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Acute kidney injury (AKI) is defined as a decrease in kidney function within hours, which encompasses both injury and impairment of renal function. AKI is not considered a pathological condition of single organ failure, but a syndrome in which the kidney plays an active role in the progression of multi-organ dysfunction. The incidence rate of AKI is increasing and becoming a common (8-16% of hospital admissions) and serious disease (four-fold increased hospital mortality) affecting public health costs worldwide. AKI also affects the young and previously healthy individuals affected by infectious diseases in Latin America. Because of the multifactorial pathophysiological mechanisms, there is no effective pharmacological therapy that prevents the evolution or reverses the injury once established; therefore, renal replacement therapy is the only current alternative available for renal patients. The awareness of an accurate and prompt recognition of AKI underlying the various clinical phenotypes is an urgent need for more effective therapeutic interventions to diminish mortality and socio-economic impacts of AKI. The use of biomarkers as an indicator of the initial stage of the disease is critical and the cornerstone to fulfill the gaps in the field. This review discusses emerging strategies from basic science toward the anticipation of features, treatment of AKI, and new treatments using pharmacological and stem cell therapies. We will also highlight bioartificial kidney studies, addressing the limitations of the development of this innovative technology.

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Tissue engineered (or bioengineered) tracheas are alternative options under investigation when the resection with end-to-end anastomosis cannot be performed. One approach to develop bioengineered tracheas is a complex process that involves the use of decellularized tissue scaffolds, followed by recellularization in custom-made tracheal bioreactors. Tracheas withstand pressure variations and their biomechanics are of great importance so that they do not collapse during respiration, although there has been no preferred method of mechanical assay of tracheas among several laboratories over the years. These methods have been performed in segments or whole tracheas and in different species of mammals. This article aims to present some methods used by different research laboratories to evaluate the mechanics of tracheal grafts and presents the importance of the tracheal biomechanics in both macro and micro scales. If bioengineered tracheas become a reality in hospitals in the next few years, the standardization of biomechanical parameters will be necessary for greater consistency of results before transplantations.

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Tympanic membrane perforations are due to common otologic problems. The current treatments to heal tympanic membrane perforation, such as myringoplasty, have some disadvantages, including the need for autologous grafting, which is rapidly absorbed by the organism before perforation recovery is complete. To improve the structural and functional tympanic membrane healing after surgery, we propose a new branch of artificial grafts. In this study, we report the development of artificial grafts using electrospun bioabsorbable polymers. Polymers such as poly (l-lactic acid) and poly (lactic-co-glycolic acid) acted as the scaffold for cell growth in a co-culture of fibroblasts and keratinocytes. This co-culture promoted the growth of an epithelial-equivalent tissue over the electrospun scaffold, which was used as an alternative graft in myringoplasty. The in vivo study was performed in Sprague Dawley rats. Ear endoscopy was performed 30days after surgery and showed that tympanic membrane perforations treated with artificial grafts healed naturally, completely and with the possibility of maintaining their actual functionality. In conclusion, our study described a new artificial graft created specifically to fulfill the requirements of perforated tympanic membrane healing processes, which are compatibility, proper durability and less intense side effects following myringoplasty.

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The aim of this study was to construct a full-thickness artificial cornea substitute in vitro by coculturing limbal epithelial cell-like (LEC-like) cells and corneal endothelial cell-like (CEC-like) cells derived from human embryonic stem cells (hESCs) on APCM scaffold. A 400 µm thickness, 11 mm diameter APCM lamella containing Bowman's membrane was prepared as the scaffold using trephine and a special apparatus made by ourselves. LEC-like cells and CEC-like cells, derived from hESCs as our previously described, were cocultured on the scaffold using a special insert of 24-well plates that enabled seeding both sides of the scaffold. Three or four layers of epithelium-like cells and a uniform monolayer of CEC-like cells could be observed by H&E staining. The thickness, endothelial cell density, and mechanical properties of the construct were similar to that of native rabbit corneas. Immunofluorescence analysis showed expression of ABCG2 and CK3 in the epithelium-like cell layers and expression of N-cadherin, ZO-1 and Na+/K + ATPase in the CEC-like cells. The corneal substitutes were well integrated within the host corneas, and the transparency increased gradually in 8-week follow-up after transplantation in the rabbits. These results suggest that the strategy we developed is feasible and effective for construction of tissue-engineered full-thickness cornea substitute with critical properties of native cornea.

