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Medication non-adherence represents a healthcare challenge, generating over $100 billion in additional costs annually in the USA. Here, the authors developed a resorbable and ingestible system designed for assessing medication adherence.

Figure 1. Schematic illustration of capsule based, biodegradable medication adherence tracking system with envisioned scenario for clinical use. A, Bio-RFID capsule administration. B, Shielding coating dissolution and payload release C, Monitoring of the Tag ID and frequency range, recording of the payload for tracking adherence. D, Dissolution and biosorption of the coating, tag and the capsule.

Ingestible electronic devices could transform gastrointestinal medicine by combining diagnostic and therapeutic functions into a single miniature device. But challenges related to device miniaturization, power-efficient integrated circuit design and data security remain to be addressed.

Wanted: biomaterials for a risky journey. Giovanni Traverso and Robert Langer explain the gastrointestinal frontier.

Gastrointestinal motility disorders affect over 20% of the population, yet current therapies provide limited relief. Here, the authors show that in a swine model a closed-loop GI neuroprosthesis restores peristalsis and enhances metabolic responses via targeted electrical and chemical stimulation

Preventing endosomal damage sensing or using lipids that create reparable endosomal holes reduces inflammation caused by RNA–lipid nanoparticles while enabling high RNA expression.

Radiation-therapy-induced DNA damage in oral and rectal epithelial cells can be reduced via the nanoparticle-mediated local delivery of messenger RNA encoding for a damage-suppressor protein found in radiation-resistant tardigrades.

A remora-inspired mechanical underwater adhesive device adheres securely to a range of soft substrates and maintains performance under extreme pH and moisture conditions, with potential applications in biosensing and drug delivery.

Polygenic scores for body mass index and obesity constructed using data from 5 million people with different ancestries were associated with distinct weight gain trajectories from early childhood to adulthood.

An ingestible electronic device can record biopotential electrical signals from the gastric environment—including the gastric slow wave, respiration signal and heart signal—and can monitor slow wave activity in freely moving and feeding animals.

Biologics are delivered by a pill that pricks the stomach wall.

Wireless ingestible microdevices can be tracked through the gastrointestinal tract of large animals in real time and with millimetre-scale spatial resolution by generating three-dimensional magnetic field gradients in the gastrointestinal field-of-view using high-efficiency planar electromagnetic coils, which encode each spatial point with a distinct magnetic field magnitude.

This study reports on self-aggregating injectable microcrystals for administering long-acting drug implants via low-profile needles, a key factor in patient adoption. Microcrystal self-aggregation is engineered through a solvent exchange process to form depots with minimal polymer excipient, demonstrating enhanced long-term release of a model contraceptive drug in rodents.

This Review discusses how continuous monitoring technologies can enable early symptom detection, disease recurrence tracking and treatment response assessment, and how these technologies are being integrated into clinical practice.

Poor adherence to daily antiretrovirals can significantly affect treatment efficacy, but oral long-acting antiretrovirals are currently lacking. Here, the authors develop a once-weekly oral dosage form for anti-HIV drugs, assess its pharmacokinetics in pigs, and model its impact on viral resistance and disease epidemics.

No method exists for real-time evaluation of the status of spinal implants. Here, the authors developed a bio-adhesive metal detector array (BioMDA) that provides a wearable, non-invasive solution for positional analyses of osseous implants within the spine.

Existing ingestible electronics suffer from poor tissue contact, short dwell time, and limited battery life. Here, the authors report an ingestible, battery- free, and tissue-adhering robotic interface for non-invasive and chronic electrostimulation of the gut.

A machine-learning model trained on interactions between oral drugs and intestinal drug transporters obtained by modulating their expression in intact porcine tissue can be used to predict drug–transporter and drug–drug interactions.

Sequential drinks of crosslinker and polymer solutions form a tough hydrogel in the stomach, enabling delivery of drugs and biologics in this harsh chemical environment.

Reduced glomerular filtration rate (eGFR) is a hallmark of chronic kidney disease. Here, Pattaro et al. conduct a meta-analysis to discover several new loci associated with variation in eGFR and find that genes associated with eGFR loci often encode proteins potentially related to kidney development.

A robotically handled culture system using porcine gastrointestinal tissue explants for the high-throughput interrogation of the gastrointestinal tract predicts the absorption of oral drugs in the human gut better than Caco-2 Transwells.

Buckling kirigami structures applied to footwear outsoles generate higher friction forces transversally to the direction of movement.

A high-throughput screen of substances generally recognized as safe identifies species-specific materials that stabilize live microbial therapeutics as powders, making them robust to pharmaceutical manufacturing workflows.

In this Review, Chu and Traverso provide an overview of gastrointestinal-based drug delivery, discussing conventional delivery methods and challenges posed by the gastrointestinal tract as a drug delivery environment, as well as emerging technologies.

An inexpensive knotted catheter-like device made of a piezoresistive elastic silicone–liquid-metal composite performs comparably to commercial manometry devices for the sensing of gastrointestinal motility in anaesthetized pigs.

