An anti-interleukin-2 receptor drug attenuates thelper 1 lymphocytes-mediated inflammation in an acute model of endotoxin-induced uveitis

The aim of the present study was to evaluate the anti-inflammatory efficacy of Daclizumab, an anti-interleukin-2 receptor drug, in an experimental uveitis model upon a subcutaneous injection of lipopolysaccharide into Lewis rats, a valuable model for ocular acute inflammatory processes. The integrity of the blood-aqueous barrier was assessed 24 h after endotoxin-induced uveitis by evaluating two parameters: cell count and protein concentration in aqueous humors. The histopathology of all the ocular structures (cornea, lens, sclera, choroid, retina, uvea, and anterior and posterior chambers) was also considered. Enzyme-linked immunosorbent assays of the aqueous humor samples were performed to quantify the levels of the different chemokine and cytokine proteins. Similarly, a biochemical analysis of oxidative stress-related markers was also assessed. The inflammation observed in the anterior chamber of the eyes when Daclizumab was administered with endotoxin was largely prevented since the aqueous humor protein concentration substantially lowered concomitantly with a significant reduction in the uveal and vitreous histopathological grading. Th1 lymphocytes-related cytokines, such as Interleukin-2 and Interferon-c, also significantly reduced with related anti-oxidant systems recovery. Daclizumab treatment in endotoxin-induced uveitis reduced Th1 lymphocytes-related cytokines, such as Interleukin-2 and Interferon gamma, by about 60–70% and presented a preventive role in endotoxin-induced oxidative stress. This antioxidant protective effect of Daclizumab may be related to several of the observed Daclizumab effects in our study, including IL-6 cytokine regulatory properties and a substantial concomitant drop in INFc. Concurrently, Daclizumab treatment triggered a significant reduction in both the uveal histopathological grading and protein concentration in aqueous humors, but not in cellular infiltration

Alginate-Agarose Hydrogels Improve the In Vitro Differentiation of Human Dental Pulp Stem Cells in Chondrocytes. A Histological Study

[EN] Matrix-assisted autologous chondrocyte implantation (MACI) has shown promising results for cartilage repair, combining cultured chondrocytes and hydrogels, including alginate. The ability of chondrocytes for MACI is limited by different factors including donor site morbidity, dedifferentiation, limited lifespan or poor proliferation in vitro. Mesenchymal stem cells could represent an alternative for cartilage regeneration. In this study, we propose a MACI scaffold consisting of a mixed alginate-agarose hydrogel in combination with human dental pulp stem cells (hDPSCs), suitable for cartilage regeneration. Scaffolds were characterized according to their rheological properties, and their histomorphometric and molecular biology results. Agarose significantly improved the biomechanical behavior of the alginate scaffolds. Large scaffolds were manufactured, and a homogeneous distribution of cells was observed within them. Although primary chondrocytes showed a greater capacity for chondrogenic differentiation, hDPSCs cultured in the scaffolds formed large aggregates of cells, acquired a rounded morphology and expressed high amounts of type II collagen and aggrecan. Cells cultured in the scaffolds expressed not only chondral matrix-related genes, but also remodeling proteins and chondrocyte differentiation factors. The degree of differentiation of cells was proportional to the number and size of the cell aggregates that were formed in the hydrogels.This work was funded by the Ministry of Economy and Competitiveness of the Spanish Government (PID2019-106099RB-C42, MM) and by the Generalitat Valenciana, Spain (PROMETEO/2020/069, CC). CIBER-BBN and CIBER-ER are financed by the VI National R&D&I Plan 2008-2011, Iniciativa Ingenio 2010, Consolider Program, CIBER Actions and the Instituto de Salud Carlos III, with assistance of the European Regional Development Fund.Oliver-Ferrándiz, M.; Milián, L.; Sancho-Tello, M.; Martín De Llano, JJ.; Gisbert-Roca, F.; Martínez-Ramos, C.; Carda, C.... (2021). Alginate-Agarose Hydrogels Improve the In Vitro Differentiation of Human Dental Pulp Stem Cells in Chondrocytes. A Histological Study. Biomedicines. 9(7):1-22. https://doi.org/10.3390/biomedicines9070834S1229

