Biology subjects

Traverso, G.

Publications and source records attributed to Traverso, G..

15 recordsLinked to original sources

bioRxiv2026

Kinetics of Hypoglycemia in Diabetes Patients Informs Development of New Modes of Glucagon Therapy

Insulin therapy revolutionized the care of patients with diabetes starting [~]100 years ago, yet insulin-induced hypoglycemia remains a serious life-threatening complication of insulin therapy. Glucagon is a highly effective treatment; however current dosage forms remain under-utilized due to poor patient compliance. The development of improved and situation-specific glucagon therapies remains challenging due to the poor drug stability and incomplete knowledge of the kinetics of different hypoglycemic events. Thus, we analyzed continuous glucose monitor (CGM) data from 1135 patients with type 1 diabetes (T1D) representing 246.18 patient years. We show that a surprisingly large proportion of hypoglycemic episodes (20-30%) are follow-on events resulting from under-treatment of prior events, and that the average duration of independent hypoglycemic events can last up to 79 to 108 minutes. We further show that the kinetics of hypoglycemic onset and persistence varies significantly by patient history, severity, time of occurrence. Guided by these findings, we recognize the opportunity to develop high-density, readily-soluble, and thermostable (ReST) solid glucagon formulations, and painless application-specific microneedle-patches that are in line with the timing needs of T1D patients who are awake and asleep. Thus, we demonstrate (1) on-demand patches for rapid prevention or treatment of mild hypoglycemia during the day, and (2) enzyme-driven hypoglycemia-responsive patches supporting autonomous glucagon release during the night. We show excellent in vitro glucagon stability, loading, and release kinetics of both systems and demonstrate their ability to treat hypoglycemia in diabetic animals. The engineering of these delivery systems demonstrates the potential of human CGM data and solid glucagon formulations to enable new modes of glucagon therapy, thereby expanding the clinical role of glucagon beyond the emergency setting.

bioengineering↗

bioRxiv2025

Enhancing HIPEC for Ovarian Cancer using Adjunctive Biomaterials

Ovarian cancer is one of the most lethal gynecological malignancies, with high mortality rates primarily due to late-stage diagnoses and extensive peritoneal metastases. Despite improvements in surgical and chemotherapeutic treatments, the prognosis for advanced ovarian cancer remains poor, highlighting the urgent need for innovative therapeutic approaches. Hyperthermic intraperitoneal chemotherapy (HIPEC) has emerged as a promising treatment, delivering heated chemotherapeutic agents directly into the peritoneal cavity post-cytoreductive surgery. However, HIPEC adoption is limited by three critical complications: suboptimal therapeutic efficacy in resistant tumors; abdominal adhesion formation; and systemic toxicity, including cisplatin-induced nephrotoxicity. This study investigates carbon monoxide gas- entrapping materials (CO-GEMs) as a novel multifunctional adjunctive therapy to address the three HIPEC limitations simultaneously. CO-GEMs effectively encapsulate and deliver carbon monoxide, leveraging the differential effects of CO in cancerous where it has been shown to reduce tumor burden. In ovarian cancer models, CO-GEMs significantly enhanced cisplatin efficacy, reducing the metastatic tumor burden by 46.6% through the downregulation of drug resistance pathways, including the IL-17, TNF, and NF-{kappa}B pathways; ECM receptor interaction, and VEGF signaling. CO-GEMs also prevented peritoneal adhesion formation by suppressing inflammatory cell infiltration and collagen deposition, with a significant reduction in adhesion severity scores. Additionally, enteral CO-GEMs provided significant nephroprotection against cisplatin-induced acute kidney injury, as demonstrated by reduced blood urea nitrogen levels. CO-GEMs represent a promising innovation that simultaneously improves HIPEC therapeutic efficacy, prevents surgical complications, and reduces systemic toxicity. This multifunctional approach addresses multiple clinical limitations of HIPEC, potentially transforming treatment outcomes for patients with advanced ovarian cancer through an enhanced therapeutic index and improved safety profile.