Self-assembly of small drugs with organic dyes represents a facile route to synthesize nanoparticles with high drug-loading capability. Here the authors combine a machine learning approach with high-throughput experimental validation to identify which combinations of drugs and excipient lead to successful nanoparticle formation and characterize the therapeutic efficacy of two of them in vitro and in animal models.

Polymeric nanomaterials have a rich history of applications in the selective delivery of small-molecule drugs to their biological targets. This Review discusses the evolution of drug delivery using such polymers and explores how these approaches have evolved in parallel with the ability to prepare ever more architecturally complex macromolecular structures.

Inbreeding depression has been observed in many different species, but in humans a systematic analysis has been difficult so far. Here, analysing more than 1.3 million individuals, the authors show that a genomic inbreeding coefficient (FROH) is associated with disadvantageous outcomes in 32 out of 100 traits tested.

A biocompatible, energy-harvesting electrochemical cell delivers power to a wireless sensor for an average of 6.1 days of temperature measurements in the gastrointestinal tract of pigs.

Anna Köttgen and colleagues report genome-wide association studies for serum urate in over 140,000 individuals from the Global Urate Genetics Consortium (GUGC). They identify 18 loci newly associated with serum urate concentrations and confirm 10 known loci, characterize their associations with gout and include a network analysis suggesting a role for inhibins-activins pathways in regulating urate homeostasis.

High swelling ratio, speed and long term robustness tend not coexist in hydrogels which limits their use in devices. Here, the authors introduce a pufferfish-inspired hydrogel device ingested as a standard-sized pill, swells rapidly and maintains robustness under repeated mechanical loads in the stomach.

A supramolecular elastic polymer that is stable in the acidic environment of the stomach but dissolves in the neutral-pH environment of the intestines is shown to function as a safe gastric-retentive device in pigs.

A kirigami-inspired stent-based system has been developed for extended local drug delivery to the gastrointestinal and respiratory tracts as well as the vascular system.

This study shows that the transcriptional repressor Otx2 negatively regulates the expression of the dopamine transporter DAT in dopaminergic neurons of the ventral tegmental area (VTA). Elevated Otx2 confers resistance to the neurotoxin MPTP and may explain why a subpopulation of VTA neurons resist degeneration in Parkinson's disease.

An ingestible, flexible piezoelectric sensor that senses mechanical deformations in the gastric cavity allows for the monitoring of ingestion states in the gastrointestinal tract of pigs.

The use of drug delivery systems for the gastrointestinal tract has been faced with a number of drawbacks related to their prolonged use. Here, the authors develop a drug-loaded hydrogel with high strength to withstand long-term gastrointestinal motility and can be triggered to dissolve on demand.

Microchips embedding a magnetic sensor and a radiofrequency transmitter can be localized in the body of a mouse at submillimetre resolution when under a magnetic field.

DigiONE is a pilot European learning health system in precision oncology that aims to identify optimal cancer treatments by learning from every patient, not just those in trials, through privacy-preserving interrogation of their standardized routine electronic health records.

A luminal unfolding microneedle injector device (LUMI) is engineered as a custom capsule capable of efficient biologic macromolecular drug delivery into the bloodstream via selective deployment within the gastrointestinal tract.

Genetic variants in ionotropic glutamate receptors have been implicated in neurodevelopmental disorders. Here, the authors report heterozygous de novo mutations in the GRIA2 gene in 28 individuals with intellectual disability and neurodevelopmental abnormalities associated with reduced Ca²⁺ transport and AMPAR currents.”

The alternative splicing factor Nova2 is best known for its pivotal function in the brain. Giampietro et al. reveal an important role for Nova2 in the regulation of alternative splicing of transcripts in the vascular endothelium that are crucial for the maintenance of endothelial cell polarity and vessel lumen formation in zebrafish.

Pancreatic islet transplantation stands to enable patients with type 1 diabetes to become insulin-independent. However, the number of islets required to achieve insulin independence is not yet well-defined and depends on the transplantation approach. Here, we contextualize a ‘rule of thumb’ estimate of the islet quantities required for transplantation, and discuss the estimate’s practical implications.

An analysis of 16 health-related quantitative traits in approximately 350,000 individuals reveals statistically significant associations between genome-wide homozygosity and four complex traits (height, lung function, cognitive ability and educational attainment); in each case increased homozygosity associates with a decreased trait value, but no evidence was seen of an influence on blood pressure, cholesterol, or ten other cardio-metabolic traits.

Immunotherapies, predominantly immune-checkpoint inhibitors and chimaeric antigen receptor T cells, have transformed oncology. Nonetheless, these systemically administered agents have several limitations, including the risk of off-target toxicities and a lack of activity owing to an inability to overcome an immunosuppressive tumour microenvironment (TME). In this Review, the authors describe the potential to overcome these challenges using functionalized nanomaterials that are designed to release a wide range of immunotherapeutic cargoes in response to specific TME characteristics, including hypoxia, differences in pH, the presence of specific enzymes, reactive oxygen species and/or high levels of extracellular ATP.