Cervical cancer is a leading cause of cancer-related mortality worldwide, killing over 300,000 women annually. Lack of resources to perform screening and treatment of cervical cancer in low- and middle-income countries (LMICs) as well as the stigma associated with screening has led to high mortality rates in these regions. Specifically, the speculum-a duck bill-shaped device used to open the vaginal canal for visualization of the cervix by a clinician-does not always provide a clear line of sight to the cervix and can cause patient discomfort due to the concentrated stress it exerts on the vaginal canal. To overcome these barriers, we developed a low-cost screening device for use in LMIC settings that enables better visualization of the cervix at low cervical angles and exerts less pressure on the vaginal walls compared to a speculum in finite element (FE) models.
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 theranostics. Here, we report the development of an electroadhesive hydrogel interface for robust and prolonged mucosal retention after electrical activation (e-GLUE). The e-GLUE device is composed of cationic polymers interpenetrated within a tough hydrogel matrix. An e-GLUE electrode design eliminated the need for invasive submucosal placement of ground electrodes for electrical stimulation during endoscopic delivery. With an electrical stimulation treatment of about 1 minute, the cationic polymers diffuse and interact with polyanionic proteins that have a relatively slow cellular turnover rate in the deep mucosal tissue. This mucosal adhesion mechanism increased the adhesion energy of hydrogels on the mucosa by up to 30-fold and enabled in vivo gastric retention of e-GLUE devices in a pig stomach for up to 30 days. The adhesion strength was modulated by polycationic chain length, electrical stimulation time, gel thickness, cross-linking density, voltage amplitude, polycation concentration, and perimeter-to-area ratio of the electrode assembly. In porcine studies, e-GLUE demonstrated rapid mucosal adhesion in the presence of luminal fluid and mucus exposure. In proof-of-concept studies, we demonstrated e-GLUE applications for mucosal hemostasis, sustained local delivery of therapeutics, and intimate biosensing in the gastrointestinal tract, which is an ongoing clinical challenge for commercially available alternatives, such as endoclips and mucoadhesive. The e-GLUE platform could enable theranostic applications across a range of digestive diseases, including recurrent gastrointestinal bleeding and inflammatory bowel disease.
Myocardial infarction (MI) is a major global health challenge. Surgical interventions address the acute phase but often fail to support long-term recovery. Sequential post-operative drug delivery offers promise but is constrained by release methods. Here, we developed TIMED (temporal intervention with microparticle encapsulation and delivery), a polymeric device enabling programmed sequential release through spatially patterned microparticles in a tough hydrogel matrix. TIMED demonstrated excellent mechanical performance and biocompatibility for long-term implantation and retained strong stability after storage. A sequential dosing regimen aligned with the innate post-MI response was first validated in hiPSC-derived cardiac tissues, where it enhanced cell viability and vascularization while reducing collagen deposition. In vivo, delivery via the TIMED improved survival, reduced injury markers and infarct size, and enhanced cardiac output, outperforming equivalent i.v. dosing. This work establishes a first-of-its-kind cardiac implantable polymeric platform with modular sequential release and provides a framework for programmed multi-dosing across diverse applications.
Electronic capsules have emerged as a transformative technology in the diagnosis of gastrointestinal (GI) diseases, achieving remarkable progress over the past three decades. Although existing capsule systems based on the monitoring of physical parameters have been successfully translated into clinical practice, they remain limited by insufficient disease specificity, constraining their utility for precision diagnosis of GI disorders. Next-generation electronic capsules, by incorporating biochemical biomarker-sensing capabilities, are poised to significantly enhance diagnostic accuracy and accelerate the transition of the field toward molecular-level, in situ detection. Moreover, the growing recognition of the gut microbiota as a critical predictor of systemic diseases positions electronic capsules as a revolutionary platform for dynamic, whole-body health assessment. This review systematically explores the applications and limitations of electronic capsules in monitoring physical parameters and summarizes recent technological advances in biochemical biomarker detection, highlighting the transformative role of electronic capsules in precision medicine and their prospects.