Biostable scaffolds of polyacrylate polymers implanted in the articular cartilage induce hyaline-like cartilage regeneration in rabbits

[EN] Purpose: To study the influence of scaffold properties on the organization of ¿in vivo¿ cartilage regeneration. Our hypothesis is that stress transmission to the cells seeded inside the scaffold pores or surrounding it, which is highly dependent on the scaffold properties, determine differentiation of both mesenchymal cells and dedifferentiated autologous chondrocytes. Methods: Four series of porous scaffolds made of different polyacrylate polymers, previously seeded with cultured rabbit chondrocytes or without cells preseeded, were implanted in cartilage defects in rabbits. Subchondral bone was always injured during the surgery in order to allow blood to reach the implantation site and fill scaffold pores. Results: Three months after implant, excellent tissue regeneration was obtained, with a well-organized layer of hyaline cartilage at the condylar surface in most cases of the hydrophobic or slightly hydrophilic series. The most hydrophilic material induced the poorest regeneration. However, few variations were observed between the preseeded and non-preseeded scaffolds. All the materials employed were biocompatible, biostable polymers, therefore, in contrast to other studies, our results are not perturbed by possible effects attributable to material degradation products, or to the loss of scaffold mechanical properties over time due to degradation. Conclusions: Cartilage regeneration mainly depends on the properties of the scaffold, such as stiffness and hydrophility, whereas little differences were observed between preseeded and non-preseeded scaffolds.Supported by the Ministry of Economy and Competitiveness through project No. MAT2013-46467-C4-R, including the FEDER financial support. CIBER-BBN is an initiative funded by the VI National R&D&I Plan 2008-2011, Iniciativa Ingenio 2010, Consolider Program. CIBER Actions are financed by the Instituto de Salud Carlos III with assistance from the European Regional Development Fund.Sancho-Tello, M.; Forriol, F.; Martín De Llano, JJ.; Antolinos Turpín, CM.; Gómez-Tejedor, J.; Gómez Ribelles, JL.; Carda, C. (2017). Biostable scaffolds of polyacrylate polymers implanted in the articular cartilage induce hyaline-like cartilage regeneration in rabbits. The International Journal of Artificial Organs. 40(7):350-357. https://doi.org/10.5301/ijao.5000598S35035740

Design and validation of the questionnaire for the inclusive assessment of the "philosophical potentials" of people with intellectual (dis)abilities based on the "Free Thinking Approach"