bioengineering↗

bioRxiv2025

Monolithic Shape-Shifting Absorbable Implants for Long-Term Contraception

Reversible contraceptives empower women to prevent unintended pregnancies and enable family planning. However, the need for frequent dosing with pills or injections often leads to suboptimal medication adherence and reduced effectiveness-an issue common to many chronic conditions. Long-acting drug delivery implants offer a compelling alternative by enabling autonomous, multi-year drug release, thereby improving real-world adherence and treatment outcomes. However, user acceptability and access are limited by need for invasive insertion and surgical end-of-life removal, particularly in low-resource settings, as well as by limited drug loading and suboptimal drug utilization efficiency, which constrain both the duration of therapy and the range of drugs that can be effectively delivered. To address these limitations, we developed the Monolithic Shape-shifting Absorbable Implants for Chronic Care (MoSAIC) platform-a minimally invasive, fully bioresorbable system that integrates compacted drug formulations with a space-efficient device architecture. This approach reduces implant size, eliminates the need for surgical removal, and prolongs therapeutic duration compared to existing implants. We develop compacted formulations of the contraceptive drug levonorgestrel (LNG), and other poorly water-solubility drugs, demonstrating exceptional drug loading (100% w/w) and multi-year sustained drug release via surface-mediated dissolution in rats. When incorporated into MoSAIC devices, these formulations enable high-efficiency drug loading and zero-order drug release kinetics with geometrically tunable rates and durations. As a result, MoSAIC systems can be designed to be smaller, less invasive, and/or longer lasting than current contraceptive implants such as Jadelle(R) and Nexplanon(R). The MoSAIC platform expands access to reversible contraception and supports long-term medication adherence, with the potential to improve health outcomes and quality of life. More broadly, it provides a flexible approach for delivering other potent, low-solubility therapeutics and lays the foundation for a "dose it and forget it" paradigm in chronic disease management, where adherence is designed into the therapy itself.

bioengineering↗

bioRxiv2025

Identification and Validation of Small Molecules with Mucin-Selective Regiospecific Binding in the Gastrointestinal Tract

Oral drug delivery is a widely used method of drug administration; however, achieving localized drug release at specific regions of the gastrointestinal (GI) tract is generally accomplished by using broad environmental differences. The GI tract is a complex system with regional differences in composition, such as selective expression of mucin glycoproteins in different organs. Here, we identify small molecule ligands that can selectively bind to the different mucins to localize drug delivery to the small intestine and stomach. We demonstrate up to a 10-fold increase in particle binding to these organs and up to a 4-fold increase in selectivity compared to chitosan. Additionally, we observe up to a 9-fold increase in budesonide concentration in the small intestine and a 25-fold increase in tetracycline concentration in the stomach. These results show that we have developed a versatile platform capable of sequestering a variety of drugs in certain GI tract organs.

bioengineering↗

bioRxiv2024

An ingestible, battery-free, tissue-adhering robotic interface for non-invasive and chronic electrostimulation of the gut

Ingestible electronics have the capacity to transform our ability to effectively diagnose and potentially treat a broad set of conditions. Current applications could be significantly enhanced by addressing poor electrode-tissue contact, lack of navigation, short dwell time, and limited battery life. Here we report the development of an ingestible, battery-free, and tissue-adhering robotic interface (IngRI) for non-invasive and chronic electrostimulation of the gut, which addresses challenges associated with contact, navigation, retention, and powering (C-N-R-P) faced by existing ingestibles. We show that near-field inductive coupling operating near 13.56 MHz was sufficient to power and modulate the IngRI to deliver therapeutically relevant electrostimulation, which can be further enhanced by a bio-inspired, hydrogel-enabled adhesive interface. In swine models, we demonstrated the electrical interaction of IngRI with the gastric mucosa by recording conductive signaling from the subcutaneous space. We further observed changes in plasma ghrelin levels, the "hunger hormone," while IngRI was activated in vivo, demonstrating its clinical potential in regulating appetite and treating other endocrine conditions. The results of this study suggest that concepts inspired by soft and wireless skin-interfacing electronic devices can be applied to ingestible electronics with potential clinical applications for evaluating and treating gastrointestinal conditions.

