While considerable progress has been made in studying genetic and cellular aspects of metastasis with in vitro cell culture and in vivo animal models, the driving mechanisms of each step of metastasis are still relatively unclear due to their complexity. Moreover, little progress has been made in understanding how cellular fitness in one step of the metastatic cascade correlates with ability to survive other subsequent steps. Engineered models incorporate tools such as tailored biomaterials and microfabrication to mimic human disease progression, which when coupled with advanced quantification methods permit comparisons to human patient samples and in vivo studies. Here, we review novel tools and techniques that have been recently developed to dissect key features of the metastatic cascade using primary patient samples and highly representative microenvironments for the purposes of advancing personalized medicine and precision oncology. Although improvements are needed to increase tractability and accessibility while faithfully simulating the in vivo microenvironment, these models are powerful experimental platforms for understanding cancer biology, furthering drug screening, and facilitating development of therapeutics.

/pdf/engineered-models-to-parse-apart-the-metastatic-cascade-5p6tz4xear.pdf

Engineered models to parse apart the metastatic cascade

Brain metastasization of breast cancer

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.

Biofabrication Strategies and Engineered In Vitro Systems for Vascular Mechanobiology.

The cornea and the skin are two organs that form the outer barrier of the human body. When either is injured (e.g., from surgery, physical trauma, or chemical burns), wound healing is initiated to restore integrity. Many cells are activated during wound healing. In particular, fibroblasts that are stimulated often transition into repair fibroblasts or myofibroblasts that synthesize extracellular matrix (ECM) components into the wound area. Control of wound ECM deposition is critical, as a disorganized ECM can block restoration of function. One of the most abundant structural proteins in the mammalian ECM is collagen. Collagen type I is the main component in connective tissues. It can be readily obtained and purified, and short analogs have also been developed for tissue engineering applications, including modulating the wound healing response. This review discusses the effect of several current collagen implants on the stimulation of corneal and skin wound healing. These range from collagen sponges and hydrogels to films and membranes.

/pdf/collagen-as-a-biomaterial-for-skin-and-corneal-wound-healing-2np8tied.pdf

Collagen as a Biomaterial for Skin and Corneal Wound Healing

Long microchannels with thin walls, small width, and nanoholes or irregular shaped microgaps, which are similar to capillaries or cancerous vessels, are urgently needed to simulate the physiological activities in human body. However, the fabrication of such channels remains challenging. Here, microchannels with designable holes are manufactured by combining laser printing with line-contact capillary-force assembly. Two microwalls are first printed by femtosecond laser direct-writing, and subsequently driven to collapse into a channel by the capillary force that arises in the evaporation of developer. The channel can remain stable in solvent due to the enhanced Van der Waals' force caused by the line-contact of microwalls. Microchannels with controllable nanoholes and almost arbitrary patterns can be fabricated without any bonding or multistep processes. As-prepared microchannels, with wall thicknesses less than 1 µm, widths less than 3 µm, lengths more than 1 mm, are comparable with human capillaries. In addition, the prepared channels also exhibit the ability to steer the flow of liquid without any external pump.

Self-Sealed Bionic Long Microchannels with Thin Walls and Designable Nanoholes Prepared by Line-Contact Capillary-Force Assembly

Capillaries pervade human physiology. The mean intercapillary distance is only about 100 μm in human tissue, which indicates the extent of nutrient diffusion. In engineered tissue the lack of capillaries, along with the associated perfusion, is problematic because it leads to hypoxic stress and necrosis. However, a capillary is not easy to engineer due to its complex cytoarchitecture. Here, it is shown that it is possible to create in vitro, in about 30 min, a tubular microenvironment with an elastic modulus and porosity consistent with human tissue that functionally mimicks a bona fide capillary using "live cell lithography"(LCL) to control the type and position of cells on a composite hydrogel scaffold. Furthermore, it is established that these constructs support the forces associated with blood flow, and produce nutrient gradients similar to those measured in vivo. With LCL, capillaries can be constructed with single cell precision-no other method for tissue engineering offers such precision. Since the time required for assembly scales with the number of cells, this method is likely to be adapted first to create minimal functional units of human tissue that constitute organs, consisting of a heterogeneous population of 100-1000 cells, organized hierarchically to express a predictable function.

/pdf/synthetic-capillaries-to-control-microscopic-blood-flow-fcvn4k861d.pdf

Synthetic Capillaries to Control Microscopic Blood Flow

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Synthetic Capillaries to Control Microscopic Blood Flow