Soft robotic grippers possess high structural compliance and adaptability, allowing them to grasp objects with unknown and irregular shapes and sizes. To enable more dexterous manipulation, soft sensors that are similar in mechanical properties to common elastomer materials are desired to be integrated into soft grippers. In this paper, we develop ionic hydrogel-based strain and tactile sensors and integrate these sensors into a three-finger soft gripper for learning-based object recognition and force-controlled grasping. Such hydrogel-based sensors have excellent conductivity, high stretchability and toughness, good ambient stability, and unique antifreezing property; they can be readily attached to a soft gripper at desired locations for strain and tactile sensing. By using a deep-learning model, the sensory soft gripper is demonstrated to be capable of grasping and recognizing objects at both room and freezing temperatures, and achieving close to 100% recognition accuracy for ten typical objects. Moreover, the capacitive tactile feedback of the gripper is utilized to develop a closed-loop force controller and realize force-controlled grasping of fragile or highly deformable objects. A new slip detection and compensation strategy is also proposed and validated for the sensory gripper for adjusting the grasping force in real time upon detecting slippage. Note to Practitioners-The multimodal sensation of a soft robotic gripper could enrich its grasping functionalities and improve its manipulation performance. This research integrates novel antifreezing ionic hydrogel-based strain and tactile sensors into a three-finger soft robotic gripper for learning-based object recognition and force-controlled grasping. Constructed from a highly stretchable, ambient-stable, and antifreezing ionic hydrogel, the strain and tactile sensors can be readily integrated at the desired locations on the soft gripper, and can reliably operate at both ambient and freezing temperatures with excellent mechanical and electrical properties. Based on the feedback of the strain and tactile sensors, a deep learning model is employed to enable high-accuracy object recognition while grasping, which can be useful for manipulation in vision-free environments. Closed-loop force control and slip compensation strategies are also demonstrated for reliably grasping fragile/deformable objects and handling slip events during the manipulation of heavy objects. The sensory soft gripper and the associated object recognition and force control methods could find practical applications in a variety of robotic manipulation tasks.
Correction for 'Kirigami-enabled stretchable laser-induced graphene heaters for wearable thermotherapy' by Junyu Chen et al., Mater. Horiz., 2024, 11, 2010-2020, https://doi.org/10.1039/D3MH01884A.
Engineered bacteria are increasingly recognized as sustained and intelligent sources for sensing and therapeutics due to their unique capabilities such as in situ multiplication, tissue targeting, and genetic editability. However, the clinical applications of these living agents are hindered by the ineffective immunoisolation, residency, and removal against the complex and dynamic in vivo environment. Existing approaches focus on surface decoration and encapsulation of engineered bacteria, or "microencapsulation,"but there are limits to what can be achieved with modifications of bacteria themselves. An emerging strategy combines millimeter- to centimeterscale engineered devices and systems with bacteria, or "macroencapsulation,"offering unique advantages such as extending the in vivo lifetime and engraftment of bacteria, enhancing immunoisolation, and enabling real -time signal readouts via wireless electronic technologies. In this review, the design rationales for macroencapsulated bacteria toward in vivo applications are discussed, and examples in bacterial devices for transdermal and oral applications are highlighted. Since the gastrointestinal tract represents a major site for engineered bacteria, we also summarize and compare various strategies for synthetic engraftment of orally administered encapsulated bacteria.
Stretchable later-induced graphene (LIG) heaters with kirigami structures are produced via laser engraving/cutting for wearable thermotherapy. Such a heater has a rapid electrothermal response and robust performance for on-body use.
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. 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.
Gastrointestinal (GI) neuromuscular diseases can be challenging to diagnose due to inadequate profiling technologies that are unable to pinpoint underlying pathology. We introduce a luminal electrophysiological neuroprofiling system (LENS). This tool uses high-resolution electromyographic data to capture motility of the GI tract, grade neurogenic deficiencies overtime, and elucidate motility patterns. Through the development of analytical metrics, we determine "neuroprofiles"for various enteric neuropathies in models of dysmotility, sphincter dysfunction, and aganglionosis. The LENS differentiates between aganglionic and ganglionic regions based on the contractile rate (p <0.0001) and root-mean-square amplitude (p < 0.0001). In mice with hypomotility, metrics like area under the curve and peak height of the Fourier transformation of the electrophysiological signal in the frequency ranges of 0-20 and 115-135 Hz were significant differentiators, with up to 89% accuracy of classification between pathologic and normal motility. Such a platform can enable realization of specific diagnoses and quantify their severity.
