Wielding the Double-Edged Sword of Inflammation: Building Biomaterial-Based Strategies for Immunomodulation in Ischemic Stroke Treatment

Stroke is a leading cause of disability with no current treatment to regenerate lost brain tissue. Innovative preclinical and clinical trials have attempted to improve stroke recovery by promoting cell survival, downregulating astrogliosis and inflammation, and improving neurogenesis and angiogenesis; however, the complexity of stroke pathophysiology raises many challenges. Previous attempts to grossly inhibit the inflammatory reaction failed to improve stroke outcomes, prompting scientists to explore selective modulation rather than unbiased inhibition. Although experimental studies involving immunomodulation are successful, strategies have largely failed in the clinic. Some of these approaches are hindered by poor delivery efficiency or cell survival, challenges that could be at least partially overcome using biomaterials. Biomaterials may enhance immunomodulatory processes by improving drug and cell delivery to the injured tissue. Furthermore, the materials themselves can support healing and may be designed to act as immunomodulators, thereby contributing to tissue regeneration and endogenous repair processes. Described here are novel biomaterial-based strategies to modulate the immune response after ischemic stroke, with an emphasis on extracellular matrix mimetics and hydrogels for local delivery of drugs and cells. Finally, a future perspective is described, highlighting the potential of these therapies to achieve clinical translation and improve patients’ functional repair.     

Assembling Living Building Blocks to Engineer Complex Tissues

The great demand for tissue and organ grafts, compounded by an aging demographic and a shortage of available donors, has driven the development of bioengineering approaches that can generate biomimetic tissues in vitro. Despite the considerable progress in conventional scaffold‐based tissue engineering, the recreation of physiological complexity has remained a challenge. Bottom‐up tissue engineering strategies have opened up a new avenue for the modular assembly of living building blocks into customized tissue architectures. This Progress Report overviews the recent progress and trends in the fabrication and assembly of living building blocks, with a key highlight on emerging bioprinting technologies that can be used for modular assembly and complexity in tissue engineering. By summarizing the work to date, providing new classifications of different living building blocks, highlighting state‐of‐the‐art research and trends, and offering personal perspectives on future opportunities, this Progress Report aims to aid and inspire other researchers working in the field of modular tissue engineering.     

Can fermentation be used as a sustainable strategy to reduce iron and zinc binders in traditional African fermented cereal porridges or gruels?

Many weaning and complementary foods in Africa are plant based and thus are not good sources of bioavailable iron and zinc owing to the presence of anti-nutritional factors, in particular phytic acid, phenolic compounds, and, to some extent, dietary fiber. Several strategies are being developed to increase the levels of bioavailable iron and zinc in plant-based diets. These strategies range from fortification, biofortification, dietary diversification, and use of household processing methods such as soaking, cooking, germination, and fermentation. Fermentation poses a great potential as a significant amount of these foods in Africa involve a natural fermentation step. Exploration of this process could offer a more economical and sustainable way to reduce iron and zinc binders and consequently increase the bioavailability of the minerals in diets consisting of fermented cereals.     

Neochloris oleoabundans grown on anaerobically digested dairy manure for concomitant nutrient removal and biodiesel feedstock production

Microalgae have been investigated as a promising biodiesel feedstock; however, large-scale production is not currently cost-competitive with petroleum diesel, and its environmental impacts have received little attention. Using wastewater to supply nutrients for algal growth obviates synthetic fertilizer use, provides on-site nutrient removal, and reduces greenhouse gas emissions. In this work, anaerobically digested dairy manure was used to grow the oleaginous green alga Neochloris oleoabundans. In batch culture experiments with both synthetic media and anaerobic digester effluent, N. oleoabundans assimilated 90-95% of the initial nitrate and ammonium after 6 d and yielded 10-30% fatty acid methyl esters on a dry weight basis. Cellular lipid content and the N concentration in the growth media were inversely correlated. In addition, the proportion of polyunsaturated fatty acids (i.e. C16:3, C18:2, and C18:3) decreased with N concentration over time while the proportion of C18:1 fatty acid increased. Although N deficiency is likely the primary driver behind lipid accumulation, the influence of culture pH confounded results and requires further study. Other living microorganisms in the digester effluent were not observed to affect algal growth and lipid productivity, though the breakdown of organic nitrogen may have hindered lipid accumulation traditionally achieved through the manipulation of synthetic media. This work highlights the potential for waste-grown mono-algal cultures to produce high quality biodiesel while accomplishing simultaneous wastewater treatment.     

Continuous Action Reinforcement Learning for Control-Affine Systems with Unknown Dynamics

Control of nonlinear systems is challenging in realtime. Decision making, performed many times per second, must ensure system safety. Designing input to perform a task often involves solving a nonlinear system of differential equations, which is a computationally intensive, if not intractable problem. This article proposes sampling-based task learning for controlaffine nonlinear systems through the combined learning of both state and action-value functions in a model-free approximate value iteration setting with continuous inputs. A quadratic negative definite state-value function implies the existence of a unique maximum of the action-value function at any state. This allows the replacement of the standard greedy policy with a computationally efficient policy approximation that guarantees progression to a goal state without knowledge of the system dynamics. The policy approximation is consistent, i.e., it does not depend on the action samples used to calculate it. This method is appropriate for mechanical systems with high-dimensional input spaces and unknown dynamics performing Constraint-Balancing Tasks. We verify it both in simulation and experimentally for an Unmanned Aerial Vehicles (UAVs) carrying a suspended load, and in simulation, for the rendezvous of heterogeneous robots.      

Moving Beyond the Keg Party: A Daily Process Study of College Student Drinking Motivations.

Theoretical models of alcohol consumption assert that young adults endorse multiple drinking motives, including drinking to cope with negative experiences and to enhance positive experiences. Social contacts may be important to both pathways. This study applied daily process methodology to determine the relationship between college student drinking in different contexts and daily social contacts and moods. Each afternoon for 3 weeks, 122 undergraduates (43% men, 57% women) logged onto a secure Web site during specified hours to report daily activities, moods, and contacts. Hierarchical linear modeling analyses provided support for motivational models and the context-specific nature of motivated drinking. Individual differences were revealed for each motivation. These findings highlight the importance of studying within-person processes using daily process designs. (PsycINFO Database Record (c) 2010 APA, all rights reserved)