Nanoclay Hydrogel Microspheres with a Sandwich-Like Structure for Complex Tissue Infection Treatment.

Addressing complex tissue infections remains a challenging task because of the lack of effective means, and the limitations of traditional bioantimicrobial materials in single-application scenarios hinder their utility for complex infection sites. Hence, the development of a bioantimicrobial material with broad applicability and potent bactericidal activity is necessary to treat such infections. In this study, a layered lithium magnesium silicate nanoclay (LMS) is used to construct a nanobactericidal platform. This platform exhibits a sandwich-like structure, which is achieved through copper ion modification using a dopamine-mediated metallophenolic network. Moreover, the nanoclay is encapsulated within gelatin methacryloyl (GelMA) hydrogel microspheres for the treatment of complex tissue infections. The results demonstrate that the sandwich-like micro- and nanobactericidal hydrogel microspheres effectively eradicated Staphylococcus aureus (S. aureus) while exhibiting excellent biocompatibility with bone marrow-derived mesenchymal stem cells (BMSCs) and human umbilical vein endothelial cells (HUVECs). Furthermore, the hydrogel microspheres upregulated the expression levels of osteogenic differentiation and angiogenesis-related genes in these cells. In vivo experiments validated the efficacy of sandwich-like micro- and nanobactericidal hydrogel microspheres when injected into deep infected tissues, effectively eliminating bacteria and promoting robust vascular regeneration and tissue repair. Therefore, these innovative sandwich-like micro- and nanobacteriostatic hydrogel microspheres show great potential for treating complex tissue infections.

Untethered Soft Pneumatic Actuators with Embedded Multiple Sensing Capabilities.

Pneumatic soft robot attracts extensive attention because of its own characteristics. It has great application potential in medical and other fields. Although the recent improvement of the soft robot shows great potentials for delicate manipulations, the development of completely untethered pneumatic intelligent soft robots remains challenging. This article introduces a novel type of untethered soft pneumatic actuator with embedded multiple sensing capabilities. The untethered drive of the soft pneumatic actuator is achieved by near-infrared-induced liquid-gas phase transition. In addition, a soft conductive resin was developed to make flexible sensors. Embedded flexible sensors enable bending and temperature sensing of soft actuators. With Digital Light Processing three-dimensional printing, the rapid fabrication of soft actuators and flexible sensors was realized. This article demonstrates the potential of the proposed untethered soft actuators with embedded multiple sensing capabilities as an important contribution to the research of completely untethered intelligent soft robots.

A multifunctional sensor for real-time monitoring and pro-healing of frostbite wounds.

Flexible epidermal sensors based on conductive hydrogels hold great promise for various applications, such as wearable electronics and personal healthcare monitoring. However, the integration of conductive hydrogel epidermal sensors into multiple applications remains challenging. In this study, a multifunctional PAAm/PEG/hydrolyzed keratin (Hereinafter referred to as HK)/MXene conductive hydrogel (PPHM hydrogel) was designed as a high-performance therapeutic all-in-one epidermal sensor. This sensor not only accelerates wound healing but also provides wearable human-computer interaction. The developed sensor possesses highly sensitive sensing properties (Gauge Factor = 4.82 at high strain), strong mechanical tensile properties (capable of achieving a maximum elongation at break of 600 %), rapid self-healing capability, stable self-adhesive capability, biocompatibility, freeze resistance at -20 °C, and adjustable photo-thermal conversion capability. This therapeutic all-in-one sensor can sensitively monitor human movements, enabling the detection of small electrophysiological signals for diagnosing relevant activities and diseases. Furthermore, using a rat frostbite model, we demonstrated that the composite hydrogel sensor can serve as an effective wound dressing to accelerate the healing process. This study serves as a valuable reference for the development of multifunctional flexible epidermal sensors for personal smart health monitoring. STATEMENT OF SIGNIFICANCE: Accelerated wound healing reduces the risk of wound infection, and conductive hydrogel-based sensors can monitor physiological signals. The multifunctional application of conductive hydrogel sensors combined with wound diagnostic and therapeutic capabilities can meet personalized medical requirements for wound healing and sensor monitoring. The aim of this study is to develop a multifunctional hydrogel patch. The multifunctional hydrogel can be assembled into a flexible wearable high-performance diagnostic and therapeutic integrated sensor that can effectively accelerate the healing of frostbite wounds and satisfy the real-time monitoring of multi-application scenarios. We expect that this study will inform efforts to integrate wound therapy and sensor monitoring.

Biohybrid magnetic microrobots: An intriguing and promising platform in biomedicine.

