Imaging and plate counting to quantify the effect of an antimicrobial: A case study of a photo-activated chlorine dioxide treatment.

AIM: To assess removal versus kill efficacies of antimicrobial treatments against thick biofilms with statistical confidence. METHODS AND RESULTS: A photo-activated chlorine dioxide treatment (Photo ClO2 ) was tested in two independent experiments against thick (>100 µm) Pseudomonas aeruginosa biofilms. Kill efficacy was assessed by viable plate counts. Removal efficacy was assessed by 3D confocal scanning laser microscope imaging (CSLM). Biovolumes were calculated using an image analysis approach that models the penetration limitation of the laser into thick biofilms using Beer's Law. Error bars are provided that account for the spatial correlation of the biofilm's surface. The responsiveness of the biovolumes and plate counts to the increasing contact time of Photo ClO2 were quite different, with a massive 7 log reduction in viable cells (95% confidence interval [CI]: 6.2, 7.9) but a more moderate 73% reduction in biovolume (95% CI: [60%, 100%]). Results are leveraged to quantitatively assess candidate CSLM experimental designs of thick biofilms. CONCLUSIONS: Photo ClO2 kills biofilm bacteria but only partially removes the biofilm from the surface. To maximize statistical confidence in assessing removal, imaging experiments should use fewer pixels in each z-slice, and more importantly, at least two independent experiments even if there is only a single field of view in each experiment. SIGNIFICANCE AND IMPACT OF STUDY: There is limited penetration depth when collecting 3D confocal images of thick biofilms. Removal can be assessed by optimally fitting Beer's Law to all of the intensities in a 3D image and by accounting for the spatial correlation of the biofilm's surface. For thick biofilms, other image analysis approaches are biased or do not provide error bars. We generate unbiased estimates of removal and assess candidate CSLM experimental designs of thick biofilms with different pixilations, numbers of fields of view and number of experiments using the included design tool.

What Factors Are Associated With Failure of Compressive Osseointegration Fixation?

BACKGROUND: Compressive osseointegration is as an alternative to traditional intramedullary fixation. Two- to 10-year survivorship and modes of failure have been reported; however, as a result of relatively small numbers, these studies are limited in their ability to identify risk factors for failure. QUESTIONS/PURPOSES: (1) What is survivorship free from aseptic mechanical and survivorship free from overall failure of compressive osseointegration fixation? (2) What patient factors (age, sex, body mass index [BMI], anatomic location of reconstruction, indication for reconstruction, radiation, chemotherapy) are associated with increased risk of failure? METHODS: Between 2006 and 2014, surgeons at one center treated 116 patients with 137 Compress® implants for lower extremity oncologic reconstructions, revision arthroplasty, and fracture nonunion or malunion. One hundred sixteen implants were available for review with a minimum of 2-year followup (mean, 4 years; range, 2-9 years). Kaplan-Meier survival plots were produced to examine survivorship and Cox regression modeling was used to generate hazard ratios (HRs) for potential risk factors for failure. Patient factors (age, sex, BMI, anatomic location of reconstruction, indication for reconstruction, radiation, chemotherapy) were obtained from chart review and an institutional database. RESULTS: Survivorship free from aseptic mechanical failure was 95% (95% confidence interval [CI], 91%-99%) at 18 months and 93% (95% CI, 86%-99%) at 4 years. Survivorship free from overall failure was 82% (95% CI, 75%-89%) at 18 months and 75% (95% CI, 66%-84%) at 4 years. Risk of overall failure was increased with reconstruction of the proximal tibia (HR, 4.42; 95% CI 0.98-19.9) and distal femur (HR, 1.74; 95% CI, 0.50-6.09) compared to the proximal femur (HR, 1; referent; p = 0.049). Risk of aseptic mechanical failure was increased with reconstruction of the proximal tibia (HR, 1; referent) and distal femur (HR, 0.37; 95% CI, 0.08-1.77) compared with the proximal femur (HR, 0, p = 0.048). Radiation was associated with increased risk of overall failure (HR, 3.85; 95% CI, 1.84-8.02; p < 0.003), but not aseptic mechanical failure. Age, sex, BMI, chemotherapy, and surgical indication were not associated with increased risk of aseptic or overall failure. CONCLUSIONS: This study questions the use of age as a contraindication for the use of this technology and suggests this technology may be considered in proximal femoral reconstruction and for patients with indications other than primary oncologic reconstructions. Future research should establish long-term survivorship data to compare this approach with conventional intramedullary stems and to evaluate the potential benefits of preventing stress shielding and preserving bone stock in revision situations. LEVEL OF EVIDENCE: Level III, therapeutic study.

