Summary Recent years have seen tremendous advances in the field of hydrogel-based biomaterials. One of the most prominent revolutions in this field has been the integration of elements or techniques that enable spatial and temporal control over hydrogels’ properties and functions. Here, we critically review the emerging progress of spatiotemporal control over biomaterial properties towards the development of functional engineered tissue constructs. Specifically, we will highlight the main advances in the spatial control of biomaterials, such as surface modification, microfabrication, photo-patterning, and three-dimensional (3D) bioprinting, as well as advances in the temporal control of biomaterials, such as controlled release of molecules, photocleaving of proteins, and controlled hydrogel degradation. We believe that the development and integration of these techniques will drive the engineering of next-generation engineered tissues.

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The ideal in vitro recreation of the micro-tumor niche—although much needed for a better understanding of cancer etiology and development of better anticancer therapies—is highly challenging. Tumors are complex three-dimensional (3D) tissues that establish a dynamic cross-talk with the surrounding tissues through complex chemical signaling. An extensive body of experimental evidence has established that 3D culture systems more closely recapitulate the architecture and the physiology of human solid tumors when compared with traditional 2D systems. Moreover, conventional 3D culture systems fail to recreate the dynamics of the tumor niche. Tumor-on-chip systems, which are microfluidic devices that aim to recreate relevant features of the tumor physiology, have recently emerged as powerful tools in cancer research. In tumor-on-chip systems, the use of microfluidics adds another dimension of physiological mimicry by allowing a continuous feed of nutrients (and pharmaceutical compounds). Here, we discuss recently published literature related to the culture of solid tumor-like tissues in microfluidic systems (tumor-on-chip devices). Our aim is to provide the readers with an overview of the state of the art on this particular theme and to illustrate the toolbox available today for engineering tumor-like structures (and their environments) in microfluidic devices. The suitability of tumor-on-chip devices is increasing in many areas of cancer research, including the study of the physiology of solid tumors, the screening of novel anticancer pharmaceutical compounds before resourcing to animal models, and the development of personalized treatments. In the years to come, additive manufacturing (3D bioprinting and 3D printing), computational fluid dynamics, and medium- to high-throughput omics will become powerful enablers of a new wave of more sophisticated and effective tumor-on-chip devices.

BackgroundThe Cancer Stem Cell (CSC) hypothesis has gained credibility within the cancer research community. According to this hypothesis, a small subpopulation of cells within cancerous tissues exhibits stem-cell-like characteristics and is responsible for the maintenance and proliferation of cancer.Methodologies/Principal FindingsWe present a simple compartmental pseudo-chemical mathematical model for tumor growth, based on the CSC hypothesis, and derived using a “chemical reaction” approach. We defined three cell subpopulations: CSCs, transit progenitor cells, and differentiated cells. Each event related to cell division, differentiation, or death is then modeled as a chemical reaction. The resulting set of ordinary differential equations was numerically integrated to describe the time evolution of each cell subpopulation and the overall tumor growth. The parameter space was explored to identify combinations of parameter values that produce biologically feasible and consistent scenarios.Conclusions/SignificanceCertain kinetic relationships apparently must be satisfied to sustain solid tumor growth and to maintain an approximate constant fraction of CSCs in the tumor lower than 0.01 (as experimentally observed): (a) the rate of symmetrical and asymmetrical CSC renewal must be in the same order of magnitude; (b) the intrinsic rate of renewal and differentiation of progenitor cells must be half an order of magnitude higher than the corresponding intrinsic rates for cancer stem cells; (c) the rates of apoptosis of the CSC, transit amplifying progenitor (P) cells, and terminally differentiated (D) cells must be progressively higher by approximately one order of magnitude. Simulation results were consistent with reports that have suggested that encouraging CSC differentiation could be an effective therapeutic strategy for fighting cancer in addition to selective killing or inhibition of symmetric division of CSCs.

