Science for humanity.

This year marks the 175th anniversary of the American Association for the Advancement of Science (AAAS, the publisher of Science). In striving to advance its mission, the organization's theme for its annual meeting (2 to 5 March in Washington, DC), "Science for Humanity," reiterates its commitment to explore and make sense of the world through inquiry, evidence seeking, and discovery. The words of archbishop and Nobel laureate Desmond Tutu are a reminder that this pursuit must be shared by everyone if it is to serve all of society: "My humanity is bound up in yours, for we can only be human together." These words aptly capture the essence of the ties that bind us, which include our shared DNA, our need to bond with others, and our ability to collaborate. Science is intertwined with the human condition and stories of the human experience and is hence the great connector. The more we embrace our common humanity-and science as a unifier-the better we will understand what it means to be human and what it will take to sustain ourselves and our planet.

Electric-field facilitated rapid and efficient dissociation of tissues Into viable single cells.

Single-Cell Analysis is a growing field that endeavors to obtain genetic profiles of individual cells. Disruption of cell-cell junctions and digestion of extracellular matrix in tissues requires tissue-specific mechanical and chemical dissociation protocols. Here, a new approach for dissociating tissues into constituent cells is described. Placing a tissue biopsy core within a liquid-filled cavity and applying an electric field between two parallel plate electrodes facilitates rapid dissociation of complex tissues into single cells. Different solution compositions, electric field strengths, and oscillation frequencies are investigated experimentally and with COMSOL Multiphysics. The method is compared with standard chemical and mechanical approaches for tissue dissociation. Treatment of tissue samples at 100 V/cm 1 kHz facilitated dissociation of 95 ± 4% of biopsy tissue sections in as little as 5 min, threefold faster than conventional chemical-mechanical techniques. The approach affords good dissociation of tissues into single cells while preserving cell viability, morphology, and cell cycle progression, suggesting utility for sample preparation of tissue specimens for direct Single-Cell Analysis.

Women in Medical Physics and Biomedical Engineering: past, present and future.

Women in Medical Physics and Biomedical Engineering (WiMPBME) is a Task Group established in 2014 under the International Union of Physical and Engineering Scientists in Medicine (IUPESM). The group's main role is to identify, develop, implement, and coordinate various tasks and projects related to women's needs and roles in medical physics and biomedical engineering around the world. The current paper summarizes the past, present and future goals and activities undertaken or planned by the Task group in order to motivate, nurture and support women in medical physics and biomedical engineering throughout their professional careers. In addition, the article includes the historical pathway followed by various women's groups and subcommittees from 2004 up to the present day and depicts future aims to further these professions in a gender-balanced manner.

The Biggest Challenges Resulting from the COVID-19 Pandemic on Gender-Related Work from Home in Biomedical Fields-World-Wide Qualitative Survey Analysis.

(1) Background: This paper aims to present and discuss the most significant challenges encountered by STEM professionals associated with remote working during the COVID-19 lockdowns. (2) Methods: We performed a qualitative analysis of 921 responses from professionals from 76 countries to the open-ended question: "What has been most challenging during the lockdown for you, and/or your family?" (3) Findings: Participants reported challenges within the immediate family to include responsibilities for school, childcare, and children's wellbeing; and the loss of social interactions with family and friends. Participants reported increased domestic duties, blurred lines between home and work, and long workdays. Finding adequate workspace was a problem, and adaptations were necessary, especially when adults shared the same setting for working and childcare. Connectivity issues and concentration difficulties emerged. While some participants reported employers' expectations did not change, others revealed concerns about efficiency. Mental health issues were expressed as anxiety and depression symptoms, exhaustion and burnout, and no outlets for stress. Fear of becoming infected with COVID-19 and uncertainties about the future also emerged. Pressure points related to gender, relationship status, and ethnicities were also evaluated. Public policies differed substantially across countries, raising concerns about the adherence to unnecessary restrictions, and similarly, restrictions being not tight enough. Beyond challenges, some benefits emerged, such as increased productivity and less time spent getting ready for work and commuting. Confinement resulted in more quality time and stronger relationships with family. (4) Interpretation: Viewpoints on positive and negative aspects of remote working differed by gender. Females were more affected professionally, socially, and personally than males. Mental stress and the feeling of inadequate work efficiency in women were caused by employers' expectations and lack of flexibility. Working from home turned out to be challenging, primarily due to a lack of preparedness, limited access to a dedicated home-office, and lack of previous experience in multi-layer/multi-scale environments.