El artículo presenta el primer estudio validado de capacidades (entendidas como “potenciales filosóficos”) de personas con (dis)capacidad intelectual o diversidad funcional intelectual. La investigación ha evaluado tres potenciales filosóficos concretos: en primer lugar, los potenciales de pensamiento entendidos como procesos de empoderamiento crítico y no solo como destrezas cognitivas. En estos potenciales, la importancia de las preguntas filosóficas de las personas es un elemento indispensable; en segundo lugar, los potenciales creativos entendidos como procesos de razonamiento divergente o lateral en el cual se tratan de buscar soluciones alternativas a problemas reales o imaginarios; y, en tercer lugar, los potenciales morales entendidos como procesos de toma de decisiones que tenga en cuenta la dimensión ética y emocional de cualquier persona como parte de una comunidad moral y política. Este cuestionario utiliza la metodología denominada “Enfoque Pensamiento Libre” en contextos de desventajas cognitivas, una metodología que se inspira en la “metodología Lipman” y otras metodologías procedentes del campo de la educación emocional y educación en valores. La conclusión a la que hemos llegado es que la validación de este cuestionario supone la confirmación de la importancia del “diálogo filosófico” en los procesos de empoderamiento de las personas con desventajas cognitivas, en este caso, la (dis)capacidad intelectual, para evitar la exclusion o injusticia epistémica de las voces subalternas. Después de las sesiones realizadas durante un curso escolar, las personas con (dis)capacidad realizaron avances significativos en los items analizados en el cuestionario y que aparecen en este artículo. Este cuestionario puede ser implementado en los Centros Ocupacionales o Centros Educativos donde los profesionales de los servicios sociales comunitarios o de la educación formal deseen evaluar las capacidades de las personas a las que tradicionalmente se las ha excluído de estas dimensiones.This article presents the first validated study of capacities (understood as "philosophical potentials") of people with intellectual (dys)ability or intellectual functional diversity. The research carried out aims to assess three specific philosophical potentials: firstly, thinking potentials understood as processes of critical empowerment and not only as cognitive skills, in these potentials, the importance of people's philosophical questions is an indispensable element; secondly, creative potentials understood as processes of divergent or lateral reasoning in which alternative solutions to real or imaginary problems are sought; and thirdly, moral potentials understood as decision-making processes that take into account the ethical and emotional dimension of any person as part of a moral and political community. This questionnaire uses the methodology called "Free Thinking Approach" in contexts of cognitive disadvantage, a methodology that is inspired by the "Lipman methodology" and other methodologies from the field of emotional education and values education. The conclusion we have reached is that the validation of this questionnaire confirms the importance of the "philosophical dialogue" in the processes of empowerment of people with cognitive disadvantages, in this case (dis)intellectual capacity to avoid the exclusion or epistemic injustice of the subaltern voices of our complex societies. After the sessions carried out during a school year, people with disabilities made significant progress in the items analysed in the questionnaire and which appear in this article. This questionnaire can be implemented in Occupational Centres or Educational Centres where professionals of community social services or formal education wish to assess the philosophical potentials of people who have traditionally been excluded from these dimensions

Optimization of a decellularized protocol of porcine tracheas. Long-term effects of cryopreservation. A histological study

[EN] Objective: The aim of this study was to optimize a decellularization protocol in the trachea of Sus scrofa domestica (pig) as well as to study the effects of long-term cryopreservation on the extracellular matrix of decellularized tracheas. Methods: Porcine tracheas were decellularized using Triton X-100, SDC, and SDS alone or in combination. The effect of these detergents on the extracellular matrix characteristics of decellularized porcine tracheas was evaluated at the histological, biomechanical, and biocompatibility level. Morphometric approaches were used to estimate the effect of detergents on the collagen and elastic fibers content as well as on the removal of chondrocytes from decellularized organs. Moreover, the long-term structural, ultrastructural, and biomechanical effect of cryopreservation of decellularized tracheas were also estimated. Results: Two percent SDS was the most effective detergent tested concerning cell removal and preservation of the histological and biomechanical properties of the tracheal wall. However, long-term cryopreservation had no an appreciable effect on the structure, ultrastructure, and biomechanics of decellularized tracheal rings. Conclusion: The results presented here reinforce the use of SDS as a valuable decellularizing agent for porcine tracheas. Furthermore, a cryogenic preservation protocol is described, which has minimal impact on the histological and biomechanical properties of decellularized porcine tracheas.The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by grants MAT2016-76039-C4-2-R (MST) and PID2019-106099RB-C42 (MM) from the Ministry of Economy and Competitiveness of the Spanish Government, by grant PI16-01315 from the ISCIII (Ministerio de Ciencia, Innovacion y Universidades, Spain), and by grant PROMETEO/2020/069 (CC) from the local government of the Comunitat Valenciana (Spain), CIBER-BBN and CIBERER are funded by the VI National R&D&I Plan 2008-2011, Iniciativa Ingenio 2010, Consolider Program, CIBER Actions, and the Instituto de Salud Carlos III, with assistance from the European Regional Development Fund.Milián, L.; Sancho-Tello, M.; Roig-Soriano, J.; Foschini, G.; Martínez-Hernández, NJ.; Más Estellés, J.; Ruiz-Sauri, A.... (2021). Optimization of a decellularized protocol of porcine tracheas. Long-term effects of cryopreservation. A histological study. The International Journal of Artificial Organs. 44(12):998-1012. https://doi.org/10.1177/03913988211008912S9981012441

