Evaluation of Digitally Encoded Layer‐by‐layer Coated Microparticles as Cell Carriers

To obtain more biologically relevant data there is a growing interest in the use of living cells for assaying the biological activity of unknown chemical compounds. Density ‘multiplex’ cell‐based assays, where different cell types are mixed in one well and simultaneously investigated upon exposure to a certain compound are beginning to emerge. To be able to identify the cells they should be attached to microscopic carriers that are encoded. This paper investigates how digitally encoded microparticles can be loaded with cells while keeping the digital code in the microcarriers readable. It turns out that coating the surface of the encoded microcarriers with polyelectrolytes using the layer‐by‐layer (LbL) approach provides the microcarriers with a ‘highly functional’ surface. The polyelectrolyte layer allows the growth of the cells, allows the orientation of the cell loaded microcarriers in a magnetic field, and does not hamper the reading of the code. It has further been shown that the cells growing on the polyelectrolyte layer can become transduced by adenoviral particles hosted by the polyelectrolyte layer. It is concluded that the digitally encoded microparticles are promising materials for use in biomedical and pharmaceutical in‐vitro research where cells are used as tools.     

A New Microengineered Platform for 4D Tracking of Single Cells in a Stem-Cell-Based In Vitro Morphogenesis Model

Recently developed stem-cell-based in vitro models of morphogenesis can help shed light on the mechanisms involved in embryonic patterning. These models are showcased using traditional cell culture platforms and materials, which allow limited control over the biological system and usually do not support high-content imaging. In contrast, using advanced microengineered tools can help in microscale control, long-term culture, and real-time data acquisition from such biological models and aid in elucidating the underlying mechanisms. Here, a new culturing, manipulation and analysis platform is described to study in vitro morphogenesis using thin polycarbonate film-based microdevices. A pipeline consisting of open-source software to quantify 3D cell movement using 4D image acquisition is developed to analyze cell migration within the multicellular clusters. It is shown that the platform can be used to control and study morphogenesis in non-adherent cultures of the P19C5 mouse stem cell line and mouse embryonic stem cells (mESCs) that show symmetry breaking and axial elongation events similar to early embryonic development. Using the new platform, it is found that localized cell proliferation and coordinated cell migration result in elongation morphogenesis of the P19C5 aggregates. Further, it is found that polarization and elongation of mESC aggregates are dependent on directed cell migration.     

Grow with the Flow: When Morphogenesis Meets Microfluidics

Developmental biology has advanced the understanding of the intricate and dynamic processes involved in the formation of an organism from a single cell. However, many gaps remain in the knowledge of embryonic development, especially regarding tissue morphogenesis. A possible approach to mimic such phenomena uses pluripotent stem cells in in vitro morphogenetic models. Herein, these systems are summarized with emphasis on the ability to better manipulate and control cellular interfaces with either liquid or solid materials using microengineered tools, which is critical for attaining deeper insights into pattern formation and stem cell differentiation during organogenesis. The role of conventional and customized cell‐culture systems in supporting important advances in the field of morphogenesis is discussed, and the fascinating role that material sciences and microengineering currently play and are expected to play in the future is highlighted. In conclusion, it is proffered that continued microfluidics innovations when applied to morphogenesis promise to provide important insights to advance many multidisciplinary fields, including regenerative medicine.     

Surface Micro‐ and Nanoengineering: Applications of Layer‐by‐Layer Technology as a Versatile Tool to Control Cellular Behavior

Extracellular matrix (ECM) cues have been widely investigated for their impact on cellular behavior. Among mechanics, physics, chemistry, and topography, different ECM properties have been discovered as important parameters to modulate cell functions, activating mechanotransduction pathways that can influence gene expression, proliferation or even differentiation. Particularly, ECM topography has been gaining more and more interest based on the evidence that these physical cues can tailor cell behavior. Here, an overview of bottom‐up and top‐down approaches reported to produce materials capable of mimicking the ECM topography and being applied for biomedical purposes is provided. Moreover, the increasing motivation of using the layer‐by‐layer (LbL) technique to reproduce these topographical cues is highlighted. LbL assembly is a versatile methodology used to coat materials with a nanoscale fidelity to the geometry of the template or to produce multilayer thin films composed of polymers, proteins, colloids, or even cells. Different geometries, sizes, or shapes on surface topography can imply different behaviors: effects on the cell adhesion, proliferation, morphology, alignment, migration, gene expression, and even differentiation are considered. Finally, the importance of LbL assembly to produce defined topographical cues on materials is discussed, highlighting the potential of micro‐ and nanoengineered materials to modulate cell function and fate.     

An artificial elementary eye with optic flow detection and compositional properties

We describe a 2 mg artificial elementary eye whose structure and functionality is inspired by compound eye ommatidia. Its optical sensitivity and electronic architecture are sufficient to generate the required signals for the measurement of local optic flow vectors in multiple directions. Multiple elementary eyes can be assembled to create a compound vision system of desired shape and curvature spanning large fields of view. The system configurability is validated with the fabrication of a flexible linear array of artificial elementary eyes capable of extracting optic flow over multiple visual directions.     

Microengineering Pressure Sensor Active Layers for Improved Performance

Pressure sensors play an integral role in a wide range of applications, such as soft robotics and health monitoring. In order to meet this demand, many groups microengineer the active layer—the layer that deforms under pressure and dictates changes in the output signal—of capacitive, resistive/piezoresistive, piezoelectric, and triboelectric pressure sensors in order to improve sensor performance. Geometric microengineering of the active layer has been shown to improve performance parameters such as sensitivity, dynamic range, limit of detection, and response and relaxation times. There are a wide range of implemented designs, including microdomes, micropyramids, lines or microridges, papillae, microspheres, micropores, and microcylinders, each offering different advantages for a particular application. It is important to compare the techniques by which the microengineered active layers are designed and fabricated as they may provide additional insights on compatibility and sensing range limits. To evaluate each fabrication method, it is critical to take into account the active layer uniformity, ease of fabrication, shape and size versatility and tunability, and scalability of both the device and the fabrication process. By better understanding how microengineering techniques and design compares, pressure sensors can be targetedly designed and implemented.     

25th Anniversary Article: Rational Design and Applications of Hydrogels in Regenerative Medicine

Hydrogels are hydrophilic polymer‐based materials with high water content and physical characteristics that resemble the native extracellular matrix. Because of their remarkable properties, hydrogel systems are used for a wide range of biomedical applications, such as three‐dimensional (3D) matrices for tissue engineering, drug‐delivery vehicles, composite biomaterials, and as injectable fillers in minimally invasive surgeries. In addition, the rational design of hydrogels with controlled physical and biological properties can be used to modulate cellular functionality and tissue morphogenesis. Here, the development of advanced hydrogels with tunable physiochemical properties is highlighted, with particular emphasis on elastomeric, light‐sensitive, composite, and shape‐memory hydrogels. Emerging technologies developed over the past decade to control hydrogel architecture are also discussed and a number of potential applications and challenges in the utilization of hydrogels in regenerative medicine are reviewed. It is anticipated that the continued development of sophisticated hydrogels will result in clinical applications that will improve patient care and quality of life.