Correction for 'Kirigami-enabled stretchable laser-induced graphene heaters for wearable thermotherapy' by Junyu Chen et al., Mater. Horiz., 2024, 11, 2010-2020, https://doi.org/10.1039/D3MH01884A.
The dura mater is the final barrier against cerebrospinal fluid leakage and plays a crucial role in protecting and supporting the brain and spinal cord. Head trauma, tumor resection and other traumas damage it, requiring artificial dura mater for repair. However, surgical tears are often unavoidable. To address these issues, the ideal artificial dura mater should have biocompatibility, anti-leakage, and self-healing properties. Herein, this work has used biocompatible polycaprolactone diol as the soft segment and introduced dynamic disulfide bonds into the hard segment, achieving a multifunctional polyurethane (LSPU-2), which integrated the above mentioned properties required in surgery. In particular, LSPU-2 matches the mechanical properties of the dura mater and the biocompatibility tests with neuronal cells demonstrate extremely low cytotoxicity and do not cause any negative skin lesions. In addition, the anti-leakage properties of the LSPU-2 are confirmed by the water permeability tester and the 900 mm H2 O static pressure test with artificial cerebrospinal fluid. Due to the disulfide bond exchange and molecular chain mobility, LSPU-2 could be completely self-healed within 115 min at human body temperature. Thus, LSPU-2 comprises one of the most promising potential artificial dura materials, which is essential for the advancement of artificial dura mater and brain surgery.
Vaccines provide substantial safety against infectious diseases, saving millions of lives each year. The recent COVID-19 pandemic highlighted the importance of vaccination in providing mass-scale immunization against outbreaks. However, the delivery of vaccines imposes a unique set of challenges due to their large molecular size and low room temperature stability. Advanced biomaterials and delivery systems such as nano- and mciro-scale carriers are becoming critical components for successful vaccine development. In this review, we provide an updated overview of recent advances in the development of nano- and micro-scale carriers for controlled delivery of vaccines, focusing on carriers compatible with nucleic acid-based vaccines and therapeutics that emerged amid the recent pandemic. We start by detailing nano-scale delivery systems, focusing on nanoparticles, then move on to microscale systems including hydrogels, microparticles, and 3D printed microneedle patches. Additionally, we delve into emerging methods that move beyond traditional needle-based applications utilizing innovative delivery systems. Future challenges for clinical translation and manufacturing in this rapidly advancing field are also discussed.
Glioblastoma (GBM) is the most common and aggressive primary brain cancer. Despite multimodal treatment including surgery, radiotherapy, and chemotherapy, median patient survival has remained at ~15 months for decades. This situation demands an outside-the-box treatment approach. Using magnetic carbon nanotubes (mCNTs) and precision magnetic field control, we report a mechanical approach to treat chemoresistant GBM. We show that GBM cells internalize mCNTs, the mobilization of which by rotating magnetic field results in cell death. Spatiotemporally controlled mobilization of intratumorally delivered mCNTs suppresses GBM growth in vivo. Functionalization of mCNTs with anti-CD44 antibody, which recognizes GBM cell surface–enriched antigen CD44, increases mCNT recognition of cancer cells, prolongs mCNT enrichment within the tumor, and enhances therapeutic efficacy. Using mouse models of GBM with upfront or therapy-induced resistance to temozolomide, we show that mCNT treatment is effective in treating chemoresistant GBM. Together, we establish mCNT-based mechanical nanosurgery as a treatment option for GBM.
Gastrointestinal (GI) residence systems that integrate functions such as sensing, stimulation, and drug delivery hold promise for intervening in and treating chronic GI conditions. However, extending device retention beyond 24 h remains challenging. In this review, we present current engineering approaches that extend GI retention across various spatiotemporal scales. We then summarize their applications in drug delivery, sensing, and stimulation within the GI tract that benefit from prolonged device residency. Finally, we outline emerging strategies that leverage breakthroughs in materials, mechanics, and robotics to enable the development of next-generation GI residence systems. This review aims to present a future of GI residence systems that enable long-term, autonomous, and closed-loop therapies and are thus indispensable in next-generation healthcare.
