Yuan Yao

Soft actuators that integrate biodegradability, responsiveness to human-safe stimuli, and high actuation performance are highly desirable for next-generation biomedical devices. However, current systems fail to realize these attributes within a single platform. Here, we propose a microfibrillated cellulose (MFC)–based soft actuator incorporating a poly(ethylene glycol) (PEG) network to suppress crystallinity and ionic liquid (IL) aggregation. This design enhances ionic conductivity, forms abundant ion transport channels, and reduces interfacial resistance. Operated at 1 volt, the actuator achieves a record-high energy density of 64.4 kilojoules per cubic meter and the fastest response time of 1 second among reported ionic electroactive polymers (IEAPs) under the same conditions. Such materials are biocompatible and biodegradable in various physiological environments. Device-level demonstrations show that an actuation-enabled sciatic nerve cuff enables high-fidelity signal transmission in vitro with a signal-to-noise ratio of 40 decibels and stable real-time in vivo neural recording with evoked responses of up to ~150 microvolts, supporting minimally invasive bioelectronic interfacing.

Implantable hydrogel bioelectronics are promising candidates for seamlessly bridging biological systems with intelligent devices. However, sustaining stable communication between hydrogel electronics and biological systems in complex physiological environments remains a critical challenge, primarily due to the swelling-induced degradation of mechanical properties of hydrogel encapsulation and reduced electrical performance of the conductive networks. To address this, we developed a micelle-assembly approach to synthesize soft and highly stretchable hydrogels with swelling-resistant performance. Moreover, these hydrogels show alleviated foreign body reactions during long-term implantation, serving as valuable implant materials. Through embedded 3D printing technology, we engineered ultrasoft (~ 40 kPa) and stretchable (over 1,000%) hydrogel electronics with unprecedented conductivity retention in aqueous environment – conductivity over 9,000 S cm-1 post-printing and 4,000 S cm-1 even after swollen. We further printed three different types of invasive implants, including brain-computer interfaces, implantable wirelessly-powered optoelectronics and sciatic nerve stimulators. These devices can either perceive physiological signals or receive electronic orders and respond accordingly with extraordinary robustness and longevity in vivo. We believe that such technological advances hold great promise for the development of human-computer interfaces.

Stimuli-triggered simultaneous shape-morphing and color-changing can be found in many natural species. Developing synthetic materials and systems with these bioinspired properties could potentially transform a range of applications from autonomous soft robots to tissue engineering. Here, the design and additive manufacturing of a new lanthanide-ion coordinated supramolecular hydrogel are reported, whose luminescence and opacity can be dynamically tuned in re-sponse to different humidity or hydration/dehydration. The fluorescent color tuning is provided by the competing effect between nonconjugated chromophores and the dynamically coordinated Eu3+ ions, while the opacity changing is resulted from the phase separation/dissolution of the neutralized zwitterionic polymers in dehydrated/hydrated state. To demonstrate camouflageable soft actuators, multimaterial direct ink writing (DIW) is harnessed to manufacture hydro-gel-based actuators with controlled shape, luminescence and opacity change on demand.

Heavy‐metal‐free fluorescent nanoparticles with high photostability and low toxicity are highly desirable as imaging probes for biological applications. Here, a novel synthetic strategy to prepare ultrabright multi‐carbon dot cross‐linked PEI particles, namely CDs@PEI, through self‐assembly of hydrophobically modified PEI and in situ generations of carbon dots within residual monomer‐swollen micelles is reported. The resulting particles consist of numerous carbon dots, which are individually and homogeneously embedded within the PEI network, and have an average hydrodynamic diameter of approximately 100 nm with ζ‐potential above +35 mV. The CDs@PEI particles possess the synergistic effect of photoluminescent carbon dot and crosslink‐enhanced emission of PEI, giving the particles superior optical properties such as high fluorescence quantum yield (up to 66%) in the aqueous system, excitation‐dependent emission phenomenon, stable fluorescence in a wide pH range, and resistance to photobleaching.