Inequality in science and the case for a new agenda.

The history of the scientific enterprise demonstrates that it has supported gender, identity, and racial inequity. Further, its institutions have allowed discrimination, harassment, and personal harm of racialized persons and women. This has resulted in a suboptimal and demographically narrow research and innovation system, a concomitant limited lens on research agendas, and less effective knowledge translation between science and society. We argue that, to reverse this situation, the scientific community must reexamine its values and then collectively embark upon a moonshot-level new agenda for equity. This new agenda should be based upon the foundational value that scientific research and technological innovation should be prefaced upon progress toward a better world for all of society and that the process of how we conduct research is just as important as the results of research. Such an agenda will attract individuals who have been historically excluded from participation in science, but we will need to engage in substantial work to overcome the longstanding obstacles to their full participation. We highlight the need to implement this new agenda via a coordinated systems approach, recognizing the mutually reinforcing feedback dynamics among all science system components and aligning our equity efforts across them.

The impact of COVID-19 pandemic on gender-related work from home in STEM fields-Report of the WiMPBME Task Group.

The COVID-19 pandemic has forced many people, including those in the fields of science and engineering, to work from home. The new working environment caused by the pandemic is assumed to have a different impact on the amount of work that women and men can do from home. Particularly, if the major burden of child and other types of care is still predominantly on the shoulders of women. As such, a survey was conducted to assess the main issues that biomedical engineers, medical physicists (academics and professionals), and other similar professionals have been facing when working from home during the pandemic. A survey was created and disseminated worldwide. It originated from a committee of International Union for Physical and Engineering Sciences in Medicine (IUPESM; Women in Medical Physics and Biomedical Engineering Task Group) and supported by the Union. The ethics clearance was received from Carleton University. The survey was deployed on the Survey Monkey platform and the results were analyzed using IBM SPSS software. The analyses mainly consisted of frequency of the demographic parameters and the cross-tabulation of gender with all relevant variables describing the impact of work at home. A total of 921 responses from biomedical professions in 76 countries were received: 339 males, 573 females, and nine prefer-not-to-say/other. Regarding marital/partnership status, 85% of males were married or in partnership, and 15% were single, whereas 72% of females were married or in partnership, and 26% were single. More women were working from home during the pandemic (68%) versus 50% of men. More men had access to an office at home (68%) versus 64% for women. The proportion of men spending more than 3 h on child care and schooling per day was 12%, while for women it was 22%; for household duties, 8% of men spent more than 3 h; for women, this was 12.5%. It is interesting to note that 44% of men spent between 1 and 3 h per day on household duties, while for women, it was 55%. The high number of survey responses can be considered excellent. It is interesting to note that men participate in childcare and household duties in a relatively high percentage; although this corresponds to less hours daily than for women. It is far more than can be found 2 and 3 decades ago. This may reflect the situation in the developed countries only-as majority of responses (75%) was received from these countries. It is evident that the burden of childcare and household duties will have a negative impact on the careers of women if the burden is not more similar for both sexes. It is important to recognize that a change in policies of organizations that hire them may be required to provide accommodation and compensation to minimize the negative impact on the professional status and career of men and women who work in STEM fields.

Engineering Solutions to COVID-19 and Racial and Ethnic Health Disparities.

The role of engineers in response to the COVID-19 pandemic and in the elimination of health disparities, while not always visible, has important implications for the attainment of impactful solutions. The design skills, systems approach, and innovative mindset that engineers bring all have the potential to combat crises in novel and impactful ways. When a disparities lens is applied, a lens that views gaps in access, resources, and care, the engineering solutions are bound to be more robust and equitable. The disproportionate impact of COVID-19 on the Black community and other communities of color is linked to inequities in health rooted in a centuries long structural racism. Engineers working collaboratively with physicians and healthcare providers are poised to close equity gaps and strengthen the collective response to COVID-19 and future pandemics.

In Vitro Evaluation of the Influence of Substrate Mechanics on Matrix-Assisted Human Chondrocyte Transplantation.

