Chitosan conduits enriched with fibrin-collagen hydrogel with or without adipose-derived mesenchymal stem cells for the repair of 15-mm-long sciatic nerve defect

Hollow conduits of natural or synthetic origins have shown acceptable regeneration results in short nerve gap repair; however, results are still not comparable with the current gold standard technique “autografts”. Hollow conduits do not provide a successful regeneration outcome when it comes to critical nerve gap repair. Enriching the lumen of conduits with different extracellular materials and cells could provide a better biomimicry of the natural nerve regenerating environment and is expected to ameliorate the conduit performance. In this study, we evaluated nerve regeneration in vivo using hollow chitosan conduits or conduits enriched with fibrin-collagen hydrogels alone or with the further addition of adipose-derived mesenchymal stem cells in a 15 mm rat sciatic nerve transection model. Unexpected changes in the hydrogel consistency and structural stability in vivo led to a failure of nerve regeneration after 15 weeks. Nevertheless, the molecular assessment in the early regeneration phase (7, 14, and 28 days) has shown an upregulation of useful regenerative genes in hydrogel enriched conduits compared with the hollow ones. Hydrogels composed of fibrin-collagen were able to upregulate the expression of soluble NRG1, a growth factor that plays an important role in Schwann cell transdifferentiation. The further enrichment with adipose-derived mesenchymal stem cells has led to the upregulation of other important genes such as ErbB2, VEGF-A, BDNF, c-Jun, and ATF3.Spanish "Plan Nacional de Investigacion Cientifica, Desarrollo e Innovacion Tecnologica, Ministerio de Economia y Competitividad (Instituto de Salud Carlos III) FIS PI14-1343 FIS PI17-0393 FIS PI20-0318Fondo Europeo de Desarrollo Regional ERDF-FEDER European UnionPlan Andaluz de Investigacion, Desarrollo e Innovacion (PAIDI2020), Consejeria de Transformacion Economica, Industria, Conocimiento y Universidades, Junta de Andalucia, Espana P18-RT-5059Programa Operativo FEDER Andalucia 2014-2020, Universidad de Granada, Junta de Andalucia, Espana A-CTS-498-UGR18European Commissio

a theranostic toolbox for personalized medicine

Funding Information: This work was supported by an ERC Advanced Grant 787510 4DbioSERS from the European Research Council. C.F.M. acknowledges the National funding by FCT, Foundation for Science and Technology, through an individual research grant (2022.11436.BD). C.G.-A. acknowledges a Juan de la Cierva Incorporación Fellowship from the Spanish Ministry of Science, Innovation and Universities (IJC2019-040827-I). J.C. acknowledge the European Research Council Starting Grant (ERC-StG-2019–848325). Publisher Copyright: © The Author(s) 2024.Due to the severity and high prevalence of cancer, as well as its complex pathological condition, new strategies for cancer treatment and diagnostics are required. As such, it is important to design a toolbox that integrates multiple functions on a single smart platform. Theranostic hydrogels offer an innovative and personalized method to tackle cancer while also considering patient comfort, thereby facilitating future implementation and translation to the clinic. In terms of theranostic systems used in cancer therapy, nanoparticles are widely used as diagnostic and therapeutic tools. Nanoparticles can achieve systemic circulation, evade host defenses, and deliver drugs and signaling agents at the targeted site, to diagnose and treat the disease at a cellular and molecular level. In this context, hydrogel microneedles have a high potential for multifunctional operation in medical devices, while avoiding the complications associated with the systemic delivery of therapeutics. Compared with oral administration and subcutaneous injection, microneedles offer advantages such as better patient compliance, faster onset of action, and improved permeability and efficacy. In addition, they comprise highly biocompatible polymers with excellent degradability and tunable properties. Nanoparticles and microneedles thus offer the possibility to expand the theranostic potential through combined synergistic use of their respective features. We review herein recent advances concerning processing methods and material requirements within the realm of hydrogel microneedles as theranostic platforms, various approaches toward cancer therapy, and the incorporation of nanoparticles for added functionality. Graphical Abstract: (Figure presented.)publishersversionepub_ahead_of_prin

Generation of a novel human dermal substitute functionalized with antibiotic‑loaded nanostructured lipid carriers (NLCs) with antimicrobial properties for tissue engineering