Handwritten, Soft Circuit Boards and Antennas Using Liquid Metal Nanoparticles.

Soft conductors are created by embedding liquid metal nanoparticles between two elastomeric sheets. Initially, the particles form an electrically insulating composite. Soft circuit boards can be handwritten by a stylus, which sinters the particles into conductive traces by applying localized mechanical pressure to the elastomeric sheets. Antennas with tunable frequencies are formed by sintering nanoparticles in microchannels.

The effect of aging on posterior intertransverse lumbar fusion: a New Zealand white rabbit model.

STUDY DESIGN: In vivo assessment of lumbar spinal fusion between a younger and older cohort of New Zealand white rabbits. OBJECTIVE: Directly compare fusion within young and aged New Zealand white rabbits to establish an aged spinal fusion model translational research. SUMMARY OF BACKGROUND DATA: Prior studies have utilized skeletally mature young rabbits (6-12 mo old) that may not be appropriate as an analog for studying the aging human spine. METHODS: Ten aged (>36 mo old) and 10 young (12 mo old) New Zealand white rabbits underwent a single-level, bilateral, L5-6 posterolateral intertransverse fusion using autogenous iliac crest bone graft. The animals were killed at 6 weeks postoperatively, and the specimens were then evaluated with quantitative microcomputerized tomography and manual palpation by 6 orthopedic surgeons. The fusions were graded as either fused or not fused by each examiner. The spines were then embedded in poly(methyl methacrylate) and cut into 2-mm-thick sections for histologic analysis. RESULTS: A higher percentage of young rabbits were determined to be successfully fused through manual palpation testing compared with the aged rabbits. Micro-computed tomography (CT) analysis revealed a significantly greater fusion mass volume in the younger rabbits than in the older cohort. In addition, the fusion density of the younger rabbits was found to be significantly lower than that of the older rabbits when normalized to the bone density in the nonfused portion of the spine. Histologic analysis showed that the quality of the bone within the fusion mass was consistent between the young and old rabbits. A greater number of young animals had bilateral continuous bone graft compared with the aged animals. CONCLUSIONS: The aged (>36 mo) New Zealand white rabbit model appears to be a valid model to evaluate the effect of aging on lumbar fusion and has the potential to more accurately model conditions that are present in the older human spine.

Patient-specific versus conventional instrumentation for total knee arthroplasty: peri-operative and cost differences.

The role of patient-specific instrumentation in total knee arthroplasty (TKA) is yet to be clearly defined. Current evidence evaluating peri-operative and cost differences against conventional TKA is unclear. We reviewed 356 TKAs between July 2008 and April 2013; 306 TKAs used patient-specific instrumentation while 50 had conventional instrumentation. The patient-specific instrumentation cohort averaged 20.4 min less surgical time (P < 0.01) and had a 42% decrease in operating room turnover time (P = 0.022). At our institution, the money saved through increased operating room efficiency offset the cost of the custom cutting blocks and pre-operative advanced imaging. Routine use of patient-specific TKA can be performed with less surgical time, no increase in peri-operative morbidity, and at no increased cost when compared to conventional TKA.

Auditing the Representation of Female Athletes in Sports Medicine Research: Fifth-Metatarsal Fractures.