Matrix-assisted chondrocyte transplantation (MACT) is of great interest for the treatment of patients with cartilage lesions. However, the roles of the matrix properties in modulating cartilage tissue integration during MACT recovery have not been fully understood. The objective of this study was to uncover the effects of substrate mechanics on the integration of implanted chondrocyte-laden hydrogels with native cartilage tissues. To this end, agarose hydrogels with Young's moduli ranging from 0.49 kPa (0.5%, w/v) to 23.08 kPa (10%) were prepared and incorporated into an in vitro human cartilage explant model. The hydrogel-cartilage composites were cultivated for up to 12 weeks and harvested for evaluation via scanning electron microscopy, histology, and a push-through test. Our results demonstrated that integration strength at the hydrogel-cartilage interface in the 1.0% (0.93 kPa) and 2.5% (3.30 kPa) agarose groups significantly increased over time, whereas hydrogels with higher stiffness (>8.78 kPa) led to poor integration with articular cartilage. Extensive sprouting of extracellular matrix in the interfacial regions was only observed in the 0.5% to 2.5% agarose groups. Collectively, our findings suggest that while neocartilage development and its integration with native cartilage are modulated by substrate elasticity, an optimal Young's modulus (3.30 kPa) possessed by agarose hydrogels is identified such that superior quality of tissue integration is achieved without compromising tissue properties of implanted constructs.

Solutions to Gender Balance in STEM Fields Through Support, Training, Education and Mentoring: Report of the International Women in Medical Physics and Biomedical Engineering Task Group.

The aim of this article is to offer a view of the current status of women in medical physics and biomedical engineering, while focusing on solutions towards gender balance and providing examples of current activities carried out at national and international levels. The International Union of Physical and Engineering Scientists in Medicine is committed to advancing women in science and health and has several initiatives overseen by the Women in Medical Physics and Biomedical Engineering Task Group. Some of the main strategies proposed by the Task Group to attain gender balance are: (a) identify and promote female role models that achieve successful work-life balance, (b) establish programs to develop female leaders, (c) create opportunities for females to increase the international visibility within the scientific community, and (d) establish archives and databases of women in STEM.

Adipogenic and Osteogenic Differentiation of In Vitro Aged Human Mesenchymal Stem Cells.

Multipotent mesenchymal stem cells (MSCs) are an attractive candidate for regeneration of damaged cells, tissues, and organs. Due to limited availabilities, MSC populations must be rapidly expanded to satisfy clinical needs. However, senescence attributed to extensive in vitro expansion compromises the regenerative and therapeutic potential of MSCs. In this chapter, we describe a step-by-step protocol that aims to induce adipogenic and osteogenic differentiation of in vitro aged human MSCs and highlight noteworthy issues that may arise during the process.

Changes in phenotype and differentiation potential of human mesenchymal stem cells aging in vitro.

BACKGROUND: Adult mesenchymal stem cells (MSCs) hold great promise for regenerative medicine because of their self-renewal, multipotency, and trophic and immunosuppressive effects. Due to the rareness and high heterogeneity of freshly isolated MSCs, extensive in-vitro passage is required to expand their populations prior to clinical use; however, senescence usually accompanies and can potentially affect MSC characteristics and functionality. Therefore, a thorough characterization of the variations in phenotype and differentiation potential of in-vitro aging MSCs must be sought. METHODS: Human bone marrow-derived MSCs were passaged in vitro and cultivated with either DMEM-based or αMEM-based expansion media. Cells were prepared for subculture every 10 days up to passage 8 and were analyzed for cell morphology, proliferative capacity, and surface marker expression at the end of each passage. The gene expression profile and adipogenic and osteogenic differentiation capability of MSCs at early (passage 4) and late (passage 8) passages were also evaluated. RESULTS: In-vitro aging MSCs gradually lost the typical fibroblast-like spindle shape, leading to elevated morphological abnormality and inhomogeneity. While the DMEM-based expansion medium better facilitated MSC proliferation in the early passages, the cell population doubling rate reduced over time in both DMEM and αMEM groups. CD146 expression decreased with increasing passage number only when MSCs were cultured under the DMEM-based condition. Senescence also resulted in MSCs with genetic instability, which was further regulated by the medium recipe. Regardless of the expansion condition, MSCs at both passages 4 and 8 could differentiate into adipocyte-like cells whereas osteogenesis of aged MSCs was significantly compromised. For osteogenic induction, use of the αMEM-based expansion medium yielded longer osteogenesis and better quality. CONCLUSIONS: Human MSCs subjected to extensive in-vitro passage can undergo morphological, phenotypic, and genetic changes. These properties are also modulated by the medium composition employed to expand the cell populations. In addition, adipogenic potential may be better preserved over osteogenesis in aged MSCs, suggesting that MSCs at early passages must be used for osteogenic differentiation. The current study presents valuable information for future basic science research and clinical applications leading to the development of novel MSC-based therapeutic strategies for different diseases.