Bone morphogenetic protein (BMP)-9 has been associated with insulin resistance and type 2 diabetes mellitus. However, methods for delivering exogenous BMP-9 genes in vivo are lacking. In this study, we developed a gene delivery system using polyethyleneimine (PEI)-based core–shell nanoparticles (PCNs) as gene delivery carriers, and investigated the effectiveness and safety for delivery of the shBMP-9 gene. PCNs possessed a well-defined core–shell nanostructure with hydrophobic polymer cores and dense PEI shells of uniform particle size and highly positively charged surfaces. In vitro evaluation suggested that PCNs had high loading capacity for exogenous genes and low cytotoxicity toward hepatocytes. The transfection efficiency of PCNs/pENTR-shBMP9 complexes was higher than that of commercial lipofectamine 2000/shBMP9. In vivo studies showed that PCNs/pENTR-shBMP9 transfection led to a significant decrease in hepatic BMP9 expression compared with pENTR-shBMP9 transfection. Under high fat diet (HFD) feeding, PCNs/pENTR-shBMP9 mice exhibited aggravated glucose and insulin tolerance. At a molecular level, PCNs/pENTR-shBMP9 mice displayed elevated PEPCK protein levels and lower levels of InsR and Akt phosphorylation than pENTR-shBMP9 mice. These results suggest that the biological effects of PCNs/pENTR-shBMP9 in vivo are much more effective than those of pENTR-shBMP9. Therefore, the polyethyleneimine (PEI)-based core–shell nanoparticle can be applied as promising nanocarriers for effective and safe gene delivery.

A scalable synthesis of magnetic core–shell nanocomposite particles, acting as a novel class of magnetic resonance (MR) contrast agents, has been developed. Each nanocomposite particle consists of a biocompatible chitosan shell and a poly(methyl methacrylate) (PMMA) core where multiple aggregated γ‐Fe₂O₃ nanoparticles are confined within the hydrophobic core. Properties of the nanocomposite particles including their chemical structure, particle size, size distribution, and morphology, as well as crystallinity of the magnetic nanoparticles and magnetic properties were systematically characterized. Their potential application as an MR contrast agent has been evaluated. Results show that the nanocomposite particles have good stability in biological media and very low cytotoxicity in both L929 mouse fibroblasts (normal cells) and HeLa cells (cervical cancer cells). They also exhibited excellent MR imaging performance with a T₂ relaxivity of up to 364 mM_Fe⁻¹ s⁻¹. An in vivo MR test performed on a naked mouse bearing breast tumor indicates that the nanocomposite particles can localize in both normal liver and tumor tissues. These results suggest that the magnetic core–shell nanocomposite particles are an efficient, inexpensive and safe T₂‐weighted MR contrast agent for both liver and tumor MR imaging in cancer therapy.

Efficient and targeted delivery approach to transfer exogenous genes into macrophages is still a great challenge. Current gene delivery methods often result in low cellular uptake efficiency in vivo in some types of cells, especially for the Kupffer cells (KCs). In this article, we demonstrate that amphiphilic core–shell nanoparticles (NPs) consisting of well-defined hydrophobic poly(methyl methacrylate) (PMMA) cores and branched polyethyleneimine (PEI) shells (denoted as [email protected] NPs) are efficient nanocarriers to deliver microRNA (miRNA)-loaded plasmid to the KCs. Average hydrodynamic diameter of [email protected] NPs was 279 nm with a narrow size distribution. The NPs also possessed positive surface charges up to +30 mV in water, thus enabling effective condensation of negatively charged plasmid DNA. Gel electrophoresis assay showed that the resultant [email protected] NPs were able to completely condense miRNA plasmid at a weight ratio of 25:1 (N/P ratio equal to 45:1). The Cell Counting Kit-8 assay and flow cytometry results showed that the [email protected]/miRNA NPs displayed low cytotoxicity and cell apoptosis activity against the KCs. The maximum cell transfection efficiency reached 34.7% after 48 hours, which is much higher than that obtained by using the commercial Lipofectamine™ 2000 (1.7%). Bio-transmission electron microscope observation revealed that the [email protected] NPs were mainly distributed in the cytoplasm of the KCs. Furthermore, when compared to the control groups, the protein expression of target nuclear factor κB P65 was considerably inhibited (P<0.05) both in vitro and in vivo. These results demonstrate that the [email protected] NPs with a unique amphiphilic core–shell nanostructure are promising nanocarriers for delivering miRNA plasmid to KCs.