Background: Female representation within athletics has increased as a result of Title IX, rising popularity, demand for equal compensation, and greater participation in multiple sports. Despite this, gender disparities in sports medicine research are apparent. This project serves to review the literature available on fifth-metatarsal fractures and assess the representation of female athletes in current literature. Methods: We used a standardized protocol to audit the representation of female athletes in sports science and sports medicine research for fifth-metatarsal fractures. Primary factors included population, athletic caliber, menstrual status, research theme, sample of males and females, journal impact factor, and Altmetric score. Results: Thirty articles met the inclusion criteria. A total of 472 fifth-metatarsal fractures were identified, with 373 of 472 fractures (79%) occurring in males and 99 of 472 (21%) in females. The majority of studies (18/30, 60%) were mixed cohort, followed by 10 male only (33.33%), 1 female only (3.33%), and 1 male vs female (3.33%). Out of 831 total patients in the 18 mixed-cohort studies, 605 of 831 patients (72.8%) were male and 226 of 831 patients (27%) were female. All 18 mixed-sex cohorts investigated health outcomes. Male-only studies evaluated health outcomes and performance metrics. No studies investigated female performance. The one female-only study investigated health outcomes and was the only study to account for menstrual status. There was a single metatarsal fracture in this study population. Conclusion: Females are underrepresented in research regarding sports science and sports medicine research for fifth-metatarsal fractures. Research focused on female-only fifth-metatarsal fracture studies exploring the potential impact of female sex-specific factors such as menstrual status in study design are needed.

Localized ablative immunotherapy enhances antitumor immunity by modulating the transcriptome of tumor-infiltrating Gamma delta T cells.

Gamma delta T cells (γδT cells) play crucial roles in the immune response against tumors, yet their functional dynamics under different cancer therapies remain poorly understood. Laser Ablative Immunotherapy (LAIT) is a novel cancer treatment modality combining local photothermal therapy (PTT) and intratumoral injection of an immunostimulant, N-dihydrogalactochitosan (glycated chitosan, GC). LAIT has been shown to induce systemic antitumor immune responses in pre-clinical studies and clinical trials, eradicating both treated local tumors and untreated distant metastases. In this study, we used LAIT to treat breast tumors in a mouse model and investigated the effects of LAIT on tumor-infiltrating γδT cells using single-cell RNA sequencing (scRNAseq). We characterized the γδT cells from tumors in control, PTT, GC, and LAIT (PTT + GC) groups, by identifying six distinct subtypes: activated, cytotoxic, cycling cytotoxic, IFN-enriched, antigen-presenting, and IL17-producing γδT cells. Differential gene expression analysis revealed that LAIT significantly upregulated genes associated with T cell activation, leukocyte adhesion, and interferon signaling in treated tumor tissues while downregulating genes involved in protein folding and stress responses. LAIT also uniquely increased the proportion of IL17-producing γδT cells, which correlated with prolonged survival in breast cancer patients, as analyzed using TCGA data. Furthermore, the transcriptomic profiles of γδT cells in LAIT-treated tumors closely resembled those in immune checkpoint inhibitor (ICI)-treated patients, suggesting potential synergistic effects. Our findings indicate that LAIT modulates the γδT cell transcriptome, enhancing their antitumor capabilities and providing a basis for combining LAIT with ICI therapy to improve cancer treatment outcomes.

N-dihydrogalactochitosan serves as an effective mucosal adjuvant for intranasal vaccine in combination with recombinant viral proteins against respiratory infection.

Mucosal vaccinations for respiratory pathogens provide effective protection as they stimulate localized cellular and humoral immunities at the site of infection. Currently, the major limitation of intranasal vaccination is using effective adjuvants capable of withstanding the harsh environment imposed by the mucosa. Herein, we describe the efficacy of using a unique biopolymer, N-dihydrogalactochitosan (GC), as a nasal mucosal vaccine adjuvant against respiratory infections. Specifically, we mixed GC with recombinant SARS-CoV-2 trimeric spike (S) and nucleocapsid (NC) proteins to intranasally vaccinate K18-hACE2 transgenic mice, in comparison with Addavax (AV), an MF-59 equivalent. In contrast to AV, intranasal application of GC induces a robust, systemic antigen-specific antibody response and increases the number of T cells in the cervical lymph nodes. Moreover, GC+S+NC-vaccinated animals were largely resistant to the lethal SARS-CoV-2 challenge and experienced drastically reduced morbidity and mortality, with animal weights and behavior returning to normal 22 days post-infection. In contrast, animals intranasally vaccinated with AV+S+NC experienced severe weight loss, mortality, and respiratory distress, with none surviving beyond 6 days post-infection. Our findings demonstrate that GC can serve as a potent mucosal vaccine adjuvant against SARS-CoV-2 and potentially other respiratory viruses. STATEMENT OF SIGNIFICANCE: We demonstrated that a unique biopolymer, N-dihydrogalactochitosan (GC), was an effective nasal mucosal vaccine adjuvant against respiratory infections. Specifically, we mixed GC with recombinant SARS-CoV-2 trimeric spike (S) and nucleocapsid (NC) proteins to intranasally vaccinate K18-hACE2 transgenic mice, in comparison with Addavax (AV). In contrast to AV, GC induces a robust, systemic antigen-specific antibody response and increases the number of T cells in the cervical lymph nodes. About 90 % of the GC+S+NC-vaccinated animals survived the lethal SARS-CoV-2 challenge and remained healthy 22 days post-infection, while the AV+S+NC-vaccinated animals experienced severe weight loss and respiratory distress, and all died within 6 days post-infection. Our findings demonstrate that GC is a potent mucosal vaccine adjuvant against SARS-CoV-2 and potentially other respiratory viruses.