Outcomes and effect of somatic mutations after erythropoiesis stimulating agents in patients with lower-risk myelodysplastic syndromes

Background: Erythropoiesis stimulating agents (ESAs) are the first-line therapy in patients with lower-risk myelodysplastic syndromes (LR-MDS). Some predictive factors for ESAs response have been identified. Type and number of somatic mutations have been associated with prognosis and response to therapies in MDS patients.Objectives: The objective was to evaluate the outcomes after ESAs in patients with LR-MDS and to address the potential predictive value of somatic mutations in ESAs-treated patients.Design: Multi-center retrospective study of a cohort of 722 patients with LR-MDS included in the SPRESAS (Spanish Registry of Erythropoietic Stimulating Agents Study) study. Retrospective analysis of 65 patients with next generation sequencing (NGS) data from diagnosis.Methods: ESAs' efficacy and safety were evaluated in patients receiving ESAs and best supportive care (BSC). To assess the potential prognostic value of somatic mutations in erythroid response (ER) rate and outcome, NGS was performed in responders and non-responders.Results: ER rate for ESAs-treated patients was 65%. Serum erythropoietin (EPO) level = 3; p = 0.170). The presence of >= 3 mutated genes was also significantly associated with worse OS (hazard ratio, 2.8; p= 0.015), even in responders. A higher cumulative incidence of acute myeloid leukemia progression at 5 years was also observed in patients with >= 3 mutated genes versus<3 (33.3% and 10.7%, respectively; p< 0.001).Conclusion: This large study confirms the beneficial effect of ESAs and the adverse effect of somatic mutations in patients with LR-MDS

A cell-free approach with a supporting biomaterial in the form of dispersed microspheres induces hyaline cartilage formation in a rabbit knee model

