Alveolus Lung-on-a-Chip Platform: A Proposal.

Respiratory diseases are top-ranked causes of deaths and disabilities around the world, making new approaches to the treatment necessary. In recent years, lung-on-a-chip platforms have emerged as a potential candidate to replace animal experiments because they can successfully simulate human physiology. In this review, we discuss the main respiratory diseases and their pathophysiology, how to model a lung microenvironment, and how to translate it to clinical applications. Furthermore, we propose a novel alveolus lung-on-a-chip platform, based on all currently available methodologies. This review provides solutions and new ideas to improve the alveolar lung-on-a-chip platform. Finally, we provided evidence that approaches such as 3D printing, organ-a-chip devices and organoids can be used in combination, and some challenges could be overcome.post-print1239 K

Behavior of vascular resistance undergoing various pressure insufflation and perfusion on decellularized lungs

Bioengineering of functional lung tissue by using whole lung scaffolds has been proposed as a potential alternative for patients awaiting lung transplant. Previous studies have demonstrated that vascular resistance (Rv) could be altered to optimize the process of obtaining suitable lung scaffolds. Therefore, this work was aimed at determining how lung inflation (tracheal pressure) and perfusion (pulmonary arterial pressure) affect vascular resistance. This study was carried out using the lungs excised from 5 healthy male Sprague-Dawley rats. The trachea was cannulated and connected to a continuous positive airway pressure (CPAP) device to provide a tracheal pressure ranging from 0 to 15 cmH(2)O. The pulmonary artery was cannulated and connected to a controlled perfusion system with continuous pressure (gravimetric level) ranging from 5 to 30 cmH(2)O. Effective Rv was calculated by ratio of pulmonary artery pressure (P-PA) by pulmonary artery flow (V'(PA)). Rv in the decellularized lungs scaffolds decreased at increasing V'(PA), stabilizing at a pulmonary arterial pressure greater than 20 cmH(2)O. On the other hand, CPAP had no influence on vascular resistance in the lung scaffolds after being subjected to pulmonary artery pressure of 5 cmH(2)O. In conclusion, compared to positive airway pressure, arterial lung pressure markedly influences the mechanics of vascular resistance in decellularized lungs. (C) 2016 Elsevier Ltd. All rights reserved

Photobiomodulation Therapy Restores IL-10 Secretion in a Murine Model of Chronic Asthma: Relevance to the Population of CD4+CD25+Foxp3+ Cells in Lung.

It is largely known that photobiomodulation (PBM) has beneficial effects on allergic pulmonary inflammation. Our previous study showed an anti-inflammatory effect of the PBM in an acute experimental model of asthma, and we see that this mechanism is partly dependent on IL-10. However, it remains unclear whether the activation of regulatory T cells is mediated by PBM in a chronic experimental model of asthma. In this sense, the objective of this study was to verify the anti-inflammatory role of the PBM in the pulmonary inflammatory response in a chronic experimental asthma model. The protocol used for asthma induction was the administration of OVA subcutaneously (days 0 and 14) and intranasally (3 times/week, for 5 weeks). On day 50, the animals were sacrificed for the evaluation of the different parameters. The PBM used was the diode, with a wavelength of 660 nm, a power of 100 mW, and 5 J for 50 s/point, in three different application points. Our results showed that PBM decreases macrophages, neutrophils, and lymphocytes in the bronchoalveolar lavage fluid (BALF). Moreover, PBM decreased the release of cytokines by the lung, mucus, and collagen in the airways and pulmonary mechanics. When we analyzed the percentage of Treg cells in the group irradiated with laser, we verified an increase in these cells, as well as the release of IL-10 in the BALF. Therefore, we conclude that the use of PBM therapy in chronic airway inflammation attenuated the inflammatory process, as well as the pulmonary functional and structural parameters, probably due to an increase in Treg cells.post-print1951 K