Alternating magnetic fields (AMF) and linezolid reduce Staphylococcus aureus biofilm in a large animal implant model.

OBJECTIVES: We aimed to evaluate the effectiveness of alternating magnetic fields (AMF) combined with antibiotics in reducing Staphylococcus aureus biofilm on metal implants in a large animal model, compared to antibiotics alone. METHODS: Metal plates were inoculated with a clinical MRSA strain and then implanted into thirty-three ewes divided into three groups: positive control, linezolid only, and a combination of linezolid and AMF. Animals had either titanium or cobalt-chrome plates and were sacrificed at 5 or 21 days post-implantation. Blood and tissue samples were collected at various time points post-AMF treatment. RESULTS: In vivo efficacy studies demonstrated significant biofilm reduction on titanium and cobalt-chrome implants with AMF-linezolid combination treatment compared to controls. Significant bacterial reductions were also observed in surrounding tissues and bones. Cytokine analysis showed improved inflammatory responses with combination therapy, and histopathology confirmed reduced inflammation, necrosis, and bacterial presence, especially at 5 days post-implantation. CONCLUSIONS: This study demonstrates that combining AMF with antibiotics significantly reduces biofilm-associated infections on metal implants in a large animal model. Numerical simulations confirmed targeted heating, and in vivo results showed substantial bacterial load reduction and reduced inflammatory response. These findings support the potential of AMF as a non-invasive treatment for prosthetic joint infections.

Case Report: Isosulfan Blue-Related Anaphylaxis.

Anaphylaxis is an acute multisystem syndrome typically resulting from the sudden release of mast cell and basophil-derived mediators into the circulatory system. Isosulfan blue dye is a rare, but known, mediator of anaphylaxis with an incidence between 0.16% and 2% of cases. We report two cases of anaphylaxis attributed to the use of isosulfan blue dye in the intraoperative setting. Both of the patients we report had grade 3 anaphylactic reactions requiring vasopressors to correct significant hypotension. Both patients required overnight monitoring in the intensive care unit with the second patient also requiring continued vasopressor support.

Plan Quality Analysis of Automated Treatment Planning Workflow With Commercial Auto-Segmentation Tools and Clinical Knowledge-Based Planning Models for Prostate Cancer.

This study evaluated the feasibility of using artificial intelligence (AI) segmentation software for volume-modulated arc therapy (VMAT) prostate planning in conjunction with knowledge-based planning to facilitate a fully automated workflow. Two commercially available AI software programs, Radformation AutoContour (Radformation, New York, NY) and Siemens AI-Rad Companion (Siemens Healthineers, Malvern, PA) were used to auto-segment the rectum, bladder, femoral heads, and bowel bag on 30 retrospective clinical cases (10 intact prostate, 10 prostate bed, and 10 prostate and lymph node). Physician-segmented target volumes were transferred to AI structure sets. In-house RapidPlan models were used to generate plans using the original, physician-segmented structure sets as well as Radformation and Siemens AI-generated structure sets. Thus, there were three plans for each of the 30 cases, totaling 90 plans. Following RapidPlan optimization, planning target volume (PTV) coverage was set to 95%. Then, the plans optimized using AI structures were recalculated on the physician structure set with fixed monitor units. In this way, physician contours were used as the gold standard for identifying any clinically relevant differences in dose distributions. One-way analysis of variation (ANOVA) was used for statistical analysis. No statistically significant differences were observed across the three sets of plans for intact prostate, prostate bed, or prostate and lymph nodes. The results indicate that an automated volumetric modulated arc therapy (VMAT) prostate planning workflow can consistently achieve high plan quality. However, our results also show that small but consistent differences in contouring preferences may lead to subtle differences in planning results. Therefore, the clinical implementation of auto-contouring should be carefully validated.

