Carbodiimide-Driven Toughening of Interpenetrated Polymer Networks.

Recent work has demonstrated that temporary crosslinks in polymer networks generated by chemical "fuels" afford materials with large, transient changes in their mechanical properties. This can be accomplished in carboxylic-acid-functionalized polymer hydrogels using carbodiimides, which generate anhydride crosslinks with lifetimes on the order of minutes to hours. Here, the impact of the polymer network architecture on the mechanical properties of transiently crosslinked materials was explored. Single networks (SNs) were compared to interpenetrated networks (IPNs). Notably, semi-IPN precursors that give IPNs on treatment with carbodiimide give much higher fracture energies (i.e., resistance to fracture) and superior resistance to compressive strain compared to other network architectures. A precursor semi-IPN material featuring acrylic acid in only the free polymer chains yields, on treatment with carbodiimide, an IPN with a fracture energy of 2400 J/m2, a fourfold increase compared to an analogous semi-IPN precursor that yields a SN. This resistance to fracture enables the formation of macroscopic complex cut patterns, even at high strain, underscoring the pivotal role of polymer architecture in mechanical performance.

Silky Liquid Metal Electrodes for On-Skin Health Monitoring.

Next generation on-skin electrodes will require soft, flexible, and gentle materials to provide both high-fidelity sensing and wearer comfort. However, many commercially available on-skin electrodes lack these key properties due to their use of rigid hardware, harsh adhesives, uncomfortable support structures, and poor breathability. To address these challenges, this work presents a new device paradigm by joining biocompatible electrospun spider silk with printable liquid metal to yield an incredibly soft and scalable on-skin electrode that is strain-tolerant, conformable, and gentle on-skin. These electrodes, termed silky liquid metal (SLiM) electrodes, are found to be over five times more breathable than commercial wet electrodes, while the silk's intrinsic adhesion mechanism allows SLiM electrodes to avoid the use of harsh artificial adhesives, potentially decreasing skin irritation and inflammation over long-term use. Finally, the SLiM electrodes provide comparable impedances to traditional wet and other liquid metal electrodes, offering a high-fidelity sensing alternative with increased wearer comfort. Human subject testing confirmed the SLiM electrodes ability to sense electrophysiological signals with high fidelity and minimal irritation to the skin. The unique properties of the reported SLiM electrodes offer a comfortable electrophysiological sensing solution especially for patients with pre-existing skin conditions or surface wounds.

Forced labour risk is pervasive in the US land-based food supply.

Social risk assessments and case studies of labour conditions in food production primarily focus on specific subpopulations, regions and commodities. To date, research has not systematically assessed labour conditions against international standards across diverse, complex food products. Here we combine data on production, trade, labour intensity and qualitative risk coding to quantitatively assess the risk of forced labour embedded in the US land-based food supply, building on our previous assessment of fruits and vegetables. We demonstrate that animal-based proteins, processed fruits and vegetables, and discretionary foods are major contributors to forced labour risk and that 62% of total forced labour risk stems from domestic production or processing. Our findings reveal the widespread risk of forced labour present in the US food supply and the necessity of collaborative action across all countries-high, middle and low income-to eliminate reliance on labour exploitation.

Measurement of diets that are healthy, environmentally sustainable, affordable, and equitable: A scoping review of metrics, findings, and research gaps.

Introduction: Research on the impacts of dietary patterns on human and planetary health is a rapidly growing field. A wide range of metrics, datasets, and analytical techniques has been used to explore the role of dietary choices/constraints in driving greenhouse gas (GHG) emissions, environmental degradation, health and disease outcomes, and the affordability of food baskets. Many argue that each domain is important, but few have tackled all simultaneously in analyzing diet-outcome relationships. Methods: This paper reviews studies published between January 2015 and December 2021 (inclusive) that examined dietary patterns in relation to at least two of the following four thematic pillars: (i) planetary health, including, climate change, environmental quality, and natural resource impacts, (ii) human health and disease, (iii) economic outcomes, including diet cost/affordability, and (iv) social outcomes, e.g., wages, working conditions, and culturally relevant diets. We systematically screened 2,425 publications by title and abstract and included data from 42 eligible publications in this review. Results: Most dietary patterns used were statistically estimated or simulated rather than observed. A rising number of studies consider the cost/affordability of dietary scenarios in relation to optimized environmental and health outcomes. However, only six publications incorporate social sustainability outcomes, which represents an under-explored dimension of food system concerns. Discussion: This review suggests a need for (i) transparency and clarity in datasets used and analytical methods; (ii) explicit integration of indicators and metrics linking social and economic issues to the commonly assessed diet-climate-planetary ecology relationships; (iii) inclusion of data and researchers from low- and middle-income countries; (iv) inclusion of processed food products to reflect the reality of consumer choices globally; and (v) attention to the implications of findings for policymakers. Better understanding is urgently needed on dietary impacts on all relevant human and planetary domains simultaneously.