[EN] The objective of this study was to test a regenerative medicine strategy for the regeneration of articular cartilage. This approach combines microfracture of the subchondral bone with the implant at the site of the cartilage defect of a supporting biomaterial in the form of microspheres aimed at creating an adequate biomechanical environment for the differentiation of the mesenchymal stem cells that migrate from the bone marrow. The possible inflammatory response to these biomaterials was previously studied by means of the culture of RAW264.7 macrophages. The microspheres were implanted in a 3¿mm-diameter defect in the trochlea of the femoral condyle of New Zealand rabbits, covering them with a poly(l-lactic acid) (PLLA) membrane manufactured by electrospinning. Experimental groups included a group where exclusively PLLA microspheres were implanted, another group where a mixture of 50/50 microspheres of PLLA (hydrophobic and rigid) and others of chitosan (a hydrogel) were used, and a third group used as a control where no material was used and only the membrane was covering the defect. The histological characteristics of the regenerated tissue have been evaluated 3 months after the operation. We found that during the regeneration process the microspheres, and the membrane covering them, are displaced by the neoformed tissue in the regeneration space toward the subchondral bone region, leaving room for the formation of a tissue with the characteristics of hyaline cartilage.Comisión de Investigaciones Científicas de la Provincia de Buenos Aires (CICPBA), Universidad Nacional de La Plata, Grant/Award Number: 11/X643; Agencia Estatal de Investigación/Fondo Europeo de Desarrollo Regional de la Unión Europea, Grant/Award Number: MAT2016-76039-C4-1 2-R; Spanish Ministry of Economy and Competitiveness (MINECO)Zurriaga Carda, J.; Lastra, ML.; Antolinos-Turpin, CM.; Morales-Román, RM.; Sancho-Tello, M.; Perea-Ruiz, S.; Milián, L.... (2020). A cell-free approach with a supporting biomaterial in the form of dispersed microspheres induces hyaline cartilage formation in a rabbit knee model. Journal of Biomedical Materials Research Part B Applied Biomaterials. 108(4):1428-1438. https://doi.org/10.1002/jbm.b.34490S142814381084Allepuz, A., Martínez, O., Tebé, C., Nardi, J., Portabella, F., & Espallargues, M. (2014). Joint Registries as Continuous Surveillance Systems: The Experience of the Catalan Arthroplasty Register (RACat). The Journal of Arthroplasty, 29(3), 484-490. doi:10.1016/j.arth.2013.07.048Almeida, C. R., Serra, T., Oliveira, M. I., Planell, J. A., Barbosa, M. A., & Navarro, M. (2014). Impact of 3-D printed PLA- and chitosan-based scaffolds on human monocyte/macrophage responses: Unraveling the effect of 3-D structures on inflammation. Acta Biomaterialia, 10(2), 613-622. doi:10.1016/j.actbio.2013.10.035Bell, A. D., Hurtig, M. B., Quenneville, E., Rivard, G.-É., & Hoemann, C. D. (2016). Effect of a Rapidly Degrading Presolidified 10 kDa Chitosan/Blood Implant and Subchondral Marrow Stimulation Surgical Approach on Cartilage Resurfacing in a Sheep Model. CARTILAGE, 8(4), 417-431. doi:10.1177/1947603516676872Bitencourt, C. da S., Silva, L. B. da, Pereira, P. A. T., Gelfuso, G. M., & Faccioli, L. H. (2015). Microspheres prepared with different co-polymers of poly(lactic-glycolic acid) (PLGA) or with chitosan cause distinct effects on macrophages. Colloids and Surfaces B: Biointerfaces, 136, 678-686. doi:10.1016/j.colsurfb.2015.10.011Bonasia, D. E., Martin, J. A., Marmotti, A., Kurriger, G. L., Lehman, A. D., Rossi, R., & Amendola, A. (2015). The use of autologous adult, allogenic juvenile, and combined juvenile–adult cartilage fragments for the repair of chondral defects. Knee Surgery, Sports Traumatology, Arthroscopy, 24(12), 3988-3996. doi:10.1007/s00167-015-3536-5Carmona, L. (2001). The burden of musculoskeletal diseases in the general population of Spain: results from a national survey. Annals of the Rheumatic Diseases, 60(11), 1040-1045. doi:10.1136/ard.60.11.1040Chu, J., Zeng, S., Gao, L., Groth, T., Li, Z., Kong, J., … Li, L. (2016). Poly (L-Lactic Acid) Porous Scaffold-Supported Alginate Hydrogel with Improved Mechanical Properties and Biocompatibility. The