bioengineering↗

bioRxiv2023

Thermo-Responsive Polymers Targeting Inflammation in Murine Colitis

Targeting the site of inflammation is an ideal approach for treating inflammatory bowel disease (IBD). Inflammation targeting enables maximal drug-on-target effects while minimizing off-target side effects. Negatively charged drug carriers have been shown to facilitate drug delivery to inflamed colon mucosa after local administration. To modulate the negative charges and integrate responsiveness to stimuli, here we describe thermo-responsive, inflammation-targeting (TRIT) hydrogels based on functionalized poly(N-isopropylacrylamide-co-methacrylic acid) (PNIPAM-MAA). We show that both chemical modification types and polymer molecular weights affect the resultant microgels adhesion to the inflamed colon in dextran sulfate sodium (DSS)-induced murine colitis in vivo. Further, we quantified the correlations between microgels adhesion and colitis severity for individual mice, demonstrating that the microgels adhesion correlated directly with weight loss percentage in DSS-treated mice. By exploiting charge-mediated interaction and thermo-responsiveness, TRIT hydrogels represent a promising strategy to target inflamed colon mucosa as a drug delivery platform for colonic IBD treatment. TeaserThis study developed thermo-responsive, inflammation-targeting (TRIT) hydrogels that harness charge-mediated interaction and sol-to-gel transition to target inflamed colon mucosa as a new approach for treating inflammatory bowel disease.

bioengineering↗

bioRxiv2023

Electroadhesive hydrogel interface for prolonged mucosal theranostics

Establishing a robust and intimate mucosal interface that allows medical devices to remain within lumen-confined organs for extended periods has valuable applications, particularly for gastrointestinal (GI) theranostics. Here, we report the development of e-GLUE, an electroadhesive hydrogel interface for robust and prolonged mucosal retention following electrical activation. Notably, this novel mucosal adhesion mechanism can increase the adhesion energy of hydrogels on the mucosa by up to 30-fold and enable in vivo GI retention of e-GLUE devices for up to 30 days. Strong mucosal adhesion occurs within one minute of electrical activation, despite the presence of luminal fluid, mucus exposure, and organ motility, thereby ensuring compatibility with complex in vivo environments. In swine studies, we demonstrate the utility of e-GLUE for mucosal hemostasis, sustained local delivery of therapeutics, and intimate biosensing in the GI tract. This system can enable improved treatments for various health conditions, including gastrointestinal bleeding, inflammatory bowel disease, and diagnostic applications in the GI tract and beyond.

bioengineering↗

bioRxiv2023

A Vibrating Ingestible BioElectronic Stimulator Modulates Gastric Stretch Receptors for Illusory Satiety

Effective therapies for obesity either require invasive surgical or endoscopic interventions or high patient adherence, making it challenging for the nearly 42% of American adults who suffer from obesity to effectively manage their disease. Gastric mechanoreceptors sense distension of the stomach and perform volume-dependent vagal signaling to initiate the gastric phase and influence satiety. In this study, we developed a new luminal stimulation modality to specifically activate these gastric stretch receptors to elicit a vagal afferent response commensurate with mechanical distension. Here we developed the Vibrating Ingestible BioElectronic Stimulator (VIBES) pill - an ingestible device that performs luminal vibratory stimulation to activate mechanoreceptors and stroke mucosal receptors, which induces serotonin release as well as yields a hormonal metabolic response commensurate with a fed state. We evaluated VIBES across 108 meals in swine which consistently led to diminished food intake ([~]40%, p< 0.0001) and minimized the weight gain rate (p< 0.03) as compared to untreated controls. Application of mechanoreceptor biology could transform our capacity to help patients suffering from nutritional disorders.

pathology↗

bioRxiv2022

Drinkable, liquid in situ-forming and tough hydrogels for gastrointestinal therapeutics