Chemically Fueled Reinforcement of Polymer Hydrogels.

Carbodiimide-fueled anhydride bond formation has been used to enhance the mechanical properties of permanently crosslinked polymer networks, giving materials that exhibit transitions from soft gels to covalently reinforced gels, eventually returning to the original soft gels. Temporary changes in mechanical properties result from a transient network of anhydride crosslinks, which eventually dissipate by hydrolysis. Over an order of magnitude increase in the storage modulus is possible through carbodiimide fueling. The time-dependent mechanical properties can be modulated by the concentration of carbodiimide, temperature, and primary chain architecture. Because the materials remain rheological solids, new material functions such as temporally controlled adhesion and rewritable spatial patterns of mechanical properties have been realized.

Extrusion 3D printing of keratin protein hydrogels free of exogenous chemical agents.

Keratins are a class of intermediate filament proteins that can be obtained from numerous sources including human hair. Materials fabricated from keratins offer desirable characteristics as scaffolds for tissue engineering, including intrinsic cell adhesion sequences and tunable degradation kinetics. The capacity to create 3D printed constructs from keratin-based bio-inks generates unique opportunities for spatial control of scaffold physicochemical properties to direct scaffold functions in ways not readily achieved through other means. The aim of this study was to leverage the controllable rheological properties of keratin hydrogels to create a strategy for extrusion 3D printing of keratin bio-inks without the use of exogenous rheological modifiers, crosslinking agents, or photocurable resins. The rheological properties of keratin hydrogels were tuned by varying two parameters: (a) the ratio of keratose (obtained by oxidative extraction of keratin) to kerateine (obtained by reductive extraction of keratin); and (b) the weight percentage of total keratin protein in the gel. A computational model of the dispensing nozzle for a commercially available extrusion 3D printer was developed to calculate the needed pneumatic printing pressures based on the known rheological properties of the gels. Keratin hydrogel constructs, of varying keratose/kerateine ratios and total keratin weight percentages, were 3D printed in cylindrical geometries via extrusion 3D printing. Rheology and degradation studies showed that gels with greater relative kerateine content exhibited greater flow resistance and slower degradation kinetics when submerged in phosphate buffered saline solution at 37 °C, owing to the presence of cysteine residues in kerateine and the capability of forming disulfide bonds. Total keratin weight percentage was found to influence gel yield stress, with possible implications for tuning filament fidelity. Findings from this work support the use of keratose/kerateine ratio and total keratin weight percentage as handles for modulating rheological characteristics of keratin hydrogels to enhance printability and control scaffold properties.

Aromatic foldamers as molecular springs in network polymers.

Polymer networks crosslinked with spring-like ortho-phenylene (oP) foldamers were developed. NMR analysis indicated the oP crosslinkers were well-folded. Polymer networks with oP-based crosslinkers showed enhanced energy dissipation and elasticity compared to divinylbenzene crosslinked networks. The energy dissipation was attributed to the strain-induced reversible unfolding of the oP units. Energy dissipation increased with the number of helical turns in the foldamer.

Revealing global risks of labor abuse and illegal, unreported, and unregulated fishing.