Background: Treatment of patients affected by severe burns is challenging, especially due to the high risk of Pseudomonas infection. In the present work, we have generated a novel model of bioartificial human dermis substitute by tissue engineering to treat infected wounds using fibrin-agarose biomaterials functionalized with nanostructured lipid carriers (NLCs) loaded with two anti-Pseudomonas antibiotics: sodium colistimethate (SCM) and amikacin (AMK). Results: Results show that the novel tissue-like substitutes have strong antibacterial effect on Pseudomonas cultures, directly proportional to the NLC concentration. Free DNA quantification, WST-1 and Caspase 7 immunohistochemical assays in the functionalized dermis substitute demonstrated that neither cell viability nor cell proliferation were affected by functionalization in most study groups. Furthermore, immunohistochemistry for PCNA and KI67 and histochemistry for collagen and proteoglycans revealed that cells proliferated and were metabolically active in the functionalized tissue with no differences with controls. When functionalized tissues were biomechanically characterized, we found that NLCs were able to improve some of the major biomechanical properties of these artificial tissues, although this strongly depended on the type and concentration of NLCs. Conclusions: These results suggest that functionalization of fibrin-agarose human dermal substitutes with antibioticloaded NLCs is able to improve the antibacterial and biomechanical properties of these substitutes with no detectable side effects. This opens the door to future clinical use of functionalized tissues.NanoGSkin project of EuroNanoMed-III (ERA-NET Cofund scheme of the Horizon 2020 Research and Innovation Framework Programme), EUInstituto de Salud Carlos III AC17/00013Centro para el Desarrollo Tecnológico Industrial -CDTI 00108589Spanish GovernmentJunta de Andalucía PE-0395-2019Fundacion Benefica Anticancer San Francisco Javier y Santa Candida, Granada, SpainDepartment of Economic Development and Infrastructure of the Basque Government budget, through the HAZITEK business R + D support program ZE-2017/00014European Union (EU) OTRI.35A-0

Desencanto y disidencia: Estudios sobre la crisis del comunismo en España

El libro reúne los trabajos de nueve especialistas -bajo la coordinación de dos de los autores- acerca de diferentes aspectos de la crisis que afectó al Partido Comunista de España a comienzos de los ochenta, con 1982 como epicentro de un fenómeno autodestructivo cuyas raíces endógenas y exógenas se rastrean bastantes años atrás y cuyas consecuencias se prolongaron hasta la caída del Muro de Berlín, que dio pie a un nuevo fenómeno global de crisis del movimiento comunista. En los distintos capítulos se trata de arrojar perspectivas nuevas, entroncadas con las tendencias más recientes de la historiografía internacional y que van más allá (en síntesis, sin dejar nunca de lado) de la más tradicional historia política. De este modo, se estudia la crisis del comunismo español desde la memoria, la historia de las emociones, la historia desde abajo, la historia cultural o la historia transnacional. La hipótesis fundamental sitúa en los factores endógenos (la quiebra de la tradicional identidad comunista a la luz de la evolución del PCE, principalmente) las motivaciones principales para la crisis del comunismo en España, pero también se dedican tres capítulos a abordar la vertiente exógena de esta crisis (mediante el estudio de la crisis en el contexto internacional y en el marco de relaciones con los soviéticos y los alemanes del Este). Para ello, se recurre a numerosas fuentes archivísticas y hemerográficas nacionales e internacionales, a una amplia bibliografía y a testimonios orales.En conformidad con las condiciones del contrato de edición de "Ediciones Universidad de Valladolid", esta monografía se publicará inicialmente en papel. Transcurrido un periodo de embargo, se difundirá en formato digital y en acceso abierto

Development and experimental validation of a thermoelectric test bench for laboratory lessons

The refrigeration process reduces the temperature of a space or a given volume while the power generation process employs a source of thermal energy to generate electrical power. Because of the importance of these two processes, training of engineers in this area is of great interest. In engineering courses it is normally studied the vapor compression and absorption refrigeration, and power generation systems such as gas turbine and steam turbine. Another type of cooling and generation less studied within the engineering curriculum, having a great interest, it is cooling and thermal generation based on Peltier and Seebeck effects. The theoretical concepts are useful, but students have difculties understanding the physical meaning of their possible applications. Providing students with tools to test and apply the theory in real applications, will lead to a better understanding of the subject. Engineers must have strong theoretical, computational and also experimental skills. A prototype test bench has been built and experimentally validated to perform practical lessons of thermoelectric generation and refrigeration. Using this prototype students learn the most effective way of cooling systems and thermal power generation as well as basic concepts associated with thermoelectricity. It has been proven that students learn the process of data acquisition, and the technology used in thermoelectric devices. These practical lessons are implemented for a 60 people group of students in the development of subject of Thermodynamic including in the Degree in Engineering in Industrial Technologies of Public University of NavarraPeer Reviewe