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Cerebral aneurysms (CA), an abnormal bulge in the arteries that supply blood to the brain, are prone to rupture and can cause hemorrhagic stroke. Physicians can treat CA by blocking blood flow to the aneurysmal sac via clipping of the aneurysm neck via open procedure, or endovascular occlusion of the aneurysm with embolic materials to promote thrombus formation to prevent further inflow of blood into the aneurysm. Endovascular treatment options for CA still have significant limitations in terms of safety, usability in coagulopathic patients, and risks of device migration. Bioactive embolic therapies, consisting of non-toxic bioresorbable materials that encourage the growth of neointima across the aneurysm neck, are needed to improve the healing of CA. In this work, the bioinspired silk-elastinlike protein-based polymer (SELP 815K), was used to embolize aneurysms in a rabbit elastase model. SELP 815K effectively embolized the model aneurysms in vivo, achievinggt;90% occlusion, using commercial microcatheters. No device-associated adverse effects were observed in any of the animals, and SELP 815K showed no cytotoxicity. SELP embolization did not show any deleterious effects to local tissues, and features consistent with reendothelialization of the aneurysm neck were noted in histological examination one-month post-embolization. SELP 815K shows promise as an embolic treatment for unruptured CA. STATEMENT OF SIGNIFICANCE: Unruptured cerebral aneurysms are present in approximately 3% of the population, with a fatality rate of up to 65% upon rupture. In this work a silk-elastinlike protein polymer (SELP) is explored as a liquid embolic for occlusion of cerebral aneurysms. This embolic exists as a liquid at room temperature before rapidly forming a gel at physiological temperature. This shape filling property was used to successfully occlude cerebral aneurysms in rabbits, with stable occlusion persisting for over thirty days. SELP occlusions show evidence for reendothelialization of the aneurysm sac and provide an opportunity for delivery of bioactive agents to further improve treatments.

Radiation-induced proctitis (RIP) is a debilitating adverse event that occurs commonly during lower abdominal radiotherapy. The lack of prophylactic treatment strategies leads to diminished patient quality of life, disruption of radiotherapy schedules, and limitation of radiotherapy efficacy due to dose-limiting toxicities. Semisynthetic glycosaminoglycan ethers (SAGE) demonstrate protective effects from RIP. However, low residence time in the rectal tissue limits their utility. We investigated controlled delivery of GM-0111, a SAGE analogue with demonstrated efficacy against RIP, using a series of temperature-responsive polymers to compare how distinct phase change behaviors, mechanical properties and release kinetics influence rectal bioaccumulation. Poly(lactic acid)-co-(glycolic acid)-block-poly(ethylene glycol)-block-poly(lactic acid)-co-(glycolic acid) copolymers underwent macroscopic phase separation, expelling >50% of drug during gelation. Poloxamer compositions released GM-0111 cargo within 1 h, while silk-elastinlike copolymers (SELPs) enabled controlled release over a period of 12 h. Bioaccumulation was evaluated using fluorescence imaging and confocal microscopy. SELP-415K, a SELP analogue with 4 silk units, 15 elastin units, and one elastin unit with lysine residues in the monomer repeats, resulted in the highest rectal bioaccumulation. SELP-415K GM-0111 compositions were then used to provide localized protection from radiation induced tissue damage in a murine model of RIP. Rectal delivery of SAGE using SELP-415K significantly reduced behavioral pain responses, and reduced animal mass loss compared to irradiated controls or treatment with traditional delivery approaches. Histological scoring showed RIP injury was ameliorated for animals treated with GM-0111 delivered by SELP-415K. The enhanced bioaccumulation provided by thermoresponsive SELPs via a liquid to semisolid transition improved rectal delivery of GM-0111 to mice and radioprotection in a RIP model.

Radiation-induced proctitis (RIP) is the most common clinical adverse effect for patients receiving radiotherapy as part of the standard course of treatment for ovarian, prostate, colon, and bladder cancers. RIP limits radiation dosage, interrupts treatment, and lowers patients' quality of life. A prophylactic treatment that protects the gastrointestinal tract from deleterious effects of radiotherapy will significantly improve patient quality of life and may allow for higher and more regular doses of radiation therapy. Semi-synthetic glycosaminoglycan (GAG), generated from the sulfation of hyaluronic acid, are anti-inflammatory but have difficulty achieving therapeutic levels in many tissues. To enhance the delivery of GAG, we created an in situ gelling rectal delivery system using silk-elastinlike protein polymers (SELPs). Using solutions of SELP 815K (which contains 6 repeats of blocks comprised of 8 silk-like units, 15 elastin-like units, and 1 lysine-substituted elastin-like unit) with GAG GM-0111, we created an injectable delivery platform that transitioned in

