Latest Articles
Biomedical engineering
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Nature
Slipknot-gauged mechanical transmission and robotic operation
Mechanical transmission is essential in force-related activities ranging from the daily tying of shoe laces1to sophisticated surgical2and robotic operations3,4. Modern machines and robots typically use complex electronic devices designed to sense and limit force5, some of which still face challenges when operating space is limited (for example, in minimally invasive surgeries)6or when resources are scarce (for example, operations in remote areas without electricity). Here we describe an alternative slipknot-based mechanical transmission mechanism to control the intelligent operation of both human and robotic systems. Through topological design, slipknot tying and release can encode and deliver force with a consistency of 95.4% in repeating operations, which circumvents the need for additional sensors and controllers. When applied to surgical repair, this mechanism helped inexperienced surgeons to improve their knotting-force precision by 121%, enabling them to perform surgical knots as good as those of experienced surgeons. Moreover, blood supply and tissue healing after surgery were improved. The mechano-intelligence exhibited in slipknots may inspire investigations of knotted structures across multiple length scales. This slipknot-gauged mechanical transmission strategy can be widely deployed, opening up opportunities for resource-limited healthcare, science education and field exploration.
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Nature
A skin-permeable polymer for non-invasive transdermal insulin delivery
Non-invasive skin permeation is widely used for convenient transdermal delivery of small-molecule therapeutics (less than 500 Da) with appropriate hydrophobicities1. However, it has long been deemed infeasible for large molecules—particularly polymers, proteins and peptides2,3—due to the formidable barrier posed by the skin structure. Here we show that the fast skin-permeable polyzwitterion poly[2-(N-oxide-N,N-dimethylamino)ethyl methacrylate] (OP) can efficiently penetrate the stratum corneum, viable epidermis and dermis into circulation. OP is protonated to be cationic and is therefore enriched in the acidic sebum and paracellular stratum corneum lipids containing fatty acids, and subsequently diffuses through the intercorneocyte lipid lamella. Beneath the stratum corneum, at the normal physiological pH, OP becomes a neutral polyzwitterion, ‘hopping’ on cell membranes, enabling its efficient migration through the epidermis and dermis and ultimately entering dermal lymphatic vessels and systemic circulation. As a result, OP-conjugated insulin efficiently permeates through the skin into the blood circulation; transdermal administration of OP-conjugated insulin at a dose of 116 U kg−1into mice with type 1 diabetes quickly lowers their blood glucose levels to the normal range, and a transdermal dose of 29 U kg−1normalizes the blood glucose levels of diabetic minipigs. Thus, the skin-permeable polymer may enable non-invasive transdermal delivery of insulin, relieving patients with diabetes from subcutaneous injections and potentially facilitating patient-friendly use of other protein- and peptide-based therapeutics through transdermal delivery.
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Nature
High-density soft bioelectronic fibres for multimodal sensing and stimulation
There is an increasing demand for multimodal sensing and stimulation bioelectronic fibres for both research and clinical applications1,2. However, existing fibres suffer from high rigidity, low component layout precision, limited functionality and low density of active components. These limitations arise from the challenge of integrating many components into one-dimensional fibre devices, especially owing to the incompatibility of conventional microfabrication methods (for example, photolithography) with curved, thin and long fibre structures2. As a result, limited applications have been demonstrated so far. Here we use ‘spiral transformation’ to convert two-dimensional thin films containing microfabricated devices into one-dimensional soft fibres. This approach allows for the fabrication of high-density multimodal soft bioelectronic fibres, termed Spiral-NeuroString (S-NeuroString), while enabling precise control on the longitudinal, angular and radial positioning and distribution of the functional components. Taking advantage of the biocompatibility of our soft fibres with the dynamic and soft gastrointestinal system, we proceed to show the feasibility of our S-NeuroString for post-operative multimodal continuous motility mapping and tissue stimulation in awake pigs. We further demonstrate multi-channel single-unit electrical recording in mouse brain for up to 4 months, and a fabrication capability to produce 1,280 channels within a 230-μm-diameter soft fibre. Our soft bioelectronic fibres offer a powerful platform for minimally invasive implantable electronics, where diverse sensing and stimulation functionalities can be effectively integrated.
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Nature
A movable long-term implantable soft microfibre for dynamic bioelectronics
Long-term implantable bioelectronics offer a powerful means to evaluate the function of the nervous system and serve as effective human–machine interfaces1,2,3. Here, inspired by earthworms, we introduce NeuroWorm—a soft, stretchable and movable fibre sensor designed for bioelectronic interface. Our approach involves rolling to transform 2D bioelectronic devices into 1D NeuroWorm, creating a multifunctional microfibre that houses longitudinally distributed electrode arrays for both bioelectrical and biomechanical monitoring. NeuroWorm effectively records high-quality spatio-temporal signals in situ while steerably advancing within the brain or on the muscle as needed. This allows for the dynamic targeting and shifting of desired monitoring sites. Implanted in muscle through a tiny incision, NeuroWorm provides stable bioelectrical monitoring in rats for more than 43 weeks. Even after 54 weeks of implantation in muscle, fibroblast encapsulation around the fibre remains negligible. Our NeuroWorm represents a platform that promotes a substantial advance in bioelectronics—from an immobile probe fixed in place to active, intelligent and living devices for long-term, minimally invasive and mobile evaluation of the nervous system.
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Nature
Adaptive and context-aware volumetric printing
We introduce Generative, Adaptive, Context-Aware 3D Printing (GRACE), a new approach combining 3D imaging, computer vision and parametric modelling to create tailored, context-aware geometries using volumetric additive manufacturing. GRACE rapidly and automatically generates complex structures capable of conforming directly around features ranging from cellular to macroscopic scales with minimal user intervention. Here we demonstrate its versatility in applications ranging from synthetic objects to biofabrication, including adaptive vascular-like geometries around cell-laden bioinks, resulting in improved functionality. GRACE also enables precise alignment of sequential prints, as well as the detection and overprinting of opaque surfaces through shadow correction. Compatible with various printing modalities1,2,3,4, GRACE transcends traditional additive manufacturing limitations in automating overprinting and adapting the printed designs to the content of the printable material. This opens new possibilities in tissue engineering and regenerative medicine.