Labor abuse on fishing vessels and illegal, unreported and unregulated (IUU) fishing violate human rights, jeopardize food security, and deprive governments of revenues. We applied a multi-method approach, combining new empirical data with satellite information on fishing activities and vessel characteristics to map risks of labor abuse and IUU fishing, understand their relationships, and identify major drivers. Port risks were globally pervasive and often coupled, with 57% of assessed ports associated with labor abuse or IUU fishing. For trips ending in assessed ports, 82% were linked to labor abuse or IUU fishing risks. At-sea risk areas were primarily driven by fishing vessel flags linked to poor control of corruption by the flag state, high ownership by countries other than the flag state, and Chinese-flagged vessels. Transshipment risk areas were related to the gear type of fishing vessels engaged in potential transshipment and carrier vessel flags. Measures at port offer promise for mitigating risks, through the Port State Measures Agreement for IUU fishing, and ensuring sufficient vessel time at port to detect and respond to labor abuse. Our results highlight the need for coordinated action across actors to avoid risk displacement and make progress towards eliminating these socially, environmentally and economically unsustainable practices.

3D-Printed Self-Healing Elastomers for Modular Soft Robotics.

Advances in materials, designs, and controls are propelling the field of soft robotics at an incredible rate; however, current methods for prototyping soft robots remain cumbersome and struggle to incorporate desirable geometric complexity. Herein, a vat photopolymerizable self-healing elastomer system capable of extreme elongations up to 1000% is presented. The material is formed from a combination of thiol/acrylate mixed chain/step-growth polymerizations and uses a combination of physical processes and dynamic-bond exchange via thioethers to achieve full self-healing capacity over multiple damage/healing cycles. These elastomers can be three dimensional (3D) printed with modular designs capable of healing together to form highly complex and large functional soft robots. Additionally, these materials show reprogrammable resting shapes and compatibility with self-healing liquid metal electronics. Using these capabilities, subcomponents with multiple internal channel systems were printed, healed together, and combined with functional liquid metals to form a high-wattage pneumatic switch and a humanoid-scale soft robotic gripper. The combination of 3D printing and self-healing elastomeric materials allows for facile production of support-free parts with extreme complexity, resulting in a paradigm shift for the construction of modular soft robotics.

Heat- and Light-Responsive Materials Through Pairing Dynamic Thiol-Michael and Coumarin Chemistry.

Covalent adaptable networks (CANs) based on the thiol-Michael (TM) linkages can be thermal and pH responsive. Here, a new vinyl-sulfone-based thiol-Michael crosslinker is synthesized and incorporated into acrylate-based CANs to achieve stable materials with dynamic properties. Because of the reversible TM linkages, excellent temperature-responsive re-healing and malleability properties are achieved. In addition, for the first time, a photoresponsive coumarin moiety is incorporated with TM-based CANs to introduce light-mediated reconfigureability and postpolymerization crosslinking. Overall, these materials can be on demand dynamic in response to heat and light but can retain mechanical stability at ambient condition.

Impact of tumor-parenchyma biomechanics on liver metastatic progression: a multi-model approach.

Colorectal cancer and other cancers often metastasize to the liver in later stages of the disease, contributing significantly to patient death. While the biomechanical properties of the liver parenchyma (normal liver tissue) are known to affect tumor cell behavior in primary and metastatic tumors, the role of these properties in driving or inhibiting metastatic inception remains poorly understood, as are the longer-term multicellular dynamics. This study adopts a multi-model approach to study the dynamics of tumor-parenchyma biomechanical interactions during metastatic seeding and growth. We employ a detailed poroviscoelastic model of a liver lobule to study how micrometastases disrupt flow and pressure on short time scales. Results from short-time simulations in detailed single hepatic lobules motivate constitutive relations and biological hypotheses for a minimal agent-based model of metastatic growth in centimeter-scale tissue over months-long time scales. After a parameter space investigation, we find that the balance of basic tumor-parenchyma biomechanical interactions on shorter time scales (adhesion, repulsion, and elastic tissue deformation over minutes) and longer time scales (plastic tissue relaxation over hours) can explain a broad range of behaviors of micrometastases, without the need for complex molecular-scale signaling. These interactions may arrest the growth of micrometastases in a dormant state and prevent newly arriving cancer cells from establishing successful metastatic foci. Moreover, the simulations indicate ways in which dormant tumors could "reawaken" after changes in parenchymal tissue mechanical properties, as may arise during aging or following acute liver illness or injury. We conclude that the proposed modeling approach yields insight into the role of tumor-parenchyma biomechanics in promoting liver metastatic growth, and advances the longer term goal of identifying conditions to clinically arrest and reverse the course of late-stage cancer.

Risk of forced labour embedded in the US fruit and vegetable supply.