While commonly known for degradation of the extracellular matrix, matrix metalloproteinases (MMPs) exhibit broad potential for use in targeting of bioactive and imaging agents in cancer treatment. MMPs are upregulated at all stages of expression in cancers. A comprehensive analysis of published literature on expression of all MMP subtypes at the genetic, protein, and activity levels in normal and diseased tissues indicate targeting applicability in a variety of cancers. This expression significantly increases at advanced cancer stages, providing an improved opportunity for controlled release in higher-stage patients. Since MMPs are integral at every stage of metastasis, MMP roles in cancer are discussed with a focus on MMP distribution and mobility within cells and tumors for cancer targeting applications. Several strategies for MMP utilization in targeting - such as matrix degradation, MMP cleavage, MMP binding, and MMP-induced environmental changes - are addressed.

Chronic toxicity evaluations of nanotechnology-based drugs are essential to support initiation of clinical trials. Ideally such evaluations should address the dosing strategy in human applications and provide sufficient information for long-term usage. Herein, we investigated one-year toxicity of non-surface modified silica nanoparticles (SNPs) with variations in size and porosity (Stober SNPs 46 ± 4.9 and 432.0 ± 18.7 nm and mesoporous SNPs 466.0 ± 86.0 nm) upon single dose intravenous administration to female and male BALB/c mice (10 animal/sex/group) along with their human blood compatibility. Our evidence of clinical observation and blood parameters showed no significant changes in body weight, cell blood count, nor plasma biomarker indices. No significant changes were noted in post necropsy examination of internal organs and organ-to-body weight ratio. However, microscopic examination revealed significant amount of liver inflammation and aggregates of histocytes with neutrophils within the spleen suggesting an ongoing or resolving injury. The fast accumulation of these plain SNPs in the liver and spleen upon IV administration and the duration needed for their clearance caused these injuries. There were also subtle changes which were attributed to prior infarctions or resolved intravascular thrombosis and included calcifications in pulmonary vessels, focal cardiac fibrosis with calcifications, and focal renal injury. Most of the pathologic lesions were observed when large, non-porous SNPs were administered. Statistically significant chronic toxicity was not observed for the small non-porous particles and for the mesoporous particles. This one-year post-exposure evaluation indicate that female and male BALB/c mice need up to one year to recover from acute tissue toxic effects of silica nanoparticles upon single dose intravenous administration at their 10-day maximum tolerated dose. Further, ex vivo testing with human blood and plasma revealed no hemolysis or complement activation following incubation with these silica nanoparticles. These results can inform the potential utility of silica nanoparticles in biomedical applications such as controlled drug delivery where intravenous injection of the particles is intended.

Silk-elastinlike protein polymers (SELPs) self-assemble into nanostructures when designed with appropriate silk-to-elastin ratios. Here, we investigate the effect of insertion of a matrix metalloproteinase-responsive peptide sequence, GPQGIFGQ, into various locations within the SELP backbone on supramolecular self-assembly. Insertion of the hydrophilic, enzyme-degradable sequence into the elastin repeats allows the formation of dilution-stable nanostructures, while insertion into the hydrophobic silk motifs inhibited self-assembly. The SELP assemblies retained their lower critical solution temperature (LCST) thermal response, allowing up to eightfold volumetric changes due to temperature-induced size change. A model hydrophobic drug was incorporated into SELP nanoassemblies utilising a combination of precipitation, incubation and tangential flow filtration. While the nanoconstructs degraded in response to MMP activity, drug release kinetics was independent of MMP concentration. Drug release modelling suggests that release is driven by rates of water penetration into the SELP nanostructures and drug dissolution. In vitro testing revealed that SELP nanoassemblies reduced the immunotoxic and haemolytic side effects of doxorubicin in human blood while maintaining its cytotoxic activity.

