Biofabrication Strategies and Engineered In Vitro Systems for Vascular Mechanobiology.

The vascular system is integral for maintaining organ-specific functions and homeostasis. Dysregulation in vascular architecture and function can lead to various chronic or acute disorders. Investigation of the role of the vascular system in health and disease has been accelerated through the development of tissue-engineered constructs and microphysiological on-chip platforms. These in vitro systems permit studies of biochemical regulation of vascular networks and parenchymal tissue and provide mechanistic insights into the biophysical and hemodynamic forces acting in organ-specific niches. Detailed understanding of these forces and the mechanotransductory pathways involved is necessary to develop preventative and therapeutic strategies targeting the vascular system. This review describes vascular structure and function, the role of hemodynamic forces in maintaining vascular homeostasis, and measurement approaches for cell and tissue level mechanical properties influencing vascular phenomena. State-of-the-art techniques for fabricating in vitro microvascular systems, with varying degrees of biological and engineering complexity, are summarized. Finally, the role of vascular mechanobiology in organ-specific niches and pathophysiological states, and efforts to recapitulate these events using in vitro microphysiological systems, are explored. It is hoped that this review will help readers appreciate the important, but understudied, role of vascular-parenchymal mechanotransduction in health and disease toward developing mechanotherapeutics for treatment strategies.

Accurate flow in augmented networks (AFAN): an approach to generating three-dimensional biomimetic microfluidic networks with controlled flow.

In vivo, microvasculature provides oxygen, nutrients, and soluble factors necessary for cell survival and function. The highly tortuous, densely-packed, and interconnected three-dimensional (3D) architecture of microvasculature ensures that cells receive these crucial components. The ability to duplicate microvascular architecture in tissue-engineered models could provide a means to generate large-volume constructs as well as advanced microphysiological systems. Similarly, the ability to induce realistic flow in engineered microvasculature is crucial to recapitulating in vivo-like flow and transport. Advanced biofabrication techniques are capable of generating 3D, biomimetic microfluidic networks in hydrogels, however, these models can exhibit systemic aberrations in flow due to incorrect boundary conditions. To overcome this problem, we developed an automated method for generating synthetic augmented channels that induce the desired flow properties within three-dimensional microfluidic networks. These augmented inlets and outlets enforce the appropriate boundary conditions for achieving specified flow properties and create a three-dimensional output useful for image-guided fabrication techniques to create biomimetic microvascular networks.

Tangential Flow Microfiltration for Viral Separation and Concentration.

Microfluidic devices that allow biological particle separation and concentration have found wide applications in medical diagnosis. Here we present a viral separation polydimethylsiloxane (PDMS) device that combines tangential flow microfiltration and affinity capture to enrich HIV virus in a single flow-through fashion. The set-up contains a filtration device and a tandem resistance channel. The filtration device consists of two parallel flow channels separated by a polycarbonate nanoporous membrane. The resistance channel, with dimensions design-guided by COMSOL simulation, controls flow permeation through the membrane in the filtration device. A flow-dependent viral capture efficiency is observed, which likely reflects the interplay of several processes, including specific binding of target virus, physical deposition of non-specific particles, and membrane cleaning by shear flow. At the optimal flow rate, nearly 100% of viral particles in the permeate are captured on the membrane with various input viral concentrations. With its easy operation and consistent performance, this microfluidic device provides a potential solution for HIV sample preparation in resource-limited settings.

Fundamentals of Laser-Based Hydrogel Degradation and Applications in Cell and Tissue Engineering.

The cell and tissue engineering fields have profited immensely through the implementation of highly structured biomaterials. The development and implementation of advanced biofabrication techniques have established new avenues for generating biomimetic scaffolds for a multitude of cell and tissue engineering applications. Among these, laser-based degradation of biomaterials is implemented to achieve user-directed features and functionalities within biomimetic scaffolds. This review offers an overview of the physical mechanisms that govern laser-material interactions and specifically, laser-hydrogel interactions. The influences of both laser and material properties on efficient, high-resolution hydrogel degradation are discussed and the current application space in cell and tissue engineering is reviewed. This review aims to acquaint readers with the capability and uses of laser-based degradation of biomaterials, so that it may be easily and widely adopted.