Tablets and capsules are a cornerstone of medicine, but these solid dosage forms can be challenging to swallow for geriatric and pediatric patients. While liquid formulations are easier to ingest, these formulations lack the capacity to localize therapeutics and excipients nor act as controlled release devices. To bridge the advantages of solid and liquid dosage forms, here we describe drug formulations based on liquid in situ-forming and tough (LIFT) hydrogels. Drug-loaded LIFT hydrogels are formed directly in the stomach through the sequential ingestion of a crosslinker solution of calcium and dithiol crosslinkers, followed by the ingestion of a drug-containing polymer solution of alginate and 4-arm poly(ethylene glycol)-maleimide. We show that LIFT hydrogels are mechanically tough and able to robustly form in the presence of complex gastric fluid and in vivo in rat and porcine stomachs. LIFT hydrogels are retained within the porcine stomach for up to 24 h, biocompatible, and safely cleared. These hydrogels deliver a total dose comparable to unencapsulated drug but with delayed and lower maximum drug plasma concentrations, providing a method for controlled release that may mitigate drug toxicity. Co-encapsulation of lactase as a model biologic drug and calcium carbonate mitigated gastric-mediated deactivation of encapsulated enzyme in rat and porcine models. We also demonstrate the potential of these hydrogels to encapsulate and protect a model therapeutic bacterium, E. coli Nissle 1917, against acid. LIFT hydrogels present a biocompatible means of tough, double-network hydrogel formation in situ in the gastric cavity, and may expand medication access for patients with difficulty swallowing.

bioengineering↗

bioRxiv2022

Synthetic extremophiles: Species-specific formulations for microbial therapeutics and beyond.

Microorganisms have been used for millennia to produce food and medicine and are now being developed as products themselves to treat disease and boost crop production. However, as required for these new applications, maintaining high viability throughout manufacturing, transportation and use remains a significant challenge requiring sophisticated cold-chains and packaging. In fact, we found that commercial microbial products (probiotics) provide a poor solution to this challenge, in particular for key industrial organisms like E. coli. To overcome this technological gap, we report the development of synthetic extremophiles of industrially important gram-negative bacteria (E. coli Nissle 1917, Ensifer meliloti), gram positive bacteria (Lactobacillus plantarum) and yeast (Saccharomyces boulardii). Specifically, we developed a high throughput pipeline to define species-specific materials that allow these organisms to survive drying, elevated temperatures, organic solvents and even ionizing radiation. We enhanced the stability of E.coli Nissle 1917 by >4 orders of magnitude over commercial formulations and demonstrate the capacity to remain viable while undergoing tableting and pharmaceutical methodologies involving organic solvents. The development of synthetic materials-based enhanced stabilization stands to transform our capacity to apply micro-organisms in extreme environments including those found on Earth as well as in space. One-Sentence SummaryFragile therapeutic bacteria can be made to survive the manufacturing extremes normally reserved for small molecule drugs.

microbiology↗

bioRxiv2022

A machine learning liver-on-a-chip system for safer drug formulation

Drug metabolism leads to biotransformations of pharmaceutical substances that alter drug efficacy, toxicity, as well as drug interactions. Modeling these processes ex vivo stands to greatly accelerate our capacity to develop safe and efficacious drugs and formulations. Recognizing the liver as the primary site of drug metabolism, here we report a novel whole-tissue ex vivo liver screening platform that enabled modeling of hepatic metabolism and tracking of hepatotoxic drug metabolites. We applied the system for the characterization of acetaminophen (APAP) metabolism and identified interactions that can mitigate the generation of toxic metabolites ex vivo. Combining our experimental platform with state-of-the-art machine learning, we validated two novel functional excipients that can prevent APAP hepatotoxicity in vivo in mice. To assess translational potential, we prototyped a novel solid dosage form with controlled release of both APAP and our functional excipients. Our this platform provides innovative potential access to actionable data on drug metabolism to support the development of new therapeutic approaches.

bioengineering↗

bioRxiv2022

Absorbable Conductive Electrotherapeutic Scaffolds (ACES) for Enhanced Peripheral Nerve Regeneration and Stimulation

While peripheral nerve stimulation (PNS) has shown promise in applications ranging from peripheral nerve regeneration after injury to therapeutic organ stimulation, clinical implementation has been impeded by various technological limitations, including surgical placement, lead migration, and atraumatic removal. Here, we describe the design and validation of a new platform for nerve regeneration and interfacing: Absorbable, Conductive, Electrotherapeutic Scaffolds (ACES). ACES are comprised of an alginate/poly-acrylamide interpenetrating network hydrogel optimized for both open and minimally invasive percutaneous approaches. In a rodent model of sciatic nerve repair, ACES significantly improved motor and sensory recovery (p < 0.05), increased muscle mass (p < 0.05), and increased axonogenesis (p < 0.05). Triggered dissolution of ACES enabled atraumatic, percutaneous removal of leads at forces significantly lower than controls (p < 0.05). In a porcine model, ultrasound-guided percutaneous placement of leads with an injectable ACES near the femoral and cervical vagus nerves facilitated stimulus conduction at significantly greater lengths than saline controls (p < 0.05). Overall, ACES facilitated lead placement, stabilization, stimulation and atraumatic removal enabling therapeutic PNS as demonstrated in small and large animal models.