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 e lectroadhesive hydro g e l interface for robust and prolonged m u cosal r e tention 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.### Competing Interest StatementComplete details of all relationships for-profit and not for-profit for G. T. can be found at the following link: [http://www.dropbox.com/sh/szi7vnr4a2ajb56/AABs5N5i0q9AfT1IqIJAE-T5a?dl=0][1]. Complete details for R. S. L. can be found at the following link: [http://www.dropbox.com/s/yc3xqb5s8s94v7x/Rev%20Langer%20COI.pdf?dl=0][2]. The remaining authors declare no competing financial interests. [1]: https://www.dropbox.com/sh/szi7vnr4a2ajb56/AABs5N5i0q9AfT1IqIJAE-T5a?dl=0 [2]: https://www.dropbox.com/s/yc3xqb5s8s94v7x/Rev%20Langer%20COI.pdf?dl=0
The nanofibrillated cellulose paper (nanocellulose paper or nanopaper), which is flexible, transparent, ultrasmooth, and biodegradable, has emerged as a new substrate material for the next generation of paper‐based flexible electronics. Herein a visible light‐induced printing technique for depositing highly conductive silver (Ag) patterns on nanopaper is reported. The optical Ag printing process is simple to implement at room temperature and only requires nontoxic, low‐cost aqueous chemical solutions and an inexpensive light projection setup. The abundant carboxyl groups on the nanopaper enable efficient absorption of Ag+ions on the nanopaper surface for light‐induced reduction of Ag+into a thin film of densely packed silver nanoparticles (AgNPs). Chemical annealing of the deposited AgNPs further enhances the conductivity of the printed Ag patterns. The mechanical and electrical properties of the printed Ag patterns on nanopaper are characterized, and the application of the optical Ag printing technique fabricating the nanopaper‐based flexible circuits and electrochemical biosensors is also demonstrated. The optical printing technique will enable new designs and applications of nanopaper‐based flexible electronics.
The surface mucosa that lines many of our organs houses myriad biometric signals and, therefore, has great potential as a sensor–tissue interface for high-fidelity and long-term biosensing. However, progress is still nascent for mucosa-interfacing electronics owing to challenges with establishing robust sensor–tissue interfaces; device localization, retention and removal; and power and data transfer. This is in sharp contrast to the rapidly advancing field of skin-interfacing electronics, which are replacing traditional hospital visits with minimally invasive, real-time, continuous and untethered biosensing. This Review aims to bridge the gap between skin-interfacing electronics and mucosa-interfacing electronics systems through a comparison of the properties and functions of the skin and internal mucosal surfaces. The major physiological signals accessible through mucosa-lined organs are surveyed and design considerations for the next generation of mucosa-interfacing electronics are outlined based on state-of-the-art developments in bio-integrated electronics. With this Review, we aim to inspire hardware solutions that can serve as a foundation for developing personalized biosensing from the mucosa, a relatively uncharted field with great scientific and clinical potential. The surface mucosa that lines many of our organs hosts a diverse set of biometric signals. This Review compares present skin-interfacing and mucosa-interfacing electronics to inspire hardware solutions for developing devices for personalized biosensing from the mucosa.
The rapid development of stretchable electronics and soft robotics requires a sustainable power source that can match their mechanical stretchability in various working environments. Ionic hydrogel-based soft triboelectric nanogenerators (TENGs) show great promise for those application scenarios. However, ionic hydrogel-based TENGs suffer from the freezing issue under subzero temperatures. In this study, a low-cost, highly stretchable, and antifreezing ionic triboelectric nanogenerator (iTENG) is designed to involve a dielectric elastomer and a freeze-tolerant ionic hydrogel as the electrification layer and the electrode, respectively. The iTENG design achieves a unique combination of merits such as robust hydrogel-elastomer bonding, high stretchability (300%), and excellent tolerance of extremely low temperature (down to -53 degrees C). Because of the reliable interfacial bonding, the iTENG shows a good mechanical durability under different stretching conditions. The iTENG can harvest mechanical energies from various human motions and can also serve as a self-powered wearable sensor in both regular and extremely cold environments. The stretchable iTENG overcomes the strain-induced performance degradation of existing stretchable materials with percolated conductive fillers and the water freezing-induced degradation of conductive ionic hydrogels, providing a feasible design of stretchable and sustainable power sources for stretchable electronics and soft robotics operating in harsh environments.