International Journal of Artificial Organs, 39(8), 435-443. doi:10.5301/ijao.5000516Conoscenti, G., Schneider, T., Stoelzel, K., Carfì Pavia, F., Brucato, V., Goegele, C., … Schulze-Tanzil, G. (2017). PLLA scaffolds produced by thermally induced phase separation (TIPS) allow human chondrocyte growth and extracellular matrix formation dependent on pore size. Materials Science and Engineering: C, 80, 449-459. doi:10.1016/j.msec.2017.06.011Dashtdar, H., Murali, M. R., Abbas, A. A., Suhaeb, A. M., Selvaratnam, L., Tay, L. X., & Kamarul, T. (2013). PVA-chitosan composite hydrogel versus alginate beads as a potential mesenchymal stem cell carrier for the treatment of focal cartilage defects. Knee Surgery, Sports Traumatology, Arthroscopy, 23(5), 1368-1377. doi:10.1007/s00167-013-2723-5Denlinger, L. C., Fisette, P. L., Garis, K. A., Kwon, G., Vazquez-Torres, A., Simon, A. D., … Corbett, J. A. (1996). Regulation of Inducible Nitric Oxide Synthase Expression by Macrophage Purinoreceptors and Calcium. Journal of Biological Chemistry, 271(1), 337-342. doi:10.1074/jbc.271.1.337Fernández, J. M., Cortizo, M. S., & Cortizo, A. M. (2014). Fumarate/Ceramic Composite Based Scaffolds for Tissue Engineering: Evaluation of Hydrophylicity, Degradability, Toxicity and Biocompatibility. Journal of Biomaterials and Tissue Engineering, 4(3), 227-234. doi:10.1166/jbt.2014.1158García Cruz, D. M., Escobar Ivirico, J. L., Gomes, M. M., Gómez Ribelles, J. L., Sánchez, M. S., Reis, R. L., & Mano, J. F. (2008). Chitosan microparticles as injectable scaffolds for tissue engineering. Journal of Tissue Engineering and Regenerative Medicine, 2(6), 378-380. doi:10.1002/term.106Gordon, S. (2007). The macrophage: Past, present and future. European Journal of Immunology, 37(S1), S9-S17. doi:10.1002/eji.200737638Goyal, D., Keyhani, S., Lee, E. H., & Hui, J. H. P. (2013). Evidence-Based Status of Microfracture Technique: A Systematic Review of Level I and II Studies. Arthroscopy: The Journal of Arthroscopic & Related Surgery, 29(9), 1579-1588. doi:10.1016/j.arthro.2013.05.027Hangody, L., Kish, G., Kárpáti, Z., Udvarhelyi, I., Szigeti, I., & Bély, M. (1998). Mosaicplasty for the Treatment of Articular Cartilage Defects: Application in Clinical Practice. Orthopedics, 21(7), 751-756. doi:10.3928/0147-7447-19980701-04Hoemann, C., Kandel, R., Roberts, S., Saris, D. B. F., Creemers, L., Mainil-Varlet, P., … Buschmann, M. D. (2011). International Cartilage Repair Society (ICRS) Recommended Guidelines for Histological Endpoints for Cartilage Repair Studies in Animal Models and Clinical Trials. CARTILAGE, 2(2), 153-172. doi:10.1177/1947603510397535Kumar, M. N. V. R., Muzzarelli, R. A. A., Muzzarelli, C., Sashiwa, H., & Domb, A. J. (2004). Chitosan Chemistry and Pharmaceutical Perspectives. Chemical Reviews, 104(12), 6017-6084. doi:10.1021/cr030441bKuo, T.-F., Lin, M.-F., Lin, Y.-H., Lin, Y.-C., Su, R.-J., Lin, H.-W., & Chan, W. P. (2011). Implantation of platelet-rich fibrin and cartilage granules facilitates cartilage repair in the injured rabbit knee: preliminary report. Clinics, 66(10), 1835-1838. doi:10.1590/s1807-59322011001000026Landis, J. R., & Koch, G. G. (1977). The Measurement of Observer Agreement for Categorical Data. Biometrics, 33(1), 159. doi:10.2307/2529310Lao, L., Tan, H., Wang, Y., & Gao, C. (2008). Chitosan modified poly(l-lactide) microspheres as cell microcarriers for cartilage tissue engineering. Colloids and Surfaces B: Biointerfaces, 66(2), 218-225. doi:10.1016/j.colsurfb.2008.06.014Lastra, M. L., Molinuevo, M. S., Blaszczyk-Lezak, I., Mijangos, C., & Cortizo, M. S. (2017). Nanostructured fumarate copolymer-chitosan crosslinked scaffold: An in vitro osteochondrogenesis regeneration study. Journal of Biomedical Materials Research Part A, 106(2), 570-579. doi:10.1002/jbm.a.36260Lastra, M. L., Molinuevo, M. S., Cortizo, A. M., & Cortizo, M. S. (2016). Fumarate Copolymer-Chitosan Cross-Linked Scaffold Directed to Osteochondrogenic Tissue Engineering. Macromolecular Bioscience, 17(5). doi:10.1002/mabi.201600219Lebourg, M., Martínez-Díaz, S., García-Giralt, N., Torres-Claramunt, R., Ribelles, J. G., Vila-Canet, G., & Monllau, J. (2013). Cell-free cartilage engineering approach using hyaluronic