Lung ultrasonography derived B-line scores as predictors of left ventricular end-diastolic pressure and pulmonary artery wedge pressure.

BACKGROUND: Non-invasive assessment of elevated left ventricular end-diastolic pressure (LVEDP) and pulmonary artery wedge pressure (PAWP) in patients with heart diseases is challenging. Lung ultrasonography (LUS) is a promising modality for predicting LVEDP and PAWP. METHODS: Fifty-seven stable ambulatory patients who underwent right and left heart catheterization were included. Following the procedures, LUS was performed in twenty-eight ultrasonographic zones, and the correlation between five different LUS derived B-line scores with LVEDP and PAWP was examined. RESULTS: The B-line index correlated with LVEDP and PAWP, with coefficients of 0.45 (p = 0.006) and 0.30 (p = 0.03), respectively. B-line index showed an AUC of 0.76 for identifying LVEDP > 15 mmHg (p = 0.01) and an AUC of 0.73 for identifying PAWP > 15 mmHg (p = 0.008). Overall, scores performances were similar in predicting LVEDP or PAWP > 15 mmHg. A B-line index ≥ 28 was significantly associated with LVEDP > 15 mmHg (OR: 9.97) and PAWP > 15 mmHg (OR: 6.61), adjusted for age and indication for heart catheterization. CONCLUSIONS: LUS derived B-line scores are moderately correlated with PAWP and LVEDP in patients with heart diseases. A B-line index ≥ 28 can be used to predict elevated LVEDP and PAWP with high specificity.

Single-cell transcriptomics reveals that tumor-infiltrating natural killer cells are activated by localized ablative immunotherapy and share anti-tumor signatures induced by immune checkpoint inhibitors.

Rationale: Natural killer (NK) cells provide protective anti-cancer immunity. However, the cancer therapy induced activation gene signatures and pathways in NK cells remain unclear. Methods: We applied a novel localized ablative immunotherapy (LAIT) by synergizing photothermal therapy (PTT) with intra-tumor delivering of the immunostimulant N-dihydrogalactochitosan (GC), to treat breast cancer using a mammary tumor virus-polyoma middle tumor-antigen (MMTV-PyMT) mouse model. We performed single-cell RNA sequencing (scRNAseq) analysis to unveil the cellular heterogeneity and compare the transcriptional alterations induced by PTT, GC, and LAIT in NK cells within the tumor microenvironment (TME). Results: ScRNAseq showed that NK subtypes, including cycling, activated, interferon-stimulated, and cytotoxic NK cells. Trajectory analysis revealed a route toward activation and cytotoxicity following pseudotime progression. Both GC and LAIT elevated gene expression associated with NK cell activation, cytolytic effectors, activating receptors, IFN pathway components, and cytokines/chemokines in NK subtypes. Single-cell transcriptomics analysis using immune checkpoint inhibitor (ICI)-treated animal and human samples revealed that ICI-induced NK activation and cytotoxicity across several cancer types. Furthermore, ICI-induced NK gene signatures were also induced by LAIT treatment. We also discovered that several types of cancer patients had significantly longer overall survival when they had higher expression of genes in NK cells that were also specifically upregulated by LAIT. Conclusion: Our findings show for the first time that LAIT activates cytotoxicity in NK cells and the upregulated genes positively correlate with beneficial clinical outcomes for cancer patients. More importantly, our results further establish the correlation between the effects of LAIT and ICI on NK cells, hence expanding our understanding of mechanism of LAIT in remodeling TME and shedding light on the potentials of NK cell activation and anti-tumor cytotoxic functions in clinical applications.

Telehealth high-intensity interval exercise and cardiometabolic health in spinal cord injury.

