Giovanni Traverso

Diagnosing and treating small intestinal disorders such as bleeding, inflammatory bowel disease, and tumors present challenges because of limited access to this anatomical compartment. We present BIOSENTER, a bioinspired soft enteroscopic robot for deep procedures in the small intestine that addresses locomotion, steering, and intervention constraints of existing soft robotic systems. BIOSENTER features a hollow cylinder architecture comprising a linearly deformable soft pneumatic actuator as the body, two radially expandable soft pneumatic actuators wrapped with kirigami sleeves as the head and tail, a central hollow channel for accessory endoscopic tools, and a control box for navigation. Inspired by snake locomotion, the robotic body incorporates a fiber-reinforced actuator with four embedded inflatable chambers, enabling steering and axial expansion. The dynamic kirigami sleeves generate an anchoring force of ∼1.5 newtons on intestinal mucosa while requiring substantially less radial expansion than the corresponding nonkirigami configuration. A reinforced central channel supports tool passage for diagnostic and therapeutic interventions. The control box enables locomotion and steering at autonomous speeds of ∼100 millimeters per minute in vitro and ∼43 millimeters per minute in tissue-covered tubing. BIOSENTER successfully navigated the collapsed, tortuous small intestine for 2 meters in 11 minutes, with gentle forward pushing forces of 2.2 to 6.4 newtons in pig studies. In vivo pig studies demonstrated technical feasibility of tissue biopsy, localized fluid delivery as a model for future drug administration, and real-time visualization of the deep intestine, without macroscopic overdistention or visible tissue damage under the tested conditions.

Hydrogel-based materials have been widely studied for their cartilage-like mechanical properties, but their clinical translation remains limited by the lack of a robust strategy to integrate tough hydrogels with bone-anchoring components while preserving structural integrity in anatomically relevant implant geometries. Here, we report a titanium–hydrogel platform addressing this challenge through a versatile interfacial design strategy. Tunable poly(vinyl alcohol)/polyacrylamide (PVA/PAAm) hydrogels were integrated with titanium components by combining silane surface modification with a triply periodic minimal surface (TPMS) architecture, yielding an interfacial bonding energy exceeding 1300 J m⁻². As examples, a hydrogel-based hip joint maintained low-friction articulation and structural integrity over 500,000 loading cycles (3000 N peak load, 12° rotation), while an artificial intervertebral disc reproduced asymmetric compression–tension behavior, symmetric torsional response, and dissipated over 80% of impact energy. Incorporation of antibiotics further enabled controlled drug release. This platform establishes a general strategy for integrating load-bearing hydrogels with rigid fixation components, enabling functional orthopedic implants with cartilage-like bearing surfaces.

Ingestible and implantable electronic devices are transforming personalized healthcare by enabling real-time sensing, targeted therapy and diagnostic capabilities. However, powering these systems remains a major challenge owing to biocompatibility concerns and the environmental impact of conventional batteries. Here we present a bioresorbable magnesium–molybdenum trioxide (Mg–MoO ₃ ) paper battery that delivers high electrochemical performance under physiological conditions and safely degrades over time. The battery provides a peak open-circuit voltage of 1.84 V and supports capsule-scale ingestible electronic systems incorporating bioresorbable power sources for two key gastrointestinal applications: battery-assisted radio-frequency identification tags for wireless medication tracking and capsule systems for electroceutical therapy. In vivo studies in swine models have demonstrated robust operation within the gastrointestinal tract and compatibility with clinically relevant use cases. This study establishes a foundation for safe, high-performance and bioresorbable power sources in biomedical electronics, enabling retrieval-free, eco-friendly devices that eliminate electronic waste in the gastrointestinal environment.

A stable symbiosis within the microbiome‐host axis is essential for human health. However, preventing microbiome dysbiosis using biomaterials remains challenging due to their unpredictable influence on microbiome evolution. Inspired by the defensive niche of symbiotic mucosa, we have developed a biointerface that forms an engineered mucosa‐inspired dynamic niche to prevent pathogenic dysbiosis. This biointerface features a dynamic zwitterionic network that emulates the mucosa's biophysical defensive functions. Notably, by leveraging its dynamic niche, the biointerface restricts microbial attachment and aggregation, thereby preventing biofilm formation. Comprehensive metagenomic analyses reveal that microbial communities adapt to this biofilm‐preventive dynamic biointerface compositionally and functionally. In particular, Gram‐negative bacteria were relatively reduced, along with decreased abundance of pathways associated with virulence and biofilm formation. Consequently, the mucosa‐inspired biointerface intrinsically prevents the development of pathogenic dysbiosis. This study demonstrates the groundbreaking potential of material‐based niche engineering to guide the ecological shifts of microbial communities from the material scale.

