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.
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