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Regenerative medicine is a medical multidisciplinary area with the aim of morphologic and functional restoration of tissues or organs in order to re-establish normal function. The main bases of regenerative medicine are the use of autologous stem or progenitor cells and the ex vivo construction of physical-mechanical tissue structuring organization, which with stem cells may form bioartificial organs. Another eventual strategy is in vivo stem or progenitor cell stimulation for proliferation. Tissue engineering entirely combines the use of cells, biochemical and physicochemical factors, nanomaterials and bioengineering methods to improve or replace biological functions of tissues and organs. The progressive understanding of the proliferation and differentiation of the process of stem cells and their in vitro manipulation has been the launching platform for the field of regenerative medicine. In this review we describe the main strategies used for regenerative medicine in tissue regeneration along with the main obtained clinicalsurgical benefits.

La medicina regenerativa es una área multidisciplinaria destinada a la recuperación morfológica y funcional de tejidos y órganos severamente lesionados. Los principales recursos que emplea la medicina regenerativa son: células madre o troncales autólogas, y moldes estructurales de soporte físico-mecánico tisular construidos ex vivo, que pueden formar órganos bioartificiales; otra posibilidad es la estimulación de células madre in vivo para su proliferación. La ingeniería tisular combina, integralmente, el uso de células, factores bioquímicos y físicos, nanomateriales y métodos de bioingeniería para mejorar o remplazar las funciones biológicas de tejidos y órganos. El entendimiento progresivo de los procesos de proliferación y diferenciación celulares, y la manipulación in vitro de las células madre, ha sido la plataforma del desarrollo de la medicina regenerativa. En esta revisión se describen las diferentes estrategias que utiliza la medicina regenerativa en la regeneración de tejidos, y los principales beneficios clínico-quirúrgicos conseguidos con su aplicación.

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OBJECTIVE: To report the experience of the Federal University of São Paulo, Brazil, in performing Boston keratoprosthesis type 1 implantation in the developing world. METHODS: We analyzed 30 eyes of 30 patients who underwent Boston type 1 keratoprosthesis surgery between 2008 and 2012 in a prospective interventional study. Preoperative, perioperative, and postoperative parameters were analyzed, including visual acuity (VA), keratoprosthesis stability, and postoperative complications. RESULTS: Preoperative diagnoses were failed grafts in 16 eyes (53.33%), chemical injury in 10 eyes (33.33%) and Stevens-Johnson syndrome in 4 eyes (13.33%). Also, 16 eyes (53.33%) had preoperative glaucoma. Preoperative best corrected VA ranged from 20/400 to light perception. With an average follow-up of 32 months (range 1-55 months), postoperative vision improved to >20/200 in 24 eyes (80%). Postoperative VA was statistically improved compared with the preoperative measurement during all postoperative follow-ups (up to 36 months). During the follow-up period (32 months), retention of the initial keratoprosthesis was 93.3%. The incidence of retroprosthetic membrane was 26.66%. Progression of glaucoma occurred in 7 of 16 eyes (43%). Three patients experienced development of glaucoma after keratoprosthesis implantation. One eye experienced development of infectious keratitis, and 2 eyes had retinal detachment. CONCLUSIONS: Performing Boston type 1 keratoprosthesis in a developing country is a viable option after multiple keratoplasty failures and conditions with a poor prognosis for keratoplasty. Our experience appears similar to major reports in the field from investigators in developed countries. Adjustments to postoperative management must be considered according to the particular location.

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The use of fibrin in tissue engineering has greatly increased over the last 10 years. The aim of this research was to develop a mathematical model to relate the microcapsule-size and cell-load to growth and oxygen depletion. Keratinocytes were isolated from rat skins and microencapsulated dropping fibrinogen and thrombin solutions. The cell growth was measured with MTT-assay and confirmed using histochemical technique. The oxygen was evaluated using a Clark sensor. It was found that Fick-Monod model explained the cell growth for the first 48 h, but overestimated the same thereafter. It was necessary to add a logistic equation to reach valid results. In relation to the preferred implant alternative, when considering large initial cell loads, the possibility to implant small loads of fast-growing cells arises from the simulations. In relation to the microcapsule size, it was found that a critical diameter could be established from which cell growth velocity is about the same.

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