[][1] ILLUSTRATION: LEONARD DUPOND We asked young scientists to write an advertisement that answers this question: How will food options, food availability, and individuals' food choices change in the future? A selection of their suggested marketing campaigns is below. Follow NextGen Voices on Twitter with hashtag #NextGenSci. Read previous NextGen Voices survey results at . —Jennifer Sills Tired of managing your diet? Health Capsule provides non-invasive, cognitive control of your hunger, satiation, and weight. Made possible by deep brain stimulation and neuromodulation technology, this environmentally sustainable capsule will keep you healthy and fit while satisfying all your cravings. Put calculating your calories and carbon footprint behind you! Saima Naz Lahore, 54570, Pakistan. Email: saimanaz85{at}gmail.com Try our new Bacteri-Os: The Sustainable Microbial Sustenance™! We start with the freshest plasmids and gene fragments, harvested from diverse biospheres and raised organically and sustainably. Then, we splice and dice these into stable, non-infective carrier organisms, ensuring production of all secondary metabolites and metabolic fuels growing eukaryotes might need: yeasty vitamins, siderophore mineral sponges, and essential amino acids. A little sprinkle of HMG-CoA adds your fats and sterols, et voila! Buy your Bacteri-Os pellets wherever fine nutritional cakes and shakes are sold. Michael A. Tarselli SLAS, Oak Brook, IL 60523, USA. Email: tarselli{at}gmail.com Tired of your 3D-printed food all tasting the same? Make your fab food fabulous! Our FlavorPack™ inks will make your proteins meatier, desserts sweeter, and veggies crunchier. Compatible with any home fab unit! Mark Martin Jensen Massachusetts General Hospital, Department of Surgery, Harvard Medical School, Boston, MA 02114, USA. Email: MMJensen{at}MGH.Harvard.edu Send us your DNA, and we will predict your food preferences! Receive your personalized food basket, with a day-by-day diet program. We will send you full meals and personalized smoothies based on your genetic taste predisposition. We know what you love; it's in your DNA. Ada Gabriela Blidner Laboratorio de Inmunopatologia, IBYME-CONICET, 1428 Ciudad Autonoma de Buenos Aires, Argentina. Twitter: @adagbb Introducing Broth-3D technologies, by machine-learning chefs! Broth recipes use boiled local and seasonal ingredients. Miss your grandmother's recipes and the beautiful plating of the past? We've uploaded images of meals created by 33,003 grandmothers and distilled their knowledge into 3D-printable dishes using broth solidifiers. Add nostalgic structure to your dish! Athanasia Nikolaou Department of Physics, Sapienza University of Rome, Rome, Italy. Email: athanasia.nikolaou{at}protonmail.com Convert polluted ambient air into basic nutrients with Smart Straw! Sensors in this nano-technological device identify potentially nutritious particles suspended in the air around you. Just take a sip, press the Convert button, and imbibe basic nutrients through chemical reactions and filtering. Emre Ozan Polat ICFO–The Institute of Photonic Sciences, Castelldefels, Barcelona, 08860, Spain. Email: emre-ozan.polat{at}icfo.eu With intravenous (IV) nutrients, you no longer need to make time for trivial things like sitting down to a full meal! Plus, our targeted modulation of the hunger hormone ghrelin means no more hunger pangs. Don't be tied down by mundane human concerns like eating and weight gain—make time for more with IV nutrients! Mallory Peterson Penn State College of Medicine, Hershey, PA 17033, USA. Email: mpeterson1{at}pennstatehealth.psu.edu Beeph™ is the newest, tastiest insect patty! If you're old enough to remember Kobe, you're in for a treat! Made with pure, farm-raised Periplaneta and synthetic spice blend for that wholesome goodness your family loves. When you're hungry for burgers, think Beeph™—It's what's for dinner! Donnelly A. West Walnut Creek, CA 94597, USA. Twitter: @catscausetypos Sustainable Steaks provides the most scrumptious, environmentally sensitive beef. Our steaks are sourced from natural grasslands and prairies, where livestock now fills the ecological roles left vacant by the wild grazers that used to roam these plains. Using our open-source FoodFootprint supplementary feeding system, we enhance natural grazing with protein-rich fodder to optimize animal growth while minimizing methane production and water consumption. At only $219.00/kg (including carbon taxes and ecological levies), our steaks are affordable for the whole family. Falko Buschke Centre for Environmental Management, University of the Free State, Bloemfontein, 9300, South Africa. Email: falko.buschke{at}gmail.com As Earth's temperatures rose, temperate zones were lost. Do you miss sweet temperate fruits? Welcome to our Moon Farm. Our fruit trees are planted in hybri-soil and artificial air that simulate Earth's environment from 5000 years ago. Pick fruits with your family or ship to your doorstep with MoonEx. Freshness guaranteed. Yongsheng Ji Department of Human Parasitology, Anhui Medical University, Hefei, Anhui, 230032, China. Email: jiyongshengkey{at}hotmail.com West Siberian Citrus Company offers a bountiful array of lemons, oranges, grapefruits, and limes. Once a permafrosted no-man's land, Siberia is now a gorgeous Garden of Eden. With no deep freeze days during the growing season, we guarantee that our fruits have attained maximum size and flavor upon harvest. For a limited time only, get your dose of Vitamin “Sea” with our genetically engineered Florida-style oranges; they accurately replicate that 2023 pre-flood tang! Voted “Better Flavor” than both Alaskan and Nunavut Oranges. Kyle J. Isaacson Biomedical Engineering, University of Utah, Salt Lake City, UT 84112, USA. Twitter: @kjisaacson Want to feel like a globalist glutton from the greedy years of centuries past? Cicada Steaks let you relive the joy and horror of eating fried animal flesh! The new recipe of textured Insekt™ protein, marbled with saturated fats, evokes steaks Grandma will remember from her childhood when people ate cows. Matilda Newton University of Colorado, Boulder, CO 20309, USA. Email: matilda.newton{at}colorado.edu Do you long for the days before the Great Climate Shift when meat wasn't only for special occasions? Are you fed up with paying outrageous beef and pork prices? Well don't have a cow! Why pig out when you can GRUB! out. GRUB! (Great Rations Using Bugs!) is a delicious, nutritious insect protein that is packed full of vitamins and minerals. Whether it's GRUB! burgers on the grill or GRUB! taco Tuesdays, make GRUB! part of your family's dinner plans. Eric Britt Moore Department of Agronomy, Iowa State University, Ames, IA 50011, USA. Email: ebm256{at}iastate.edu Using the precision breeding technology CRISPR, scientists have developed a high-yield, disease-resistant cassava. Cassava, a historically crucial staple for millions of people, is now an even more reliable food source, providing food security to the developing world where it is needed most. Syed Shan-e-Ali Zaidi Gembloux Agro-Bio Tech, University of Liege, Gembloux Namur, 5030, Belgium. Email: shan.e.ali{at}outlook.com Our dedicated team of food engineers has pioneered a technique to convert the chemical bonds in wood, turning indigestible cellulose into a scrumptious starch. The result? A rustic delicacy ushering in the new era of staple wood-based foods. Try our signature, honey-coated wood chips at a Trader Joe's near you! Divyansh Agarwal Statistics, The Wharton School, University of Pennsylvania, Philadelphia, PA 19104, USA. Twitter: @divyansh_aga Introducing high-energy, nutrient-rich Wherice, a unique mix of wheat and rice! Just 100 g of this tasty, digestible food fulfills your energy requirements for the day, saving you time and money. Sustainable Wherice can be cultivated in high-temperature areas of the world three times a year. Sudhakar Srivastava Institute of Environment and Sustainable Development, Banaras Hindu University, Varanasi, Uttar Pradesh, 221005, India. Email: sudhakar.srivastava{at}gmail.com [1]: /embed/graphic-1.gif

