An implantable system for opioid safety.

Naloxone can effectively rescue victims from opioid overdose, but less than 5% survive due to delayed or absent first responder intervention. Current overdose reversal systems face key limitations, including low user adherence, false positive detection, and slow antidote delivery. Here, we describe a subcutaneously implanted robotic first responder to overcome these challenges.

Potentiating the effect of immunotherapy in pancreatic cancer using gas-entrapping materials.

Immune checkpoint inhibitors (ICIs) show limited success in treating pancreatic ductal adenocarcinoma (PDAC), largely due to immune evasion mechanisms, including downregulating expression of major histocompatibility complex class I (MHC-I). Our retrospective analysis demonstrated that smoking - a state of elevated CO exposure - is correlated with increased MHC I expression in pancreatic tumors. Here we tested our hypothesis that introducing exogenous CO augments the anti-cancer effects of immunotherapy.

Designing for medication adherence in inflammatory bowel disease: multi-disciplinary approaches for self-administrable biotherapeutics.

Biotherapeutics are among the therapeutics that have revolutionized standard inflammatory bowel disease (IBD) treatment, which was previously limited to mesalamine, 5-aminosalicylic acid, corticosteroids, and classical immunosuppressants. Self-administrable biotherapeutics for IBD would enable home-based treatment and reduce the burden on medical infrastructure. Self-administration is made possible through subcutaneous injectable, oral, and rectal dosage forms.

Composite Hyaluronic Acid Gas-Entrapping Materials to Promote Wound Healing.

Tissue repair is often impaired in pathological states, highlighting the need for innovative wound-healing technologies. This study introduces composite hyaluronic acid gas-entrapping materials (GEMs) delivering carbon monoxide (CO) to promote wound healing in pigs. These composite materials facilitate burst release followed by sustained release of CO over 48 h.

Assessing the reliability of automated cell count analysis of synovial fluid in the setting of revision total knee arthroplasty.

Purpose: The diagnostic challenges of periprosthetic joint infection (PJI) for orthopedic surgeons are significant. Prior research has indicated that patients with adverse reactions, dislocations, and aseptic loosening exhibit a heightened count of white blood cells (WBC) in their synovial fluid, along with an increased polymorphonuclear cell percentage (PMN%). The prevalence of false-positive results raises concerns about the reliability of these tools in distinguishing aseptic failure from PJI.

Cephalopod-inspired jetting devices for gastrointestinal drug delivery.

Needle-based injections currently enable the administration of a wide range of biomacromolecule therapies across the body, including the gastrointestinal tract, through recent developments in ingestible robotic devices. However, needles generally require training, sharps management and disposal, and pose challenges for autonomous ingestible systems. Here, inspired by the jetting systems of cephalopods, we have developed and evaluated microjet delivery systems that can deliver jets in axial and radial directions into tissue, making them suitable for tubular and globular segments of the gastrointestinal tract.

Local drug delivery challenges and innovations in spinal neurosurgery.

The development of novel therapeutics in the field of spinal neurosurgery faces a litany of translational challenges. Achieving precise drug targeting within the confined spaces associated with the spinal cord, canal and vertebra requires the development of next generation delivery systems and devices. These must be capable of overcoming inherent barriers related to drug diffusion, whilst concurrently ensuring optimal drug distribution and retention.

Synthetic extremophiles via species-specific formulations improve microbial therapeutics.

Microorganisms typically used to produce food and pharmaceuticals are now being explored as medicines and agricultural supplements. However, maintaining high viability from manufacturing until use remains an important challenge, requiring sophisticated cold chains and packaging. Here we report synthetic extremophiles of industrially relevant gram-negative bacteria (Escherichia coli Nissle 1917, Ensifer meliloti), gram-positive bacteria (Lactobacillus plantarum) and yeast (Saccharomyces boulardii).

Modulation of diabetic wound healing using carbon monoxide gas-entrapping materials.

Diabetic wound healing is uniquely challenging to manage due to chronic inflammation and heightened microbial growth from elevated interstitial glucose. Carbon monoxide (CO), widely acknowledged as a toxic gas, is also known to provide unique therapeutic immune modulating effects. To facilitate delivery of CO, we have designed hyaluronic acid-based CO-gas-entrapping materials (CO-GEMs) for topical and prolonged gas delivery to the wound bed.

