35,747 research outputs found

    Natural based eumelanin nanoparticles functionalization and preliminary evaluation as carrier for gentamicin

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    Purpose of the work was to modified natural based eumelanin nanoparticles surface by dopamine selfpolymerization (FEUNp), facilitating conjugation through polydopamine bioactive functional groups and improving nanoparticle surface hydrophilicity. SEM, TEM, and AFM characterization confirmed FEUNp spherical shape (230.04 ± 8.25 nm) and their polydopamine coating. Individual indole or indoline structure spectrum at 1600 cm−1 and C:N mass 9.08 was highlighted by FTIR and XPS analysis respectively. Quartzcrystal microbalance with dissipation monitoring (QCM-D) and thermal gravimetric analysis (TGA) showed successful polydopamine adsorption to eumelanin nanoparticles surface, a weight ratio of eumelanin nanoparticles/dopamine of 1/2.46 in the wet state and 1/0.20 in the dry state; the −36.60 ± 0.45 mV negatively surface charges confirms the presence of PD covering. FEUNp were loaded with gentamicin sulfate, for application in infectious diseases therapies, such as osteomyelitis. Nanoparticles drug entrapment efficiency was 32.42 ± 3.21%, and ζ-potential close to neutrality (−1.84 ± 0.58 mV). FEUNp-GS antimicrobial effect was tested on Staphylococcus aureus and Escherichia coli showing gentamicin 24 h sustained release from FEUNp-GS. IC50 and IC90 were 110.60 μg/mL and 216.39 μg/mL against S. aureus, and 54.13 μg/mL and 101.25 μg/mL against E. coli. The results are promising for FEUNp-GS as delivery system potentially useful diverse administration routes.The authors acknowledge the work was supported by the European Union (Horizon 2020) funded project FoReCaST (n° 668983), FEDER (n° 007038), through the Competitiveness Factors Operational Programme (COMPETE), and by National funds, through the Foundation for Science and Technology (FCT), under the scope of the Project POCI-01-0145-FEDER-007038. Alexandra G. Fraga was supported by the FCT fellowship SFRH/BPD/ 112903/2015. Rui R. Costa acknowledges the financial support from Fundação para a Ciência e Tecnologia (Grant SFRH/BPD/95446/2013), “Fundo Social Europeu” (FSE), and “Programa Operacional de Potencial Humano” (POPH). The FCT fellowship distinction attributed to Vitor M. Correlo under the Investigator FCT program (IF/01214/2014) is also greatly acknowledged. We also thank Khon Kaen University, Thailand for financial support to Pathomthat Srisuk.info:eu-repo/semantics/publishedVersio

    The crosstalk between tissue engineering and pharmaceutical biotechnology: Recent advances and future directions

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    Tissue-engineered constructs made of biotechnology-derived materials have been preferred due to their chemical and physical composition, which offers both high versatility and a support to enclose/incorporate relevant signaling molecules and/or genes known to therapeutically induce tissue repair. Herein, a critical overview of the impact of different biotechnology-derived materials, scaffolds, and recombinant signaling molecules over the behavior of cells, another element of tissue engineered constructs, as well its regulatory role in tissue regeneration and disease progression is given. Additionally, these tissue-engineered constructs evolved to three-dimensional (3D) tissue-like models that, as an advancement of two-dimensional standard culture methods, are expected to be a valuable tool in the field of drug discovery and pharmaceutical research. Despite the improved design and conception of current proposed 3D tissue-like models, advanced control systems to enable and accelerate streamlining and automation of the numerous labor-intensive steps intrinsic to the development of tissue-engineered constructs are still to be achieved. In this sense, this review intends to present the biotechnology-derived materials that are being explored in the field of tissue engineering to generate 3D tissue-analogues and briefly highlight their foremost breakthroughs in tissue regeneration and drug discovery. It also aims to reinforce that the crosstalk between tissue engineering and pharmaceutical biotechnology has been fostering the outcomes of tissue engineering approaches through the use of biotechnology-derived signaling molecules. Gene delivery/therapy is also discussed as a forefront area that represents another cross point between tissue engineering and pharmaceutical biotechnology, in which nucleic acids can be considered a â super pharmaceuticalâ to drive biological responses, including tissue regeneration. We would like to acknowledge "RL1 - ABMR - NORTE- 01-0124-FEDER-000020" co-financed by North Portugal Regional Operational Programme (ON. 2 - O Novo Norte), under the National Strategic Reference Framework (NSRF), through the European Regional Development Fund (ERDF), and to BIOTERFACE (M-ERA.NET/0003/2012). The authors would also like to thank Mariana Cerqueira, PhD, Alessandra Zonari, PhD, and Lucilia da Silva, MSc, for the provided images

    Development of an injectable PHBV microparticles-GG hydrogel hybrid system for regenerative medicine

