprinting technology. The study leverages existing literature to define specific actions and utilizes reflective analysis to gain comprehensive understanding of the factors shaping the process. Through this approach, important new lessons are uncovered for facilitators, highlighting both the facilitating role of tools and methods, as well as their limitations in enhancing the cognitive processes of understanding customer value, how to create value, and how to capture it efficiently. The research findings demonstrate the the business model development and innovation processes are iterative and complex, as well as heavily reliant on engagement and resource allocation. Furthermore, newfound theoretical considerations of commitment, organizational capabilities, and risk appetite arecrucial for the successful realizability of business models. Based on these findings, recommendations of future business model development in similar contexts are presented. These include the importance of achieving a common understanding among stakeholders, a thorough understanding of customer value, a thoughtful ideation process combining convergent and divergent thinking, and a comprehensive assessment of commitment and tolerance for ambiguity. This these contributes to the exisiting body of literature by holistically shedding light on the early-stage business model development process through documented action and by providing practical insights for practitioners and stakeholders involved in innovation commercialization. / Denna uppsats undersöker de kritiska faktorer som formar utvecklingen av affärsmodeller i tidiga skeden samt bidrar med insikter och rekommendationer för effektiv kommersialisering av innovationer. Processen för utveckling av affärsmodeller i tidiga skeden är känd för sin komplexitet och tvetydighet, men det finns få empiriska studier av denna avgörande fas. För att fylla detta forskningsgap används en aktionsforskningsansats för att dokumentera lärdomar och utmaningar genom en empirisk fallstudie på affärsmodellsutveckling i ett tidigt stadie för en ny bioprintingteknik. Studien utnyttjar befintlig litteratur för att definiera specifika åtgärder och använder reflekterande analys för att skapa en omfattande förståelse för de faktorer som formar processen. Genom detta tillvägagångssätt kan viktiga nya lärdomar dras kring facilitatorer, vilket belyser både verktygens och metodernas underlättande roll och deras begränsningar när det gäller att förbättra den kognitivaprocessen för att förstå kundvärde, hur man skapar och fångar detta värde på ett effektivt sätt. Forskningsresultaten visar att innovationsprocessen för affärsmodeller är iterativ, komplex och starkt beroende av engagemang och resursallokering. Dessutom är nya funna teoretiska överväganden om engagemang, organisatorisk kapacitet och riskaptit avgörande för en framgångsrik realisering av affärsmodeller. Baserat på dessa resultat presenteras rekommendationer för framtida utveckling av affärsmodeller i liknande kontexter. Dessa rekommendationer inkluderar vikten av att uppnå en samsyn bland intressenterna, en grundlig förståelse för kundvärdet, en genomtänkt idéprocess som kombinerar konvergent och divergent tänkande, samt en omfattande bedömning av engagemang och tolerans för ambiguitet. Denna uppsats bidrar till den befintliga kunskapen genom att holistiskt belysa utvecklingsprocessen för affärsmodeller genom dokumenterad handling i ett tidigt skede samt genom att ge praktiska insikter för utövare och intressenter som är involverade i kommersialisering av innovationer.

Les maladies cardiovasculaires sont une des causes de mortalités les plus élevées mondialement. Parmi celles-ci, on retrouve l’infarctus du myocarde, qui n’a pour traitement que la transplantation cardiaque. Or, dû à la faible quantité de donneur, une solution alternative est recherchée. De ce fait, l’ingénierie tissulaire permet le développement de tissus et d’implants thérapeutiques tels les patchs cardiaques, qui peuvent être bioimprimés. Or, une des limitations actuelles de l’utilisation d’une telle stratégie est la vascularisation de tissu bioimprimés. Dans cette étude, la bioimpression 3D a été utilisée afin de bioimprimer des patchs perfusables de gélatine méthacrylate (GelMA) à utiliser potentiellement pour le tissu cardiaque. Il a été possible de développer une bioencre pouvant être utilisée pour une application dans le tissu cardiaque, d’évaluer l’imprimabilité de l’encre et de bioimprimer de patchs standards et perfusables. Pour ce faire, GelMA a été synthétisé et les propriétés mécaniques ont été évaluées pour finalement sélectionner une encre de 10 % GelMA, ayant un module de Young approprié pour le tissu cardiaque, de 23,7±5,1 kPa. Par la suite, les processus d’impression, standard et coaxial, de patchs standards et perfusables ont pu être optimisés. Finalement, des patchs perfusables de GelMA 10% et gélatine 2% ont pu être imprimés avec une viabilité cellulaire élevée, jusqu’à 79,7±8,7 % et 83,5±5,7 % obtenue aux jours 1 et 7 de culture respectivement, avec des fibroblastes 3T3. La présence de canaux vides et la perfusabilité des patchs démontrent le potentiel de cette méthode pour éventuellement bioimprimer des patchs cardiaques vascularisés épais. / Cardiovascular diseases are a leading cause of death worldwide. Myocardial infarction captures a significant segment of this population, and the end-stage myocardial infarction can only be treated by heart transplantation. However, due to the scarcity donors, tissue engineering has been considered as an alternative solution. Tissue engineering allows the development of tissues and therapeutic implants such as cardiac patches. However, one of the main hurdles in the use of such a strategy is the vascularization of bioprinted tissue. In this study, 3D bioprinting was used to bioprint perfusable gelatin methacrylate (GelMA) patches for a potential use in cardiac tissue. This work consists in the development of a bioink that can be used for the cardiac tissue, the evaluation of the printability of the ink, and the final bioprinting of standard and perfusable patches. For this purpose, GelMA was synthesized and a final concentration of 10 % was selected as it showed an appropriate Young's modulus for cardiac tissue, of 23.7±5.1 kPa, while maintaining high biocompatibility. Subsequently, the printing process of standard and perfusable patches could be optimized with the use of GelMA and gelatin inks. Finally, 10% GelMA and 2% gelatin vascularized patches could be printed with high cell viability, of up to 79,7±8,7 % and 83,5±5,7 % on days 1 and 7 of culture respectively for 3T3 fibroblasts. Additionally, the presence of hollow channels of the perfusable patches demonstrates the potential of this method to be eventually applied to the bioprinting of thick vascularized cardiac patches.