The rising number of patients needing renal replacement therapy, alongside the significant clinical and economic limitations of current therapies, creates an imperative need for new strategies to treat kidney diseases. Kidney bioengineering through the production of acellular scaffolds and recellularization with stem cells is one potential strategy. While protocols for obtaining organ scaffolds have been developed successfully, scaffold recellularization is more challenging. We evaluated the potential of in vivo and in vitro kidney scaffold recellularization procedures. Our results show that acellular scaffolds implanted in rats cannot be repopulated with host cells, and in vitro recellularization is necessary. However, we obtained very limited and inconsistent cell seeding when using different infusion protocols, regardless of injection site. We also obtained experimental and theoretical data indicating that uniform cell delivery into the kidney scaffolds cannot be obtained using these infusion protocols, due to the permeability of the extracellular matrix of the scaffold. Our results highlight the major physical barriers that limit in vitro recellularization of acellular kidney scaffolds and the obstacles that must be investigated to effectively advance this strategy for regenerative medicine.
The aim of this study was to identify a method for modifying the time-dependent viscoelastic properties of gels without altering the elastic component. To this end, two hydrogels commonly used in biomedical applications, agarose and acrylamide, were prepared in aqueous solutions of dextran with increasing concentrations (0, 2 and 5% w/v) and hence increasing viscosities. Commercial polyurethane sponges soaked in the same solutions were used as controls, since, unlike in hydrogels, the liquid in these sponge systems is poorly bound to the polymer network. Sample viscoelastic properties were characterised using the epsilon-dot method, based on compression tests at different constant strain-rates. Experimental data were fitted to a standard linear solid model. While increasing the liquid viscosity in the controls resulted in a significant increase of the characteristic relaxation time ( ), both the instantaneous () and the equilibrium ( ) elastic moduli remained almost constant.However, in the hydrogels a significant reduction of both and was observed. On the other hand, as expected,an indicator of the equilibrium elastic behaviour after the occurrence of viscoelastic relaxation dynamicswas found to be independent of the liquid phase viscosity.Therefore, although the elastic and viscous components of hydrogels cannot be completely decoupled due to the interaction of the liquid and solid phases, we show that their viscoelastic behaviour can be modulated by varying the viscosity of the aqueous phase. This simple-yet-effective strategy could be useful in the field of mechanobiology, particularly for studying cell response to substrate viscoelasticity while keeping the elastic cue (i.e. equilibrium modulus, or quasi-static stiffness) constant.
We describe the engineering design, computational modeling, and empirical performance of a moving air–liquid interface (MALI) bioreactor for the study of aerosol deposition on cells cultured on an elastic, porous membrane which mimics both air–liquid interface exposure conditions and mechanoelastic motion of lung tissue during breathing. The device consists of two chambers separated by a cell layer cultured on a porous, flexible membrane. The lower (basolateral) chamber is perfused with cell culture medium simulating blood circulation. The upper (apical) chamber representing the air compartment of the lung is interfaced to an aerosol generator and a pressure actuation system. By cycling the pressure in the apical chamber between 0 and 7 kPa, the membrane can mimic the periodic mechanical strain of the alveolar wall. Focusing on the engineering aspects of the system, we show that membrane strain can be monitored by measuring changes in pressure resulting from the movement of media in the basolateral chamber. Moreover, liquid aerosol deposition at a high dose delivery rate (>1 µl cm−2 min−1) is highly efficient (ca. 51.5%) and can be accurately modeled using finite element methods. Finally, we show that lung epithelial cells can be mechanically stimulated under air–liquid interface and stretch‐conditions without loss of viability. The MALI bioreactor could be used to study the effects of aerosol on alveolar cells cultured at the air–liquid interface in a biodynamic environment or for toxicological or therapeutic applications.
The aim of this review is to provide a systematic design guideline to users, particularly engineers interested in developing and deploying lung models, and biologists seeking to identify a suitable platform for conducting in vitro experiments involving pulmonary cells or tissues. We first discuss the state of the art on lung in vitro models, describing the most simplistic and traditional ones. Then, we analyze in further detail the more complex dynamic engineered systems that either provide mechanical cues, or allow for more predictive exposure studies, or in some cases even both. This is followed by a dedicated section on microchips of the lung. Lastly, we present a critical discussion of the different characteristics of each type of system and the criteria which may help researchers select the most appropriate technology according to their specific requirements. Readers are encouraged to refer to the tables accompanying the different sections where comprehensive and quantitative information on the operating parameters and performance of the different systems reported in the literature is provided.
Children with cerebral palsy (CP) suffer deficits in their motor, sensory, and cognitive abilities, as well as in their visuospatial competences. In the last years, several authors have tried to correlate the visuospatial abilities with the navigational ones. Given their importance in everyday functions, navigation skills have been deeply studied using increasingly cutting-edge techniques such as virtual reality (VR). However, to our knowledge, there are no studies focused on training using immersive VR (IVR) in children with movement disorders. For this reason, we proposed an IVR training to 35 young participants with CP and conceived to improve their navigation skills in a “simil-real” environment while playing on a dynamic platform. A subgroup performed a part of the training which was specifically dedicated to the use of the allocentric strategy (i.e., looking for landmarks) to navigate the virtual environment. We then compared the children’s navigation and spatial skills pre- and post-intervention. All the children improved their visual–spatial abilities; particularly, if the IVR activities specifically trained their ability to look for landmarks and use them to navigate. The results of this work highlight the potential of an IVR training program to increase the navigation abilities of patients with CPs.
Nano and micro particles are widely used in industrial, household and medicinal applications. To understand the interaction between particles and epithelial cells, we developed a dynamic model of the alveolar interface. This system, named DALI (Dynamic Model for the ALveolar Interface), is a modular bioreactor composed of two chambers divided by a porous membrane where epithelial lung cells are seeded. The membrane is the support of the alveolar barrier that separates the two compartments of the alveolus: the air and blood side. The system integrates the following elements: i) Air/Liquid interface, thanks to the two chambers divided by the membrane: ii) Cell culture media flow, thanks to the presence of a peristaltic pump; iii) Lung breathing motion, thanks to an airflow that allows the stretching of the membrane; iv) Aerosol deposition system, to study the effects of drug efficacy or particle toxicity on the epithelial layer; v) Quartz Crystal Microbalance, to quantify the amount of aerosolized particles.
Game activity is fundamental for children’s cognitive and social development. During recent years, technology development has led to changes in several areas, including the ludic one. However, while in the literature, there are plenty of studies that report the importance of technology-based games in rehabilitation program, little attention has been paid to their role as pure entertainment. In contrast, the market does not provide videogames that are engaging, accessible, and inclusive. In this context, a survey was distributed to families who have a child with neuromotor limitations to investigate how these children deal with play, in particular with videogames, and what the requirements are for accessible and inclusive videogames. FightTheStroke distributed the questionnaire to families with a child with neuromotor impairments in April 2020. Fifty-six families responded to the survey. The answers revealed that children generally manifest positive feelings when playing with videogames, especially with cooperative ones, even if they are not fully accessible. The survey also collected user needs and suggestions from families about the design of videogames for neuromotor-impaired children. Guidelines derived from the survey are reported for the development of entertaining, inclusive, and accessible videogames, playable by children with neuromotor disabilities.
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