TÉCNICA DE DESCELULARIZAÇÃO DE PULMÕES PARA A BIOENGENHARIA DE ÓRGÃOS

As principais doenças do sistema respiratório, tais como a obstrução pulmonar crônica, o enfisema pulmonar, a fibrose pulmonar idiopática e a hipertensão arterial pulmonar primária, tem como resultado um dano estrutural no parênquima pulmonar irreversível, sendo o transplante pulmonar a única indicação terapêutica. Infelizmente, o sucesso do transplante pulmonar é limitado, principalmente devido à escassez do número de doadores de órgãos e incidência de bronquiolite obliterante o que resulta em uma resposta aloimune provocada pelas disparidades entre o doador e os antígenos do receptor. Neste contexto, a bioengenharia de pulmões é considerada uma alternativa terapêutica em potencial. Este estudo visa demonstrar em um modelo experimental animal o processo de descelularização de pulmões visando a preparação de scaffolds para a recriação artificial de órgãos. A matriz de órgãos descelularizados, potencialmente, mantém a arquitetura tridimensional e a composição bioquímica, bem como a microvasculatura do tecido original. Esta capacidade torna o pulmão descelularizado promissor para a geração bioartificial de pulmões funcionais

Effects of two different decellularization routes on the mechanical properties of decellularized lungs

Considering the limited number of available lung donors, lung bioengineering using whole lung scaffolds has been proposed as an alternative approach to obtain lungs suitable for transplantation. However, some decellularization protocols can cause alterations on the structure, composition, or mechanical properties of the lung extracellular matrix. Therefore, the aim of this study was to compare the acellular lung mechanical properties when using two different routes through the trachea and pulmonary artery for the decellularization process. This study was performed by using the lungs excised from 30 healthy male C57BL/6 mice, which were divided into 3 groups: tracheal decellularization (TDG), perfusion decellularization (PDG), and control groups (CG). Both decellularized groups were subjected to decellularization protocol with a solution of 1% sodium dodecyl sulfate. The behaviour of mechanical properties of the acellular lungs was measured after decellularization process. Static (Est) and dynamic (Edyn) elastances were obtained by the end-inspiratory occlusion method. TDG and PDG showed reduced Est and Edyn elastances after lung decellularization. Scanning electron microscopy showed no structural changes after lung decellularization of the TDG and PDG. In conclusion, was demonstrated that there is no significant difference in the behaviour of mechanical properties and extracellular matrix of the decellularized lungs by using two different routes through the trachea and pulmonary artery

Low-Level Laser Therapy Reduces Lung Inflammation in an Experimental Model of Chronic Obstructive Pulmonary Disease Involving P2X7 Receptor

Chronic obstructive pulmonary disease (COPD) is a progressive disease characterized by irreversible airflow limitation, airway inflammation and remodeling, and enlargement of alveolar spaces. COPD is in the top five leading causes of deaths worldwide and presents a high economic cost. However, there are some preventive measures to lower the risk of developing COPD. Low-level laser therapy (LLLT) is a new effective therapy, with very low cost and no side effects. So, our objective was to investigate if LLLT reduces pulmonary alterations in an experimental model of COPD. C57BL/6 mice were submitted to cigarette smoke for 75 days (2x/day). After 60 days to smoke exposure, the treated group was submitted to LLLT (diode laser, 660 nm, 30 mW, and 3 J/cm(2)) for 15 days and euthanized for morphologic and functional analysis of the lungs. Our results showed that LLLT significantly reduced the number of inflammatory cells and the proinflammatory cytokine secretion such as IL-1 beta, IL-6, and TNF-alpha in bronchoalveolar lavage fluid (BALF). We also observed that LLLT decreased collagen deposition as well as the expression of purinergic P2X7 receptor. On the other hand, LLLT increased the IL-10 release. Thus, LLLT can be pointed as a promising therapeutic approach for lung inflammatory diseases as COPD.Sao Paulo Research Foundation (FAPESP) [2012/16498-5, 2012/15165-2]FAPESP [2015/23152-6, 2014/14604-8, 2015/13486-4]Univ Nove Julho UNINOVE, Post Grad Program Biophoton Appl Hlth Sci, Sao Paulo, SP, BrazilBrazilian Inst Teaching & Res Pulm & Exercise Imm, Sao Jose Dos Campos, SP, BrazilUniv Nove Julho UNINOVE, Masters Degree & PhD Program Rehabil Sci, Expt Cardioresp Physiol Lab, Sao Paulo, SP, BrazilUniv Calif San Diego UCSD Hlth Sci, Div Trauma Surg Crit Care Burns & Acute Care Surg, Dept Surg, San Diego, CA USAFed Univ Sao Paulo UNIFESP, Inst Sci & Technol, Sao Jose Dos Campos, SP, BrazilUniv Brasil, Postgrad Program Bioengn, Sao Paulo, SP, BrazilFed Univ Sao Paulo UNIFESP, Postgrad Program Sci Human Movement & Rehabil, Santos, SP, BrazilFed Univ Sao Paulo UNIFESP, Inst Sci & Technol, Sao Jose Dos Campos, SP, BrazilFed Univ Sao Paulo UNIFESP, Postgrad Program Sci Human Movement & Rehabil, Santos, SP, BrazilFAPESP [2012/16498-5, 2012/15165-2]FAPESP [2015/23152-6, 2014/14604-8, 2015/13486-4]Web of Scienc