bioengineering↗

bioRxiv2022

Ingestible capsule for detecting labile inflammatory biomarkers in situ

Transient molecules in the gastrointestinal (GI) tract, such as nitric oxide and hydrogen sulfide, are key signals and mediators of inflammatory bowel disease (IBD). Because these molecules are extremely short-lived in the body, they are difficult to detect. To track these reactive molecules in the GI tract, we have developed a miniaturized device that integrates genetically-engineered probiotic biosensors with a custom-designed photodetector and readout chip. Leveraging the molecular specificity of living sensors, we genetically encoded bacteria to respond to IBD-associated molecules by luminescing. Low-power electronic readout circuits (nanowatt power) integrated into the device convert the light from just 1 L of bacterial culture into a wireless signal. We demonstrate biosensor monitoring in the GI tract of small and large animal models and integration of all components into a sub-1.4 cm3 ingestible form factor capable of supporting wireless communication. The wireless detection of short-lived, disease-associated molecules could support earlier diagnosis of disease than is currently possible, more accurate tracking of disease progression, and more timely communication between patient and their care team supporting remote personalized care.

synthetic biology↗

bioRxiv2020

Individualized System for Augmenting Ventilator Efficacy (iSAVE):A Rapidly deployable system to expand ventilator capacity

The COVID-19 pandemic is overwhelming healthcare systems worldwide. A significant portion of COVID-19 patients develop pneumonia and acute respiratory distress syndrome (ARDS), necessitating ventilator support. Some health systems do not have the capacity to accommodate this surge in ventilator demand, leading to shortages and inevitable mortality. Some clinicians have, of necessity, jerry-rigged ventilators to support multiple patients, but these devices lack protected air streams or individualized controls for each patient. Moreover, some have not been tested under conditions of ARDS. We have developed the Individualized System for Augmenting Ventilator Efficacy (iSAVE), a rapidly deployable platform to more safely use a single ventilator to simultaneously support multiple critically-ill patients. The iSAVE enables patient-specific volume and pressure control and incorporates safety features to mitigate cross-contamination between patients and flow changes due to patient interdependencies within the respiratory circuit. Here we demonstrate through simulated and in vivo pig evaluation the capacity of the iSAVE to support a range of respiratory clinical states. By leveraging off-the-shelf components that are readily available to intensive care unit (ICU) caregivers, the iSAVE could potentially be translated for human application to expand the ventilation capacity of hospitals using existing ventilators, minimizing the need to procure additional ventilators.

physiology↗

bioRxiv2019

Computationally guided high-throughput design of self-assembling drug nanoparticles

Nanoformulations are transforming our capacity to effectively deliver and treat a myriad of conditions. However, many nanoformulation approaches still suffer from high production complexity and low drug loading. One potential solution relies on harnessing co-assembly of drugs and small molecular excipients to facilitate nanoparticle formation through solvent exchange without the need for chemical synthesis, generating nanoparticles with up to 95% drug loading. However, there is currently no understanding which of the millions of possible combinations of small molecules can result in the formation of these nanoparticles. Here we report the development of a high-throughput screening platform coupled to machine learning to enable the rapid evaluation of such nanoformulations. Our platform identified 101 novel self-assembling drug nanoparticles from 2.1 million pairings derived from 788 candidate drugs with one of 2686 excipients, spanning treatments for multiple diseases and often harnessing well-known food additives, vitamins, or approved drugs as carrier materials - with potential for accelerated approval and translation. Given their long-term stability and potential for clinical impact, we further characterize novel sorafenib-glycyrrhizin and terbinafine-taurocholic acid nanoparticles ex vivo and in vivo. We anticipate that this platform could accelerate the development of safer and more efficacious nanoformulations with high drug loadings for a wide range of therapeutics.

bioengineering↗