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    Uncontrollable displacements that greatly affect the concentration of active agents at the target tissues are among a major limitation of the use of microparticulate drug delivery systems (DDS). Under this context a biphasic injectable DDS combining poly(hydroxybutyrate-co-hydroxyvalerate) (PHBV) microparticles (MPs) and a gellan gum (GG) injectable hydrogel is herein proposed for the localized delivery and long-term retention of MPs carrying hydrophilic and hydrophobic model active agents. A double emulsion-solvent evaporation method was adopted to develop the PHBV MPs, carrying bovine serum albumin (BSA) or dexamethasone (Dex) as hydrophilic and hydrophobic active agents’ models, respectively. Moreover, this method was modified, together with the properties of the hydrogel to tailor the delivery profile of the active agents. Variations of the composition of the organic phase during the process allowed tuning surface topography, particle size distribution and core porosity of the PHBV MPs and, thus, the in vitro release profile of Dex but not of BSA. Besides, after embedding hydrogels of higher GG concentration led to a slower and more sustained release of both active agents, independently of the processing conditions of the microparticulate system.The authors would like to acknowledge the Project RL1 - ABMR - NORTE-01-0124-FEDER-000016 co-financed by North Portugal Regional Operational Programme (ON.2 - O Novo Norte), under the National Strategic Reference Framework (NSRF), through the European Regional Development Fund (ERDF). This work was partially supported by European Research Council grant agreement ERC-2012-ADG 20120216-321266 for project ComplexiTE

    Informetrics on M. N. Srinivas

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    M. N. Srinivas, the well known sociologist is widely recognised as architect of modern Indian sociology and social anthropology. His publications have been analysed by year, domain, authorship pattern, channels of communication used. Keywords, etc. The results indicate that the papers published by him are of a nature that qualify him to be a 'role model' for the younger generations to emulate. By the end of 1995, Srinivas had to his credit 144 papers which, included 33 broad papers in sociology and anthropology; 18 papers in social change; 28 papers in village studies; 12 papers on religion; 17 papers on caste and 36 papers of general popular interest. The periods 1958-61 and 1974-77, when Srinivas was 38-41 and 58-61 years old. were his most productive periods with highest publication activity

    Anti-cancer drug validation: the contribution of tissue engineered models

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    Abstract Drug toxicity frequently goes concealed until clinical trials stage, which is the most challenging, dangerous and expensive stage of drug development. Both the cultures of cancer cells in traditional 2D assays and animal studies have limitations that cannot ever be unraveled by improvements in drug-testing protocols. A new generation of bioengineered tumors is now emerging in response to these limitations, with potential to transform drug screening by providing predictive models of tumors within their tissue context, for studies of drug safety and efficacy. Considering the NCI60, a panel of 60 cancer cell lines representative of 9 different cancer types: leukemia, lung, colorectal, central nervous system (CNS), melanoma, ovarian, renal, prostate and breast, we propose to review current Bstate of art^ on the 9 cancer types specifically addressing the 3D tissue models that have been developed and used in drug discovery processes as an alternative to complement their studyThis article is a result of the project FROnTHERA (NORTE-01-0145-FEDER-000023), supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). This article was also supported by the EU Framework Programme for Research and Innovation HORIZON 2020 (H2020) under grant agreement n° 668983 — FoReCaST. FCT distinction attributed to Joaquim M. Oliveira (IF/00423/2012) and Vitor M. Correlo (IF/01214/2014) under the Investigator FCT program is also greatly acknowledged.info:eu-repo/semantics/publishedVersio

    Melt processing of chitosan-based fibers and fiber-mesh scaffolds for the engineering of connective tissues

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    We report the production of chitosan-based fibers and chitosan fiber-mesh structures by melt processing (solvent-free) to be used as tissue-engineering scaffolds. The melt-based approach used to produce the scaffolds does not change their main characteristics, including the surface roughness and microporosity. The porosity, pore size, interconnectivity and mechanical performance of the scaffolds are all within the range required for various tissue-engineering applications. Biological assessments are performed in direct-contact assays. Cells are able to colonize the scaffold, including the inner porous structure. The cells show high indices of viability in all of the scaffold types.Vitor M. Correlo and Ana Costa-Pinto would like to acknowledge the Portuguese Foundation for Science and Technology (FCT) for their grants: SFRH/BD/22455/2005 and SFRH/24735/2005, respectively. M. Bhattacharya would like to thank FLAD (Fundacao Luso-Americana para o Desenvolvimento) for generous support of sabbatical funds towards this research

    Estratégias de engenharia de tecidos para o tratamento de lesões do músculo esquelético