Behavior of vascular resistance undergoing various pressure insufflation and perfusion on decellularized lungs

Bioengineering of functional lung tissue by using whole lung scaffolds has been proposed as a potential alternative for patients awaiting lung transplant. Previous studies have demonstrated that vascular resistance (Rv) could be altered to optimize the process of obtaining suitable lung scaffolds. Therefore, this work was aimed at determining how lung inflation (tracheal pressure) and perfusion (pulmonary arterial pressure) affect vascular resistance. This study was carried out using the lungs excised from 5 healthy male Sprague-Dawley rats. The trachea was cannulated and connected to a continuous positive airway pressure (CPAP) device to provide a tracheal pressure ranging from 0 to 15 cmH(2)O. The pulmonary artery was cannulated and connected to a controlled perfusion system with continuous pressure (gravimetric level) ranging from 5 to 30 cmH(2)O. Effective Rv was calculated by ratio of pulmonary artery pressure (P-PA) by pulmonary artery flow (V'(PA)). Rv in the decellularized lungs scaffolds decreased at increasing V'(PA), stabilizing at a pulmonary arterial pressure greater than 20 cmH(2)O. On the other hand, CPAP had no influence on vascular resistance in the lung scaffolds after being subjected to pulmonary artery pressure of 5 cmH(2)O. In conclusion, compared to positive airway pressure, arterial lung pressure markedly influences the mechanics of vascular resistance in decellularized lungs. (C) 2016 Elsevier Ltd. All rights reserved

Behavior of vascular resistance undergoing various pressure insufflation and perfusion on decellularized lungs

Bioengineering of functional lung tissue by using whole lung scaffolds has been proposed as a potential alternative for patients awaiting lung transplant. Previous studies have demonstrated that vascular resistance (Rv) could be altered to optimize the process of obtaining suitable lung scaffolds. Therefore, this work was aimed at determining how lung inflation (tracheal pressure) and perfusion (pulmonary arterial pressure) affect vascular resistance. This study was carried out using the lungs excised from 5 healthy male Sprague-Dawley rats. The trachea was cannulated and connected to a continuous positive airway pressure (CPAP) device to provide a tracheal pressure ranging from 0 to 15 cmH(2)O. The pulmonary artery was cannulated and connected to a controlled perfusion system with continuous pressure (gravimetric level) ranging from 5 to 30 cmH(2)O. Effective Rv was calculated by ratio of pulmonary artery pressure (P-PA) by pulmonary artery flow (V'(PA)). Rv in the decellularized lungs scaffolds decreased at increasing V'(PA), stabilizing at a pulmonary arterial pressure greater than 20 cmH(2)O. On the other hand, CPAP had no influence on vascular resistance in the lung scaffolds after being subjected to pulmonary artery pressure of 5 cmH(2)O. In conclusion, compared to positive airway pressure, arterial lung pressure markedly influences the mechanics of vascular resistance in decellularized lungs. (C) 2016 Elsevier Ltd. All rights reserved