Engineered modular microphysiological models of the human airway clearance phenomena.

Mucociliary clearance is a crucial mechanism that supports the elimination of inhaled particles, bacteria, pollution, and hazardous agents from the human airways, and it also limits the diffusion of aerosolized drugs into the airway epithelium. In spite of its relevance, few in vitro models sufficiently address the cumulative effect of the steric and interactive barrier function of mucus on the one hand, and the dynamic mucus transport imposed by ciliary mucus propulsion on the other hand. Here, ad hoc mucus models of physiological and pathological mucus are combined with magnetic artificial cilia to model mucociliary transport in both physiological and pathological states. The modular concept adopted in this study enables the development of mucociliary clearance models with high versatility since these can be easily modified to reproduce phenomena characteristic of healthy and diseased human airways while allowing to determine the effect of each parameter and/or structure separately on the overall mucociliary transport. These modular airway models can be available off-the-shelf because they are exclusively made of readily available materials, thus ensuring reproducibility across different laboratories.

From tissue engineering to engineering tissues: the role and application of in vitro models.

Engineered models have emerged as relevant in vitro tools to foresee the translational potential of new therapies from the bench to the bedside in a fast and cost-effective fashion. The principles applied to the development of tissue-engineered constructs bring the foundation concepts to engineer relevant in vitro models. Engineered models often face scepticism, because regularly these do not include the extreme complexity of nature, but rather a simplification of a phenomenon. While engineering in vitro models, a hypothesis is imposed towards which defined parameters are included to assess the degree of similarity between the in vitro model and the native phenomenon, keeping in mind their intrinsic limitations. The development of in vitro models has been highly supported and disseminated by different regulatory agencies. This review aims at defining and exploring the multifaceted potential of tangible, not theoretical, models within the biomedical field to represent physiological tissues and organ-related phenomena.