Rationale: Intraoperative bleeding impairs physicians' ability to visualize the surgical field, leading to increased risk of surgical complications and reduced outcomes. Bleeding is particularly challenging during endoscopic-assisted surgical resection of hypervascular tumors in the head and neck. A tool that controls bleeding while marking tumor margins has the potential to improve gross tumor resection, reduce surgical morbidity, decrease blood loss, shorten procedure time, prevent damage to surrounding tissues, and limit postoperative pain. Herein, we develop and characterize a new system that combines pre-surgical embolization with improved visualization for endoscopic fluorescence image-guided tumor resection. Methods: Silk-elastinlike protein (SELP) polymers were employed as liquid embolic vehicles for delivery of a clinically used near-infrared dye, indocyanine green (ICG). The biophysical properties of SELP, including gelation kinetics, modulus of elasticity, and viscosity, in response to ICG incorporation using rheology, were characterized. ICG release from embolic SELP was modeled in tissue phantoms and via fluorescence imaging. The embolic capability of the SELP-ICG system was then tested in a microfluidic model of tumor vasculature. Lastly, the cytotoxicity of the SELP-ICG system in L-929 fibroblasts and human umbilical vein endothelial cells (HUVEC) was assessed. Results: ICG incorporation into SELP accelerated gelation and increased its modulus of elasticity. The SELP embolic system released 83 ± 8% of the total ICG within 24 hours, matching clinical practice for pre-surgical embolization procedures. Adding ICG to SELP did not reduce injectability, but did improve the gelation kinetics. After simulated embolization, ICG released from SELP in tissue phantoms diffused a sufficient distance to deliver dye throughout a tumor. ICG-loaded SELP was injectable through a clinical 2.3 Fr microcatheter and demonstrated deep penetration into 50-µm microfluidic-simulated blood vessels with durable occlusion. Incorporation of ICG into SELP improved biocompatibility with HUVECs, but had no effect on L-929 cell viability. Principle Conclusions: We report the development and characterization of a new, dual-functional embolization-visualization system for improving fluorescence-imaged endoscopic surgical resection of hypervascular tumors.