BACKGROUND: The number of exercise trials examining cardiometabolic outcomes in spinal cord injury (SCI) is low, and prescribed exercise is often inconvenient for individuals with SCI to perform within their community. Individuals with SCI experience a myriad of barriers to exercise participation, which can include a lack of time, accessible or usable equipment and facilities, and transportation. Thus, it is imperative to identify effective modes of exercise that provide the greatest overall health benefits but do not require a significant time commitment. Low-volume high intensity interval training (HIIT) has demonstrated the same improvements in cardiometabolic health as moderate intensity exercise training (MIT), despite only requiring 20% of the total time commitment in adults without disabilities and more recently in individuals with SCI. OBJECTIVES: The primary purpose of this study is to integrate a 16 week home-based telehealth HIIT arm crank exercise training program in individuals with SCI and assess changes in cardiometabolic health. METHODS: Men and women between the ages of 19 and 60 with a confirmed diagnosis of SCI between C7 and T12 will be recruited for this study. Participants will be randomized to 16 weeks of telehealth HIIT exercise two days per week or a no-exercise control group. Aerobic capacity, muscular strength, blood lipids, glucose tolerance, resting energy expenditure, blood pressure, and body composition will be assessed at baseline and 16 weeks post-training. DISCUSSION: Inactivity associated with SCI leads to chronic cardiometabolic health conditions. The majority of exercise interventions to date show that exercise is capable of increasing physical function, aerobic capacity, and muscle mass, and strength. Additionally, we have recently shown the ability of HIIT to improve blood lipid and glucose concentrations. Advances in telehealth exercise approaches have improved the capability to prescribe home-based exercise programs. Therefore, we hypothesize that the utilization of a home-based telehealth HIIT program will improve cardiometabolic health markers, yield high adherence (> 75%), and will be more enjoyable in individuals with SCI. TRIAL REGISTRATION: Telehealth High-Intensity Interval Exercise and Cardiometabolic Health in Spinal Cord Injury NCT04940598.

Pulse Arrival Time Is Associated With Hemorrhagic Volume in a Porcine Model: A Pilot Study.

BACKGROUND: Hemorrhage is a major cause of preventable death worldwide, and early identification can be lifesaving. Pulse wave contour analysis has previously been used to infer hemodynamic variables in a variety of settings. We hypothesized that pulse arrival time (PAT), a form of pulse wave contour analysis which is assessed via electrocardiography (ECG) and photoplethysmography (PPG), is associated with hemorrhage volume. METHODS: Yorkshire-Cross swine were randomized to hemorrhage (30 mL/kg over 20 minutes) vs. control. Continuous ECG and PPG waveforms were recorded with a novel monitoring device, and algorithms were developed to calculate PAT and PAT variability throughout the respiratory cycle, termed "PAT index" or "PAT_I." Mixed effects models were used to determine associations between blood loss and PAT and between blood loss and PAT_I to account for clustering within subjects and investigate inter-subject variability in these relationships. RESULTS: PAT and PAT_I data were determined for ∼150 distinct intervals from five subjects. PAT and PAT_I were strongly associated with blood loss. Mixed effects modeling with PAT alone was substantially better than PAT_I alone (R2 0.93 vs. 0.57 and Akaike information criterion (AIC) 421.1 vs. 475.5, respectively). Modeling blood loss with PAT and PAT_I together resulted in slightly improved fit compared to PAT alone (R2 0.96, AIC 419.1). Mixed effects models demonstrated significant inter-subject variability in the relationships between blood loss and PAT. CONCLUSIONS: Findings from this pilot study suggest that PAT and PAT_I may be used to detect blood loss. Because of the simple design of a single-lead ECG and PPG, the technology could be packaged into a very small form factor device for use in austere or resource-constrained environments. Significant inter-subject variability in the relationship between blood loss and PAT highlights the importance of individualized hemodynamic monitoring.

3D morphable systems via deterministic microfolding for vibrational sensing, robotic implants, and reconfigurable telecommunication.