Internal Viscosity-Dependent Margination of Red Blood Cells in Microfluidic Channels.

Cytoplasmic viscosity-dependent margination of red blood cells (RBC) for flow inside microchannels was studied using numerical simulations, and the results were verified with microfluidic experiments. Wide range of suspension volume fractions or hematocrits was considered in this study. Lattice Boltzmann method for fluid-phase coupled with spectrin-link method for RBC membrane deformation was used for accurate analysis of cell margination. RBC margination behavior shows strong dependence on the internal viscosity of the RBCs. At equilibrium, RBCs with higher internal viscosity marginate closer to the channel wall and the RBCs with normal internal viscosity migrate to the central core of the channel. Same margination pattern has been verified through experiments conducted with straight channel microfluidic devices. Segregation between RBCs of different internal viscosity is enhanced as the shear rate and the hematocrit increases. Stronger separation between normal RBCs and RBCs with high internal viscosity is obtained as the width of a high aspect ratio channel is reduced. Overall, the margination behavior of RBCs with different internal viscosities resembles with the margination behavior of RBCs with different levels of deformability. Observations from this work will be useful in designing microfluidic devices for separating the subpopulations of RBCs with different levels of deformability that appear in many hematologic diseases such as sickle cell disease (SCD), malaria, or cancer.

Cultivation of agarose-based microfluidic hydrogel promotes the development of large, full-thickness, tissue-engineered articular cartilage constructs.

The fabrication of tissue-engineered constructs of clinically relevant sizes continues to be plagued by poor nutrient transport to the interior of the construct. Consequences of poor mass transfer to the construct core include large gradients in cell viability and matrix deposition, as well as inadequate mechanical functionality. Prior literature has shown that embedded microfluidic channels offer the potential to control the spatial and temporal presentation of hydrodynamic and chemical cues within the developing tissue construct toward improved mass transfer. The current state of the art in microfluidic constructs, however, has fallen short of achieving sufficient thickness and robustness of constructs for further development towards translation. Towards this goal, we designed a microfluidic tissue construct and established bioprocessing conditions to meet nutrient transport requirements of a large, full-thickness, articular cartilage construct over a 2 week culture period. Our microfluidic constructs of 2.5 and 5 mm thicknesses showed enhanced cell proliferation relative to statically cultured constructs. These constructs, which are both thick and robust to culture periods of sufficient length to support extracellular matrix development, represent an important improvement over previously reported constructs which were thinner and lacking in extracellular matrix (most likely attributable to too-short culture periods). Copyright © 2014 John Wiley & Sons, Ltd.

Spatial Engineering of Osteochondral Tissue Constructs Through Microfluidically Directed Differentiation of Mesenchymal Stem Cells.

The development of tissue engineered osteochondral units has been slowed by a number of technical hurdles associated with recapitulating their heterogeneous nature ex vivo. Subsequently, numerous approaches with respect to cell sourcing, scaffolding composition, and culture media formulation have been pursued, which have led to high variability in outcomes and ultimately the lack of a consensus bioprocessing strategy. As such, the objective of this study was to standardize the design process by focusing on differentially supporting formation of cartilaginous and bony matrix by a single cell source in a spatially controlled manner within a single material system. A cell-polymer solution of bovine mesenchymal stem cells and agarose was cast against micromolds of a serpentine network and stacked to produce tissue constructs containing two independent microfluidic networks. Constructs were fluidically connected to two controlled flow loops and supplied with independently tuned differentiation parameters for chondrogenic and osteogenic induction, respectively. Constructs receiving inductive media showed differential gene expression of both chondrogenic and osteogenic markers in opposite directions along the thickness of the construct that was recapitulated at the protein level with respect to collagens I, II, and X. A control group receiving noninductive media showed homogeneous expression of these biomarkers measured in lower concentrations at both the mRNA and protein level. This work represents an important step in the rational design of engineered osteochondral units through establishment of an enabling technology for further optimization of scaffolding formulations and bioprocessing conditions toward the production of commercially viable osteochondral tissue products.