Sustainable food consumption studies have largely focused on promoting human health within ecological limits. Less attention has been paid to social sustainability, in part because of limited data and models. Globally, agriculture has one of the highest incidences of forced labour, with exploitative conditions enabled by low margins, domestic labour scarcity, inadequate legal protections for workers and high labour requirements. Here we assess the forced labour risk embedded in the US retail supply of fruits and vegetables using distinct datasets and a new forced labour risk scoring method. We demonstrate that there is risk of forced labour in a broad set of fruit and vegetable commodities, with a small number of commodities accounting for a substantial fraction of total risk at the retail supply level. These findings signal potential trade-offs and synergies across dimensions of food system sustainability and the need for novel research approaches to develop evidence-based forced labour risk mitigation strategies.

Chemically fueled covalent crosslinking of polymer materials.

Transiently crosslinked dynamic polymer networks are developed, using carbodiimide hydration to link carboxylic acids as anhydrides. From aqueous polymer solutions, non-equilibrium hydrogels are transiently formed, which dissolve upon anhydride hydrolysis. The materials can be refueled using a subsequent injection of carbodiimide. The gels exhibit higher storage moduli compared to transient supramolecular gels as a result of their covalent crosslinks.

Anilinium Salts in Polymer Networks for Materials with Mechanical Stability and Mild Thermally Induced Dynamic Properties.

Dynamic nucleophilic exchange of quaternary anilinium salts has been incorporated into rehealable and malleable polymeric materials that can be activated under mild (60 °C) thermal stimulus. The mechanism of dynamic exchange between quaternary anilinium salt and free aniline was assessed in small-molecule model experiments. The dynamic exchange was found to be dissociative in nature, due to the indirect SN2 mechanism, where initially the bromide anion attacks the anilinium salt to generate an alkyl bromide which undergoes subsequent attack by a free aniline group. A quaternary anilinium-based cross-linker was synthesized to act as dynamic linkages in the polymer network. Cross-linked polymeric materials showed thermoresponsive rehealing and malleability properties at 60 °C along with being resistant to irreversible creep under ambient conditions. The use of anilinium salts enables dynamic exchange to occur with significantly milder thermal stimulus than other comparable materials, while maintaining mechanical stability.

Race and ethnicity are not primary determinants in utilizing veterinary services in underserved communities in the United States.

A retrospective database analysis (2011-2015) evaluated associations between race and ethnicity and veterinary service utilization by sampling 83,260 companion animals whose guardians (owners) self-identified as White, Black, or Latino/a from 39 Humane Society of the United States Pets for Life (PFL) sites across the United States. Controlling for socioeconomic status, the percentage of nonhuman animals sterilized through PFL whose owners were Latino/a or Black was substantially higher than in previously reported findings. While Latinos/as had the highest mean number of days from first contact with the program to consent, they also had the highest percentage of owners accepting the voucher during initial contact. Logistic regression models suggested that although meaningful, race and ethnicity were not primary determinants of veterinary service utilization. When veterinary and animal welfare organizations deliberately remove structural barriers embedded with racial inequalities, individuals, regardless of race and ethnicity, proceed with companion-animal sterilization. Therefore, service providers must use unbiased, informed, and culturally competent practices to improve companion-animal welfare through the optimization of veterinary services, including spay and neuter.

Shear stress upregulates regeneration-related immediate early genes in liver progenitors in 3D ECM-like microenvironments.

The role of fluid stresses in activating the hepatic stem/progenitor cell regenerative response is not well understood. This study hypothesized that immediate early genes (IEGs) with known links to liver regeneration will be upregulated in liver progenitor cells (LPCs) exposed to in vitro shear stresses on the order of those produced from elevated interstitial flow after partial hepatectomy. The objectives were: (1) to develop a shear flow chamber for application of fluid stress to LPCs in 3D culture; and (2) to determine the effects of fluid stress on IEG expression in LPCs. Two hours of shear stress exposure at ∼4 dyn/cm2 was applied to LPCs embedded individually or as 3D spheroids within a hyaluronic acid/collagen I hydrogel. Results were compared against static controls. Quantitative reverse transcriptase polymerase chain reaction was used to evaluate the effect of experimental treatments on gene expression. Twenty-nine genes were analyzed, including IEGs and other genes linked to liver regeneration. Four IEGs (CFOS, IP10, MKP1, ALB) and three other regeneration-related genes (WNT, VEGF, EpCAM) were significantly upregulated in LPCs in response to fluid mechanical stress. LPCs maintained an early to intermediate stage of differentiation in spheroid culture in the absence of the hydrogel, and addition of the gel initiated cholangiocyte differentiation programs which were abrogated by the onset of flow. Collectively the flow-upregulated genes fit the pattern of an LPC-mediated proliferative/regenerative response. These results suggest that fluid stresses are potentially important regulators of the LPC-mediated regeneration response in liver.