Interstitial cystitis (IC), also known as painful bladder syndrome, is a debilitating chronic condition with many patients failing to respond to current treatment options. Rapid clearance, mucosal coating, and tight epithelium create strong natural barriers that reduce the effectiveness of many pharmacological interventions in the bladder. Intravesical drug delivery (IDD) is the administration of therapeutic compounds or devices to the urinary bladder via a urethral catheter. Previous work in improving IDD for IC has focused on the sustained delivery of analgesics within the bladder and other small molecule drugs which do not address underlying inflammation and bladder damage. Therapeutic glycosaminoglycans (GAG) function by restoring the mucosal barrier within the bladder, promoting healing responses, and preventing irritating solutes from reaching the bladder wall. There is an unmet medical need for a therapy that provides both acute relief of symptoms while alleviating underlying physiological sources of inflammation and promoting healing within the urothelium. Semi-synthetic glycosaminoglycan ethers (SAGE) are an emerging class of therapeutic GAG with intrinsic anti-inflammatory and analgesic properties. To reduce SAGE clearance and enhance its accumulation in the bladder, we developed a silk-elastinlike protein polymer (SELP) based system to enhance SAGE IDD. We evaluated in vitro release kinetics, rheological properties, impact on bladder function, pain response, and bladder inflammation and compared their effectiveness to other temperature-responsive polymers including Poloxamer 407 and poly(lactic-co-glycolic acid)-poly(ethylene glycol). SAGE delivered via SELP-enhanced intravesical delivery substantially improved SAGE accumulation in the urothelium, provided a sustained analgesic effect 24 h after administration, and reduced inflammation.

We asked young scientists this question: How do broad interests benefit your science? Scientists with a variety of hobbies responded that their extracurricular activities have enhanced a wide range of skills, from creativity to communication to resilience. Many also mentioned the value of clearing their minds and relaxing. Follow NextGen and share your own hobbies on Twitter with #NextGenSci. As a rock climber, you have to risk falling in order to become better ; the same principle applies in science. Realizing this has made me look at research failures in a more positive light—less as a demonstration of incompetence, and more of an opportunity to learn something and build resilience. I've learned that reminding yourself of your own competence (on the wall or in the lab) is a useful way to build up the courage to take more risks.

We asked young scientists: Are our schools and universities adequately prepared to educate young people for future challenges? What is the most pressing issue in your field, and what one improvement could your country make to its current education system to prepare students to face it? The responses expressed concerns about the current state of education in countries around the world. Many students lack access to the information they need, and those with access are often constrained by curriculum that emphasizes rote learning and isolated subjects. Our respondents suggested a variety of improvements to prepare the next generation for success.

Many PhD students have no intention of remaining in academia, and outdated university curricula do them a disservice by not offering training for careers in industry, argues Kyle Isaacson, a PhD student in biomedical engineering.

Photography usually requires optics in conjunction with a recording device (an image sensor). Eliminating the optics could lead to new form factors for cameras. Here, we report a simple demonstration of imaging using a bare CMOS sensor that utilizes computation. The technique relies on the space variant point-spread functions resulting from the interaction of a point source in the field of view with the image sensor. These space-variant point-spread functions are combined with a reconstruction algorithm in order to image simple objects displayed on a discrete LED array as well as on an LCD screen. We extended the approach to video imaging at the native frame rate of the sensor. Finally, we performed experiments to analyze the parametric impact of the object distance. Improving the sensor designs and reconstruction algorithms can lead to useful cameras without optics.

We demonstrate a computational image reconstruction using only a bare CMOS sensor and accidental imperfections. Once sensor is calibrated using LED array, complex objects displayed not only on LED array but also on LCD display could be reconstructed. We are now pursuing the direct use of raw sensor images in machine learning without reconstruction.

Recombinant silk-elastinlike protein polymers (SELPs) combine the biocompatibility and thermoresponsiveness of human tropoelastin with the strength of silk. Direct control over structure of these monodisperse polymers allows for precise correlation of structure with function. This work describes the fabrication of the first SELP nanogels and evaluation of their physicochemical properties and thermoresponsiveness. Self-assembly of dilute concentrations of SELPs results in nanogels with enhanced stability over micelles due to physically crosslinked beta-sheet silk segments. The nanogels respond to thermal stimuli via size changes and aggregation. Modifying the ratio and sequence of silk to elastin in the polymer backbone results in alterations in critical gel formation concentration, stability, aggregation, size contraction temperature, and thermal reversibility. The nanogels sequester hydrophobic compounds and show promise in delivery of bioactive agents.