acid–polycaprolactone scaffolds: A study in vivo. Journal of Biomaterials Applications, 28(9), 1304-1315. doi:10.1177/0885328213507298Luzardo-Alvarez, A., Blarer, N., Peter, K., Romero, J. F., Reymond, C., Corradin, G., & Gander, B. (2005). Biodegradable microspheres alone do not stimulate murine macrophages in vitro, but prolong antigen presentation by macrophages in vitro and stimulate a solid immune response in mice. Journal of Controlled Release, 109(1-3), 62-76. doi:10.1016/j.jconrel.2005.09.015Mainil-Varlet, P., Van Damme, B., Nesic, D., Knutsen, G., Kandel, R., & Roberts, S. (2010). A New Histology Scoring System for the Assessment of the Quality of Human Cartilage Repair: ICRS II. The American Journal of Sports Medicine, 38(5), 880-890. doi:10.1177/0363546509359068Martinez-Diaz, S., Garcia-Giralt, N., Lebourg, M., Gómez-Tejedor, J.-A., Vila, G., Caceres, E., … Monllau, J. C. (2010). In Vivo Evaluation of 3-Dimensional Polycaprolactone Scaffolds for Cartilage Repair in Rabbits. The American Journal of Sports Medicine, 38(3), 509-519. doi:10.1177/0363546509352448McCormick, F., Harris, J. D., Abrams, G. D., Frank, R., Gupta, A., Hussey, K., … Cole, B. (2014). Trends in the Surgical Treatment of Articular Cartilage Lesions in the United States: An Analysis of a Large Private-Payer Database Over a Period of 8 Years. Arthroscopy: The Journal of Arthroscopic & Related Surgery, 30(2), 222-226. doi:10.1016/j.arthro.2013.11.001Sancho-Tello, M., Forriol, F., Gastaldi, P., Ruiz-Saurí, A., Martín de Llano, J. J., Novella-Maestre, E., … Carda, C. (2015). Time Evolution of in Vivo Articular Cartilage Repair Induced by Bone Marrow Stimulation and Scaffold Implantation in Rabbits. The International Journal of Artificial Organs, 38(4), 210-223. doi:10.5301/ijao.5000404Sancho-Tello, M., Forriol, F., de Llano, J. J. M., Antolinos-Turpin, C., Gómez-Tejedor, J. A., Ribelles, J. L. G., & Carda, C. (2017). Biostable Scaffolds of Polyacrylate Polymers Implanted in the Articular Cartilage Induce Hyaline-Like Cartilage Regeneration in Rabbits. The International Journal of Artificial Organs, 40(7), 350-357. doi:10.5301/ijao.5000598Steadman, J. R., Rodkey, W. G., Briggs, K. K., & Rodrigo, J. J. (1999). The microfracture technique to treat full thickness articular cartilage defects of the knee. Der Orthopäde, 28(1), 26-32. doi:10.1007/pl00003545Tetè, S., Mastrangelo, F., Carone, L., Nargi, E., Costanzo, G., Vinci, R., … Ciccarelli, R. (2007). Morphostructural Analysis of Human Follicular Stem Cells on Highly Porous Bone Hydroxyapatite Scaffold. International Journal of Immunopathology and Pharmacology, 20(4), 819-826. doi:10.1177/039463200702000418Van den Borne, M. P. J., Raijmakers, N. J. H., Vanlauwe, J., Victor, J., de Jong, S. N., Bellemans, J., & Saris, D. B. F. (2007). International Cartilage Repair Society (ICRS) and Oswestry macroscopic cartilage evaluation scores validated for use in Autologous Chondrocyte Implantation (ACI) and microfracture. Osteoarthritis and Cartilage, 15(12), 1397-1402. doi:10.1016/j.joca.2007.05.005Vikingsson, L., Sancho-Tello, M., Ruiz-Saurí, A., Díaz, S. M., Gómez-Tejedor, J. A., Ferrer, G. G., … Ribelles, J. L. G. (2015). Implantation of a Polycaprolactone Scaffold with Subchondral Bone Anchoring Ameliorates Nodules Formation and Other Tissue Alterations. The International Journal of Artificial Organs, 38(12), 659-666. doi:10.5301/ijao.5000457Zan, Q., Wang, C., Dong, L., Cheng, P., & Tian, J. (2008). Effect of surface roughness of chitosan-based microspheres on cell adhesion. Applied Surface Science, 255(2), 401-403. doi:10.1016/j.apsusc.2008.06.074Zhang, C., Cai, Y., & Lin, X. (2016). One-Step Cartilage Repair Technique as a Next Generation of Cell Therapy for Cartilage Defects: Biological Characteristics, Preclinical Application, Surgical Techniques, and Clinical Developments. Arthroscopy: The Journal of Arthroscopic & Related Surgery, 32(7), 1444-1450. doi:10.1016/j.arthro.2016.01.061Zhu, W., Chen, K., Lu, W., Sun, Q., Peng, L., Fen, W., … Zeng, Y. (2013). In vitro study of nano-HA/PLLA composite scaffold for rabbit BMSC differentiation under TGF-β1 induction. In Vitro Cellular & Developmental Biology - Animal, 50(3), 214-220. doi:10.1007/s11626-013-9699-

