Nature Biomedical Engineering最新文献

Individuals with compromised cochlear nerves are ineligible for cochlear implants and instead rely on auditory brainstem implants (ABIs). Most users of ABIs experience sound awareness, which aids in lip reading, yet not speech intelligibility. Here we engineered a dual-site (brainstem and cortex) implantable system, scaled to macaque anatomy, for the analysis of auditory perception evoked by electrical stimulation of the cochlear nucleus. A soft multichannel ABI, fabricated using thin-film processing, provided high-resolution auditory percepts, with spatially distinct stimulation sites eliciting cortical responses akin to frequency-specific tuning. Behavioural responses collected over several months were sufficiently precise to distinguish stimulations from adjacent channels. Soft multichannel ABIs may aid the rehabilitation of individuals with profound hearing loss who are ineligible for cochlear implants.

Correction to: Nature Biomedical Engineering https://doi.org/10.1038/s41551-024-01272-w, published online 25 October 2024.

Swelling-associated changes in extracellular matrix (ECM) occur in many pathological conditions involving inflammation or oedema. Here we show that alterations in the proportion of loosely bound water in ECM correlate with changes in ECM elasticity and stress relaxation, owing to the strength of water binding to ECM being primarily governed by osmolality and the electrostatic properties of proteoglycans. By using mechanical testing and small-angle X-ray scattering, as well as magnetic resonance imaging (MRI) to detect changes in loosely bound water, we observed that enhanced water binding manifests as greater resistance to compression (mechanical or osmotic), resulting from increased electrostatic repulsion between negatively charged proteoglycans rather than axial contraction in collagen fibrils. This indicates that electrostatic contributions of proteoglycans regulate elasticity and stress relaxation independently of hydration. Our ex vivo experiments in osmotically modulated tendon elucidate physical causes of MRI signal alterations, in agreement with pilot in vivo MRI of inflammatory Achilles tendinopathy. We suggest that the strength of water binding to ECM regulates cellular niches and can be exploited to enhance MRI-informed diagnostics of swelling-associated tissue pathology.

Conventional implantable electronic sensors for continuous monitoring of internal tissue strains are yet to match the biomechanics of tissues while maintaining biodegradability, biocompatibility and wireless monitoring capability. Here we present a two-dimensional phononic crystal composed of periodic air columns in soft hydrogel, which was named ultrasonic metagel, and we demonstrate its use as implantable sensor for continuous and wireless monitoring of internal tissue strains. The metagel’s deformation shifts its ultrasonic bandgap, which can be wirelessly detected by an external ultrasonic probe. We demonstrate ex vivo the ability of the metagel sensor for monitoring tissue strains on porcine tendon, wounded tissue and heart. In live pigs, we further demonstrate the ability of the metagel to monitor tendon stretching, respiration and heartbeat, working stably during 30 days of implantation, and we loaded the metagel with growth factors to achieve different healing rates in subcutaneous wounds. The metagel results almost completely degraded 12 weeks after implantation. Our finding highlights the clinical potential of the ultrasonic sensor for tendon rehabilitation monitoring and drug delivery efficacy evaluation.

Correction to: Nature Biomedical Engineering https://doi.org/10.1038/s41551-018-0231-0, published online 23 April 2018.

Antibody conjugates are the foundation of a wide range of diagnostic and therapeutic applications. Although many antibody-conjugation techniques are robust and efficient, obtaining homogeneous multimeric conjugation products remains challenging. Here we report a modular and versatile technique for the site-directed multivalent conjugation of antibodies via the small-protein ubiquitin. Specifically, multiple ubiquitin fusions with antibodies, antibody fragments, nanobodies, peptides or small molecules such as fluorescent dyes can be conjugated to antibodies and nanobodies within 30 min. The technique, which we named ‘ubi-tagging’, allowed us to efficiently generate a bispecific T-cell engager as well as nanobodies conjugated to dendritic-cell-targeted antigens that led to potent T-cell responses. Using both recombinant ubi-tagged proteins and synthetic ubiquitin derivatives allows for the iterative, site-directed and multivalent conjugation of antibodies and nanobodies to a plethora of molecular moieties.