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It is difficult to find a chemical production facility without a vessel agitated by some kind of impeller. The engineer's intuition, trained by several decades of industrial praxis, inclines him/her to select a stirred tank almost every time that the word mixing is mentioned in a chemical process context. As a result, stirred tanks are the most extensively used mixing devices in the chemical industries for both turbulent and laminar applications. However, their common use does not necessarily imply that we know how to design and operate them effectively.The traditional approach to mixing can be regarded with a touch of irony. Although our ultimate objective is to disorder a system, i.e., to randomize positions and to destroy initial segregation, we insist in achieving these objectives by means of symmetric systems and time-periodic protocols. Regarding stirred tanks, the most used impeller designs, namely the Rushton turbine, the four blade axial impeller, and the marine-type propellers are all centrally symmetric 1 . When several impellers are used, generally they are aligned and the distance between them is set constant. If baffles are used then an even number of them, once again, located symmetrically, is recommended. And, just to be on the safe side, concentric shaft configurations are overwhelmingly preferred. Moreover, the operational protocols are time-periodic (i.e., 300 rpm).There is a practical reason for this inclination to symmetry. Symmetric systems are mechanically more stable when operation is required in turbulent regime, and constant rpm protocols are easy to implement. However, it is known (see Lamberto et al., 1996) that symmetry induces serious mixing pathologies in stirred tanks when used for laminar applications (e.g., the existence of isolated regions of regular motion and flow separatrices). These mixing insufficiencies are caused by the structure of the global unstable manifolds, which for periodic/symmetric flows never fill the entire flow domain, due to the required existence of non-chaotic domains in such flows.A common approach to overcome these mixing problems has been to use complicated impeller geometries for low Re mixing (ribbon impellers, anchor impellers, etc.). Another strategy, suggested by Lamberto et al. (1996), was to use variable speed protocols to create the widespread chaos required to achieve effective mixing in the laminar regime. The substitution of constant rpm protocols for variable-speed ones can require retrofits and operation protocols that are in some cases both expensive and complicated. We would like to introduce the smallest possible modification and still be able to achieve major enhancement in mixing performance. In this communication we propose a different avenue to achieve globally chaotic conditions in stirred tanks: eccentricity.

This study is the first focused on the presence of SARS-CoV-2 in different freshwater environments in an urban setting. Groundwater and surface water reservoirs for drinking water as well as water from receiving rivers of the Monterrey Metropolitan Area were sampled repeatedly during a SARS-CoV-2 peak phase between October 2020 and January 2021, and viral RNA was measured by quantitative reverse transcription polymerase chain reaction. Forty-four percent of the groundwater samples had detectable viral loads between 2.6 and 38.3 copies/ml. A significant correlation between viral load and sucralose concentration in groundwater reaffirmed the hypothesis of leaching and infiltrating effluent from surface and/or failing sewage pipes and emphasized the importance of water disinfection. Twelve percent of the surface water dam samples tested positive for viral RNA, with values varying between 3.3 and 3.8 copies/ml. Finally, 13% of the river samples were positive for viral RNA, with concentrations ranging from 2.5 to 7.0 copies/ml. Untreated wastewater samples taken in the same period showed viral loads of up to 3535 copies/ml, demonstrating a dilution effect and/or wastewater facilities efficiency of three orders of magnitude. Variations in the viral loads in the groundwater and surface water over time and at the submetropolitan level generally reflected the reported trends in infection cases for Monterrey. The viral loads in the freshwater environments of Monterrey represent a low risk for recreational activities according to a preliminary risk assessment model. However, this result should not be taken lightly due to uncertainty regarding data and model constraints and the possibility of situations where the infection risk may increase considerably.

A novel extrusion bioprinting system capable of individually and/or simultaneously depositing multiple different materials through a digitally tunable pneumatic system is developed by Y. S. Zhang, A. Khademhosseini, and co‐workers as described in article 1604630. The integration of a single‐printhead setup eliminates the need of physical nozzle switches, allowing for rapid and continuous fabrication of multicomponent structures.