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    Tese de doutoramento em Engenharia de Tecidos, Medicina Regenerativa e Células EstaminaisAté à data, não existem tratamentos eficazes para lesões musculares. Atualmente, os tratamentos existents para lesões musculares são limitados a cuidados paliativos ou cirurgias. Portanto, há uma necessidade premente de encontrar um tratamento eficaz para as lesões musculares esqueléticas. O primeiro objectivo desta tese foi investigar o potencial de células estaminais derivadas do tecido adiposo humano (hASCs) para a regeneração do músculo. Deste modo, lesões musculares em murganhos foram tratadas com hidrogéis esponjosos (SLH) à base de goma gelana (GG) e biofuncionalizados com RGD contendo hASCs. Esta estratégia demonstrarou ser uma abordagem confiável, dado que restabeleceu a rede vascular e os filamentos neurais, assim como promoveu a miogénese. O segundo objectivo baseou se na investigação do potencial de análogos do músculo esquelético para terapias de substituição ou para modelo de músculo esquelético para estudar a fisiologia do músculo esquelético ou para triagem de medicamentos. Portanto, hidrogéis à base de goma gelana foram biofuncionalizados com oligopeptídeos inspirados em laminina (isto é, CIKVAVS (V), KNRLTIELEVRTC (T), RKRLQVQLSIRTC (Q) e cRGD) e preparados com diferentes conteúdos polimérico. Miócitos foram adicionados no topo ou dentro dos hidrogéis e o seu comportamento ao longo do tempo. A adesão celular foi favorecida em hidrogéis com rigidez semelhante à do tecido muscular nativo (ou seja, 5-20 kPa). Além disso, os miócitos foram capazes de aderir, crescer, diferenciar e alinhar sobre hidrogéis à base de Q micropadronizados. No entanto, apesar de os miócitos aderirem, proliferarem e alinharem após bio impressão dentro das diferentes formulações de hidrogel, a diferenciação só foi alcançada quando impressos em hidrogéis baseados em cRGD. De modo a preparar análogos de músculo inervados, células neuronais foram bio-impressas lado a lado com células do músculo esquelético. Estes análogos demonstraram superior funcionalidade, como foi detectado pela descarga de cálcio e contratilidade. Por fim, o potencial dos miócitos encapsulados em hidrogéis à base de Q foi explorado para tratamento lesões musculares localizadas, por meio de injeção direta in-situ. Após a injeção, este tratamento promoveu uma miogénese, restabelecendo uma rede vascular profunda e filamentos neurais.Ongoing treatment procedures for skeletal muscle injuries are limited to palliative care therapy or surgery in severe cases. The main drawback of these approaches is the absence of functional recovery portrayed with a prolonged recovery scheme that may last months. Hence, there is an urgent need to find an effective treatment for skeletal muscle injuries. In this thesis, we aimed to explore the potential of human adipose-derived stem cells (hASCs) for the regeneration of volumetric muscle loss (VML). To this aim, we used gellan gum (GG)-based spongy-like hydrogels (SLH) biofunctionalized with RGD. hASCs-laden spongy-like hydrogels demonstrated a reliable approach by re-establishing a vascular network, neural filaments and promoting myogenesis. Moreover, we explored the potential of the skeletal muscle-analogue model for drug screening applications, pathophysiological studies, or to be used for in-vivo replacement therapies. Hence, we developed gellan gum-based hydrogels biofunctionalized with laminin-inspired oligopeptides (i.e. CIKVAVS (V), KNRLTIELEVRTC (T), RKRLQVQLSIRTC (Q), and cRGD) with different polymeric contents. Thus, we analyzed the behavior of C2C12 within and on top of these hydrogels. Cell adhesion was favored in hydrogels with compressive modulus close to the native muscular tissue stiffness (i.e. 5-20 kPa). Moreover, C2C12 cells were able to differentiate and align when seeded on top of Q-based micropatterned hydrogels. When encapsulated within the different hydrogel formulations, C2C12 cells were able to adhere, grow and align post-printing. Nevertheless, differentiation was only achieved when cells were bioprinted within cRGD-based hydrogels. Furthermore, innervated constructs were prepared by printing neuronal cells side-by-side to skeletal muscle cells, showing enhanced functionality as detected by calcium discharge and contractility. In the final work, we explored the potential of C2C12 laden in Q-biofunctionalized GG-based hydrogels to treat localized muscle injuries through direct in-situ injection. Post injection, C2C12-laden hydrogels promoted robust myogenesis, re-established a profound vascular network and neural filaments.Fundação para a Ciência e a Tecnologia (FCT

    Natural origin materials for bone tissue engineering – properties, processing and performance

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    Medical advances have increased life expectancy worldwide. At the same time, age-related pathologies have increased. Bone injuries are a burden among the aging population and are associated with significant socioeconomic costs. Thus, there is a need for new and efficient therapies. Advanced tissue engineering-based approaches have focused on the combination of cells, biologically active molecules, and a temporary three-dimensional porous scaffold to repair and regenerate damaged bone tissue. This chapter provides an overview of natural-based polymers and ceramics that are used as scaffolds, with a special focus on their properties, processing methods, and performance in bone tissue engineering applications.F.R. Maia acknowledges Portuguese Foundation for Science and Technology (FCT) for her Postdoc scholarship (SFRH/BPD/117492/2016), ERC-2012-ADG 20120216-321266 (ComplexiTE) and project Hierarchitech, financed by the FCT. J.M. Oliveira thanks FCT for his distinction attributed under the FCT Investigator program (IF/00423/2012 and IF/01285/2015). V.M. Correlo acknowledges Investigator FCT program (IF/01214/2014

    Illuminaçao Apologetica do retrato de Morteçor en que aparecem com mais vivas côres os erros do author do novo Methodo, e seu Apologista ...

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