Poor adherence to oral drug regimens adversely affects treatment outcomes and contributes substantially to preventable healthcare costs, underscoring the need for long-acting drug delivery systems that sustain therapeutic levels over extended periods. To address this, we developed an origami-inspired, oral drug delivery dosage form capable of prolonged residence in the gastric cavity. This system achieves ease of administration and extended gastric residency through geometric design and shape optimization, allowing the dosage form to fold inside a standard ingestible capsule. Upon the capsule’s dissolution in the stomach, the dosage form rapidly transforms into its deployed configuration. Our formulation and manufacturing techniques enable the development of a long-acting dosage form with up to 40% weight loading capacity of sample drugs, such as moxifloxacin. The high surface-area-to-volume ratio of the origami design enables approximately linear release kinetics over the observed time window of candidate drugs. We incorporated pH-sensitive elements that dissolve in the neutral portions of the GI tract into the dosage form to promote its dissociation and safe transit in the intestine. In vitro and in vivo studies using swine models demonstrated extended gastric residency of up to three weeks (with a minimum of one week) and an approximately constant release rate for three days. Endoscopic and radiographic evaluations of the animal models confirmed that the dosage forms safely pass through the intestine without causing gastrointestinal obstruction or injury.

Ingestible electronic systems offer a minimally invasive means to continuously monitor core body temperature, providing critical insights into a range of health conditions. However, the size of ingestible sensors often limits their use, particularly in paediatric populations. Here we report a miniaturized ingestible temperature sensor for continuous internal monitoring. The device integrates a 1 mm × 1 mm low-power (10 nW) integrated circuit, a 5 mm × 5 mm antenna for wireless backscatter communication and a coin-cell battery. The fully encapsulated system measures just 6 mm in diameter and 4 mm in height, dimensions aligned with those of US Food and Drug Administration-approved osmotic controlled-release oral delivery system and smaller than video capsule endoscopy devices, thus minimizing the risk of gastrointestinal retention. We evaluate the sensor in swine models under diverse physiological and pathophysiological conditions. This includes use in ambulatory multi-day monitoring, scenarios with inflammation-induced altered gastrointestinal transit and deployment alongside intravascular devices for vascular navigation and guidance.

Drug delivery to the oesophagus poses unique challenges, including rapid transit time due to gravity and the presence of a stratified squamous non-keratinized epithelium. Here, to rapidly identify formulations of excipients for enhanced drug delivery to the oesophagus, we developed an oesophageal tissue screening system consisting of specialized custom plates, to incorporate gravity effects, and excised oesophageal mucosa tissues. Using the screening system, we built an excipient library identifying the most effective non-toxic permeation enhancers and selected the formulation that could prolong the retention on the oesophageal mucosa. We identified an absorption enhancer that resulted in a 876-fold increase in the oesophageal transport of a model drug (4 kDa) in pig tissue. We validated this formulation in human oesophageal tissue and in vivo in pigs with the model drug and infliximab (149 kDa), demonstrating enhanced permeability. We characterized the mechanism of the approach, noting its capacity for enhanced delivery without causing cellular disruption of the oesophageal tissue. The oesophageal tissue screening system shows promise for high-throughput screening of effective oesophageal drug delivery systems.

Ribonucleic acid (RNA)-based therapeutics have emerged as promising methods of disease treatment due to their ability to target the human genome and influence protein production, their versatility, and their relative lack of toxicity compared to other gene therapies. However, the RNA therapeutic design space is extremely large, encompassing multiple variables, including codon identities, secondary structure, and design of specific regions. RNA therapeutic optimization is difficult due to the impracticality of exploring such a vast design space experimentally. To address this limitation, deep learning methods have been employed to optimize RNA therapeutic development. In this review, we examine the application of deep learning models across three key aspects of RNA therapeutic development (RNA structure prediction, CRISPR activity, and RNA delivery), highlighting major contributions in these fields and analyzing how deep learning model architectures could affect model performance. We then discuss challenges associated with using deep learning for RNA therapeutics, such as computational and data limitations. Finally, we offer perspectives on areas for future exploration, such as emerging model architectures and methods of integration with more advanced high-throughput screening techniques. Ultimately, this review provides an overview of how deep learning is used in RNA therapeutic development and how it can evolve in the future.

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.