Khalil Basel Ramadi

Injectable bioelectronics offer a minimally invasive approach to peripheral nerve stimulation but remain limited by onboard energy storage and fragile leads. Here, we present SEED, a leadless, battery-free bioelectronic interface engineered for percutaneous delivery through a standard 14-gauge needle. SEED (Stimulating Electrode for Electroceutical Delivery) operates in the magnetoquasistatic regime using low-frequency (65 kilohertz) resonant inductive coupling, externalizing waveform generation and control, enabling programmable neuromodulation without onboard active electronics. A spiral-helix electrode geometry promotes longitudinal nerve engagement while limiting off-target field spread. Benchtop and ex vivo characterization demonstrates precise, programmable control of stimulation frequency, pulse width, and amplitude under physiologically relevant conditions. In vivo validation in a rat sciatic nerve model confirms frequency-locked motor responses and graded neural recruitment following percutaneous deployment. SEED exhibits strong radiopacity and acoustic contrast, supporting compatibility with ultrasound and computed tomography for image-guided neuromodulation. This platform provides a scalable pathway toward minimally invasive bioelectronic therapies.

Oral ingestion of drugs remains the most convenient method for pharmacotherapy. However, oral absorption is hampered by digestive enzymes and the intestinal epithelial barrier. Here we investigate the ability of electrical stimuli to biologically modulate intestinal permeability. We demonstrate that pulsed electrical stimulation increases intestinal permeability, facilitating transport of chemical species across the epithelium. We evaluate the effects of several stimulation parameters in silico and subsequently characterize the biological effects in vitro using Caco-2 colorectal cancer cells, and an acute in vivo intestinal model. Our findings suggest that these effects may be mediated through calcium-dependent interactions with tight junction proteins which induce a reversible permeability increase differing based on the total charge delivered, amplitude and frequency of the current delivered. Pulsed electrical stimulation could be a potential strategy for transiently modulating the intestinal barrier.

Anxiety disorders are highly prevalent and often refractory to existing treatments, motivating the development of alternative neuromodulatory strategies. Peripheral bioelectronic approaches targeting the gut–brain axis such as vagus nerve stimulation (VNS) demonstrate that modulation of visceral afferent pathways can influence central emotional circuits. Gastric electrical stimulation (GES) is a clinically established therapy for gastrointestinal motility disorders. While the stomach is densely innervated by vagal afferents, the effect of GES on anxiety-related behavior has not been systematically examined. We sought to identify neural pathways engaged by GES and effects of continuous chronic GES on behavior. To do this, we developed a gastric stimulation platform for rodents, a fully implantable, untethered system enabling chronic neuromodulation in freely moving rats. We combined this with cross-species whole-brain activity mapping in mice to interrogate circuit-level mechanisms. Using open field and elevated plus mazes, together with machine-learning-based behavioral tracking and multivariate modeling, we show that acute GES induces a robust, context-dependent anxiogenic phenotype characterized by reduced exploration and increased freezing, particularly in novel open-field environments. In contrast, chronic GES produces a divergent post-stimulation behavioral profile marked by enhanced exploratory behavior relative to acutely stimulated animals, indicating temporally dynamic reorganization of anxiety-related behavior. Principal component analysis and hierarchical clustering further revealed that stimulation reshapes the multivariate structure of behavioral features rather than shifting animals along a single anxiety continuum. Whole-brain c-Fos mapping revealed anatomically distributed modulation of limbic–cortical networks following gastric stimulation, including suppression of ventral medial entorhinal cortex, excitation of nucleus tractus solitarii and heterogeneous recruitment of amygdalar and hippocampal subregions. These circuit-level patterns align with the behavioral dissociation between contextual exploration and explicit threat avoidance, providing convergent cross-species evidence that gastric stimulation engages distributed anxiety-related networks. Together, these findings establish the first freely moving behavioral model of chronic gastric neuromodulation, demonstrate temporally dynamic and context-sensitive effects on anxiety-like behavior, and provide systems-level validation that the stomach can serve as a viable peripheral access point for modulating central emotional circuits.