Association of a Surgical Task During Training With Team Skill Acquisition Among Surgical Residents: The Missing Piece in Multidisciplinary Team Training.

IMPORTANCE: The human patient simulators that are currently used in multidisciplinary operating room team training scenarios cannot simulate surgical tasks because they lack a realistic surgical anatomy. Thus, they eliminate the surgeon's primary task in the operating room. The surgical trainee is presented with a significant barrier when he or she attempts to suspend disbelief and engage in the scenario. OBJECTIVE: To develop and test a simulation-based operating room team training strategy that challenges the communication abilities and teamwork competencies of surgeons while they are engaged in realistic operative maneuvers. DESIGN, SETTING, AND PARTICIPANTS: This pre-post educational intervention pilot study compared the gains in teamwork skills for midlevel surgical residents at Wake Forest Baptist Medical Center after they participated in a standardized multidisciplinary team training scenario with 3 possible levels of surgical realism: (1) SimMan (Laerdal) (control group, no surgical anatomy); (2) "synthetic anatomy for surgical tasks" mannequin (medium-fidelity anatomy), and (3) a patient simulated by a deceased donor (high-fidelity anatomy). INTERVENTIONS: Participation in the simulation scenario and the subsequent debriefing. MAIN OUTCOMES AND MEASURES: Teamwork competency was assessed using several instruments with extensive validity evidence, including the Nontechnical Skills assessment, the Trauma Management Skills scoring system, the Crisis Resource Management checklist, and a self-efficacy survey instrument. Participant satisfaction was assessed with a Likert-scale questionnaire. RESULTS: Scenario participants included midlevel surgical residents, anesthesia providers, scrub nurses, and circulating nurses. Statistical models showed that surgical residents exposed to medium-fidelity simulation (synthetic anatomy for surgical tasks) team training scenarios demonstrated greater gains in teamwork skills compared with control groups (SimMan) (Nontechnical Skills video score: 95% CI, 1.06-16.41; Trauma Management Skills video score: 95% CI, 0.61-2.90) and equivalent gains in teamwork skills compared with high-fidelity simulations (deceased donor) (Nontechnical Skills video score: 95% CI, -8.51 to 6.71; Trauma Management Skills video score: 95% CI, -1.70 to 0.49). CONCLUSIONS AND RELEVANCE: Including a surgical task in operating room team training significantly enhanced the acquisition of teamwork skills among midlevel surgical residents. Incorporating relatively inexpensive, medium-fidelity synthetic anatomy in human patient simulators was as effective as using high-fidelity anatomies from deceased donors for promoting teamwork skills in this learning group.

3D printing of an interpenetrating network hydrogel material with tunable viscoelastic properties.

Interpenetrating network (IPN) hydrogel materials are recognized for their unique mechanical properties. While IPN elasticity and toughness properties have been explored in previous studies, the factors that impact the time-dependent stress relaxation behavior of IPN materials are not well understood. Time-dependent (i.e. viscoelastic) mechanical behavior is a critical design parameter in the development of materials for a variety of applications, such as medical simulation devices, flexible substrate materials, cellular mechanobiology substrates, or regenerative medicine applications. This study reports a novel technique for 3D printing alginate-polyacrylamide IPN gels with tunable elastic and viscoelastic properties. The viscoelastic stress relaxation behavior of the 3D printed alginate-polyacrylamide IPN hydrogels was influenced most strongly by varying the concentration of the acrylamide cross-linker (MBAA), while the elastic modulus was affected most by varying the concentration of total monomer material. The material properties of our 3D printed IPN constructs were consistent with those reported in the biomechanics literature for soft tissues such as skeletal muscle, cardiac muscle, skin and subcutaneous tissue.