DNA and proteins fold in three dimensions (3D) to enable functions that sustain life. Emulation of such folding schemes for functional materials can unleash enormous potential in advancing a wide range of technologies, especially in robotics, medicine, and telecommunication. Here, we report a microfolding strategy that enables formation of 3D morphable microelectronic systems integrated with various functional materials, including monocrystalline silicon, metallic nanomembranes, and polymers. By predesigning folding hosts and configuring folding pathways, 3D microelectronic systems in freestanding forms can transform across various complex configurations with modulated functionalities. Nearly all transitional states of 3D microelectronic systems achieved via the microfolding assembly can be easily accessed and modulated in situ, offering functional versatility and adaptability. Advanced morphable microelectronic systems including a reconfigurable microantenna for customizable telecommunication, a 3D vibration sensor for hand-tremor monitoring, and a bloomable robot for cardiac mapping demonstrate broad utility of these assembly schemes to realize advanced functionalities.

Metallophobic Coatings to Enable Shape Reconfigurable Liquid Metal Inside 3D Printed Plastics.

Liquid metals adhere to most surfaces despite their high surface tension due to the presence of a native gallium oxide layer. The ability to change the shape of functional fluids within a three-dimensional (3D) printed part with respect to time is a type of four-dimensional printing, yet surface adhesion limits the ability to pump liquid metals in and out of cavities and channels without leaving residue. Rough surfaces prevent adhesion, but most methods to roughen surfaces are difficult or impossible to apply on the interior of parts. Here, we show that silica particles suspended in an appropriate solvent can be injected inside cavities to coat the walls. This technique creates a transparent, nanoscopically rough (10-100 nm scale) coating that prevents adhesion of liquid metals on various 3D printed plastics and commercial polymers. Liquid metals roll and even bounce off treated surfaces (the latter occurs even when dropped from heights as high as 70 cm). Moreover, the coating can be removed locally by laser ablation to create selective wetting regions for metal patterning on the exterior of plastics. To demonstrate the utility of the coating, liquid metals were dynamically actuated inside a 3D printed channel or chamber without pinning the oxide, thereby demonstrating electrical circuits that can be reconfigured repeatably.

Examination of a first-in-class bis-dialkylnorspermidine-terphenyl antibiotic in topical formulation against mono and polymicrobial biofilms.

Biofilm-impaired tissue is a significant factor in chronic wounds such as diabetic foot ulcers. Most, if not all, anti-biotics in clinical use have been optimized against planktonic phenotypes. In this study, an in vitro assessment was performed to determine the potential efficacy of a first-in-class series of antibiofilm antibiotics and compare outcomes to current clinical standards of care. The agent, CZ-01179, was formulated into a hydrogel and tested against mature biofilms of a clinical isolate of methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa ATCC 27853 using two separate methods. In the first method, biofilms were grown on cellulose discs on an agar surface. Topical agents were spread on gauze and placed over the biofilms for 24 h. Biofilms were quantified and imaged with confocal and scanning electron microscopy. In the second method, biofilms were grown on bioabsorbable collagen coupons in a modified CDC biofilm reactor. Coupons were immersed in treatment for 24 h. The first method was limited in its ability to assess efficacy. Efficacy profiles against biofilms grown on collagen were more definitive, with CZ-01179 gel eradicating well-established biofilms to a greater degree compared to clinical standards. In conclusion, CZ-01179 may be a promising topical agent that targets the biofilm phenotype. Pre-clinical work is currently being performed to determine the translatable potential of CZ-01179 gel.

Mechanochromic Stretchable Electronics.

Soft and stretchable electronics are promising for a variety of applications such as wearable electronics, human-machine interfaces, and soft robotics. These devices, which are often encased in elastomeric materials, maintain or adjust their functionality during deformation, but can fail catastrophically if extended too far. Here, we report new functional composites in which stretchable electronic properties are coupled to molecular mechanochromic function, enabling at-a-glance visual cues that inform user control. These properties are realized by covalently incorporating a spiropyran mechanophore within poly(dimethylsiloxane) to indicate with a visible color change that a strain threshold has been reached. The resulting colorimetric elastomers can be molded and patterned so that, for example, the word "STOP" appears when a critical strain is reached, indicating to the user that further strain risks device failure. We also show that the strain at color onset can be controlled by layering silicones with different moduli into a composite. As a demonstration, we show how color onset can be tailored to indicate a when a specified frequency of a stretchable liquid metal antenna has been reached. The multiscale combination of mechanochromism and soft electronics offers a new avenue to empower user control of strain-dependent properties for future stretchable devices.