Tracking gastrointestinal (GI) transit in preclinical models is essential for assessing gut motility and drug delivery. Current preclinical methods rely on end-to-end transit measurements or emptying studies that require terminal endpoints and organ explanation. Clinically, radiopaque Sitz markers are administered orally and their position in the GI tract is assessed through radiography. Sitz markers have been in use since 1969 and are typically mass-produced using industrial molding or extrusion, resulting in a single, fixed geometry with limited tunability. We present a stereolithography (SLA)-based method to fabricate customizable radiopaque markers using additive manufacturing with a barium sulfate (BaSO4)-doped resin. We demonstrate precise control over marker geometry, a key advantage over existing markers. Furthermore, we apply this method in vivo, tracking markers in a live rat model from ingestion to excretion using serial CT imaging. We systematically investigate how changes in marker geometry impact GI residency and transit time. Our results show that 3D printed markers provide a flexible and tunable platform for radiopaque marker fabrication and enable investigation of the fundamental relationship between physical properties of a marker and its performance in a dynamic biological environment. This work establishes a novel, tunable platform for GI motility evaluation and drug delivery studies.

Postoperative gastric leak after bariatric surgery is a serious complication associated with prolonged treatment, repeated interventions, and substantial morbidity. Endoscopic internal drainage using double pigtail stents is widely adopted. However, current stents, originally designed for biliary use and often based on simple cylindrical geometries, are not optimized for post-bariatric gastric leak anatomy, mechanical support, or fluid drainage. Here, we present BRIDGE (Biodegradable aRchitected Internal DrainaGE), a stent concept integrating triply periodic minimal surface (TPMS) architectures to control mechanical compliance, kink resistance, and drainage performance. Using computational modeling, mechanical testing, and benchtop flow studies, we evaluate TPMS designs and identify volume fraction as a key parameter balancing flexibility, structural integrity, and hydraulic performance. TPMS-integrated designs tolerated a 7.1-fold smaller bend radius than a commercial stent without kinking and achieved up to a 2-fold increase in drainage. We also developed a stereolithography-printable biodegradable resin and fabricated a prototype lattice-integrated stent.

Postoperative gastric leaks (GL), a serious complication of bariatric surgery, are often managed by endoscopic internal drainage using biliary double‐pigtail stents (DPS). However, conventional extruded thermoplastic (e.g., polyethylene, polyurethane, and polytetrafluoroethylene) stents often provide inadequate drainage, suboptimal anatomical conformity, and are prone to migration, collectively hindering patient recovery and contributing to an adverse event rate of 13.8%. To address these limitations, we developed PETALS (Personalized Endoscopic Transmural Abscess Leak Solution), an analytical framework for the optimization of stent designs dedicated to transmural fluid drainage. We identified stent length and diameter as critical geometric parameters influencing fluid dynamics. Using PETALS, we designed a family of stents with longitudinal fins fabricated by stereolithography (SLA) using Formlabs Flexible 80A resin. The Lily design, a six‐segment PETALS construct, achieved a 32% reduction in hydraulic resistance and a 30% increase in flow rate compared with a commercial DPS in a benchtop GL model, while also exhibiting superior flexibility. PETALS thus enables the fabrication of patient‐specific, additively manufactured stents with increased flow rate, potentially reducing complications and shortening hospitalization.

Objective. Neurological disorders often arise from specific regions of dysfunction in the brain. One approach to target these pathologic regions is through chemical delivery using intracerebral implants. Previous works have designed implants that are small and flexible, minimizing the mechanical mismatch between inorganic implants and soft organic brain tissue. Most of these implants are simple cylindrical catheters with inflow and outflow ports at either end of the cylinder. This limits the region and volume of tissue that can be dosed. We sought to develop novel catheter designs that permit targeting of larger volumes of brain tissue while maintaining minimal footprint to minimize gliosis. Approach. We present the design, fabrication, and testing of a novel helical-shaped microfluidic catheter we term SPIRAL (Strategic Precision Infusion for Regional Administration of Liquid). SPIRAL leverages rational fluidic design of multiple fluid outflow ports to vary infused fluid spatial distribution across brain regions. We used in silico, in vitro, and in vivo models to test the fluid dynamic functionality and chronic viability of SPIRAL. Results. Our computational fluid dynamics (CFDs) models illustrate how SPIRAL can be configured to permit simultaneous dosing through multiple outflow ports yielding a variable fluid distribution compared to a straight catheter. We show how CFD in silico models can be used to optimize dimensions of channel openings across SPIRAL, to achieve uniform flow through channels and validate these results in vitro. We show how chronically implanted SPIRAL catheters do not increase gliosis compared to standard straight catheters of similar dimensions or materials. Significance. Our helical intracerebral drug delivery catheter facilitates fluid localization while maintaining minimal invasiveness. SPIRAL could enable multiregional brain access and improve therapeutic efforts in the treatment of neurological diseases.