Micropartículas de PLLA y CHT como andamiaje para la regeneración del cartílago articular : modelo animal.

The avascular nature of cartilaginous tissue has historically lead to bad prognosis in osteochondral injuries. One of the possible treatment options of these injuries is the use of scaffolds, being superior to other options that obtain a fibrous cartilage as a result. We have elaborated PLLA and CHT microspheres as a scaffold for the treatment of osteochondral injuries carried out in albine New Zealand rabbits. They were distributed into groups with different proportions of microspheres, having also a control group with untreated injuries. Native cartilage of the contralateral knees was also analysed. Samples were evaluated in order to establish the quality of the cartilage obtained (using de macroscopic ICRS, microscopic ICRS II scales and a histomorphometric study).The groups with microspheres obtained a regeneration cartilage with hyaline characteristics, a good cell distribution and regular surface. The control group resulted in a cartilage with worse organization and an irregular surface

Bevacizumab Diminishes Inflammation in an Acute Endotoxin-Induced Uveitis Model

Introduction: Uveitis is an eye disease characterized by inflammation of the uvea and an early and exhaustive diagnosis is essential for its treatment. The aim of our study is to assess the potential toxicity and anti-inflammatory efficacy of Bevacizumab in an experimental uveitis model by subcutaneously injecting lipopolysaccharide into Lewis rats and to clarify its mechanism.Material and Methods: Blood–aqueous barrier integrity was assessed 24 h after endotoxin-induced uveitis (EIU) by analyzing two parameters: cell count and protein concentration in aqueous humors. Histopathology of all eye structures was also studied. Enzyme-linked immunosorbent analyses of the aqueous humor samples were performed in order to calculate the diverse chemokine and cytokine protein levels and oxidative stress-related markers were also evaluated.Results: The aqueous humor’s cellular content significantly increased in the group treated with only Bevacizumab, but it had no effect on retina histopathological grading. Nevertheless, the inflammation noted in ocular structures when administering Bevacizumab with endotoxin was mostly prevented since aqueous humor cell content considerably lowered, and concomitantly with a sharp drop in uveal, vitreous, and retina histopathological grading. The values of the multi-faceted cytokine IL-2 also significantly decreased (p &lt; 0.05 vs. endotoxin group), and the protective IL-6 and IL-10 cytokines values rose with related anti-oxidant system recovery (p &lt; 0.05 vs. endotoxin group). Concurrently, some related M1 macrophage chemokines substantially increased, e.g., GRO/KC, a chemokine that also displays any kind of protective role.Conclusion: All these results revealed that 24 h after being administered, Bevacizumab treatment in EIU significantly prevented inflammation in various eye structures and correct results in efficacy vs. toxicity balance were obtained