Prospective study on the impact of BEAM versus FEAM conditioning on occurrence of neutropenic enterocolitis and on transplant outcome in lymphoma patients.

Introduction: Carmustine (BCNU), etoposide, cytarabine, and melphalan (BEAM) are a widely used high-dose chemotherapy regimen for autologous stem cell transplantation transplant (ASCT) in lymphoid malignancies. During BCNU shortages, some centers switched to fotemustine-substituted BEAM (FEAM). Neutropenic enterocolitis (NEC) is a life-threatening complication occurring after intestinal mucosa damage related to intensive chemotherapy.

Thiol Coordination Softens Liquid Metal Particles To Improve On-Demand Conductivity.

Achieving tunable rupturing of eutectic gallium indium (EGaIn) particles holds great significance in flexible electronic applications, particularly pressure sensors. We tune the mechanosensitivity of EGaIn particles by preparing them in toluene with thiol surfactants and demonstrate an improvement over typical preparations in ethanol. We observe, across multiple length scales, that thiol surfactants and the nonpolar solvent synergistically reduce the applied stress requirements for electromechanical actuation.

Evaluation of Circulating Endothelial Cells as Direct Marker of Endothelial Damage in Allo-Transplant Recipients at High Risk of Hepatic Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome.

Sinusoidal obstruction syndrome (SOS), also known as veno-occlusive disease (VOD), is a rare but potentially fatal complication following allogenic hematopoietic cell transplantation (allo-HCT). Timely identification of SOS/VOD to allow for prompt treatment is critical, but identifying a VOD-predictive biomarker remains challenging. Given the pivotal role of endothelial dysfunction in SOS/VOD pathophysiology, the CECinVOD study prospectively evaluated levels of circulating endothelial cells (CECs) in patients undergoing allo-HCT with a myeloablative conditioning (MAC) regimen to investigate the potential of CEC level in predicting and diagnosing SOS/VOD.

Screening oral drugs for their interactions with the intestinal transportome via porcine tissue explants and machine learning.

In vitro systems that accurately model in vivo conditions in the gastrointestinal tract may aid the development of oral drugs with greater bioavailability. Here we show that the interaction profiles between drugs and intestinal drug transporters can be obtained by modulating transporter expression in intact porcine tissue explants via the ultrasound-mediated delivery of small interfering RNAs and that the interaction profiles can be classified via a random forest model trained on the drug-transporter relationships. For 24 drugs with well-characterized drug-transporter interactions, the model achieved 100% concordance.

A vibrating ingestible bioelectronic stimulator modulates gastric stretch receptors for illusory satiety.

Effective therapies for obesity require invasive surgical and endoscopic interventions or high patient adherence, making it challenging for patients with 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.

Secure and Stable Wireless Communication for an Ingestible Device.

Wireless communication enables an ingestible device to send sensor information and support external on-demand operation while in the gastrointestinal (GI) tract. However, it is challenging to maintain stable wireless communication with an ingestible device that travels inside the dynamic GI environment as this environment easily detunes the antenna and decreases the antenna gain. In this paper, we propose an air-gap based antenna solution to stabilize the antenna gain inside this dynamic environment.

Impact of different chemotherapy regimens on intestinal mucosal injury assessed with bedside ultrasound: a study in 213 AML patients.

Introduction: Neutropenic enterocolitis (NEC) is a life-threatening complication reported in patients with acute myeloid leukemia (AML) following chemotherapy (CHT). Intensive induction and consolidation CHT may damage intestinal mucosa leading to a NEC episode (NECe). NEC reported mortality may be up to 30-60%.

Percutaneous Intratumoral Immunoadjuvant Gel Increases the Abscopal Effect of Cryoablation for Checkpoint Inhibitor Resistant Cancer.

Percutaneous cryoablation is a common clinical therapy for metastatic and primary cancer. There are rare clinical reports of cryoablation inducing regression of distant metastases, known as the "abscopal" effect. Intratumoral immunoadjuvants may be able to augment the abscopal rate of cryoablation, but existing intratumoral therapies suffer from the need for frequent injections and inability to confirm target delivery, leading to poor clinical trial outcomes.