Biohybrid magnetic microrobots (BMMs) have emerged as an exciting class of microrobots and have been considered as a promising platform in biomedicine. Many microorganisms and body's own cells show intriguing properties, such as morphological characteristics, biosafety, and taxis abilities (e.g., chemotaxis, aerotaxis), which have made them attractive for the fabrication of microrobots. For remote controllability and sustainable actuation, magnetic components are usually incorporated onto these biological entities, and other functionalized non-biological components (e.g., therapeutic agents) are also included for specific applications. This review highlights the latest developments in BMMs with a focus on their biomedical applications. It starts by introducing the fundamental understanding of the propulsion system at the microscale in a magnetically driven manner, followed by a summary of diverse BMMs based on different microorganisms and body's own cells along with their relevant applications. Finally, the review discusses how BMMs contribute to the advancements of microrobots, the current challenges of using BMMs in practical clinical settings, and the future perspectives of this exciting field. STATEMENT OF SIGNIFICANCE: Biohybrid magnetic microrobots (BMMs), composed of biological entities and functional parts, hold great potential and serve as a novel and promising platform for biomedical applications such as targeted drug delivery. This review comprehensively summarizes the recent advancements in BMMs for biomedical applications, mainly focused on the representative propulsion modalities in a magnetically propelled manner and diverse designs of BMMs based on different biological entities, including microorganisms and body's own cells. We hope this review can provide ideas for the future design, development, and innovation of micro/nanorobots in the field of biomedicine.

A programmed surface on dental implants sequentially initiates bacteriostasis and osseointegration.

Osteogenesis surrounding dental implants is initiated by a series of early physiological events, including the inflammatory response. However, the persistence of an anti-infection surface often results in compromised histocompatibility and osseointegration. Here, we presented a programmed surface containing both silver nanoparticles (AgNPs) and silver ions (Ag+) with a heterogeneous structure and time-dependent functionalities. The AgNPs were located at the surface of the heparin-chitosan polyelectrolyte coating (PEM), whereas Ag+ was distributed at both the surface and inside of the coating under optimized conditions (pH=4). The optimized coating (Ag-4) exhibited potent bactericidal activity at the early stage (12 and 24 h after inoculation) and a sustained antibacterial efficacy in the subsequent stage (one or two weeks), as it gradually depleted. Furthermore, compared to coatings with sustained high silver concentrations in bacteria-cell coculture experiments, the degradable Ag-4 coating demonstrated improved cytocompatibility, better cell viability, and morphology over time. At a later stage (within one month), the in vivo test revealed that Ag-4-coated titanium had superior histocompatibility and osteogenesis outcomes compared to bare titanium in a bacteria-exposed environment. The programmed surface of dental implants presented in this study offers innovative ideas for sequential antibacterial effects and osseointegration.

Oribron: An Origami-Inspired Deformable Rigid Bronchoscope for Radial Support.

The structure of a traditional rigid bronchoscope includes proximal, distal, and body, representing an important means to treat hypoxic diseases. However, the body structure is too simple, resulting in the utilization rate of oxygen being usually low. In this work, we reported a deformable rigid bronchoscope (named Oribron) by adding a Waterbomb origami structure to the body. The Waterbomb's backbone is made of films, and the pneumatic actuators are placed inside it to achieve rapid deformation at low pressure. Experiments showed that Waterbomb has a unique deformation mechanism, which can transform from a small-diameter configuration (#1) to a large-diameter configuration (#2), showing excellent radial support capability. When Oribron entered or left the trachea, the Waterbomb remained in #1. When Oribron is working, the Waterbomb transforms from #1 to #2. Since #2 reduces the gap between the bronchoscope and the tracheal wall, it effectively slows down the rate of oxygen loss, thus promoting the absorption of oxygen by the patient. Therefore, we believe that this work will provide a new strategy for the integrated development of origami and medical devices.

Customizable single-layer hydrogel robot with programmable NIR-triggered responsiveness.

Hydrogel robots are widely used in biomedical fields due to their excellent biocompatibility and response to external stimuli. However, traditional processing methods cannot rapidly fabricate complex structures, and smart response strategies often rely on double-layer structures fabricated from two materials with significantly different swelling properties. In this study, we present a single-layer hydrogel robot that can be fabricated in one step using a high-precision digital light processing (H-P DLP) 3D printing system. The robot has structural differences and the ability to maintain a repetitive response. Additionally, we fabricated several robot grippers to demonstrate their potential for customization and programming, as well as their potential applications in cargo delivery. Our work provides a new approach to achieve the formation and response of various irregular hydrogels, which is expected to advance the development of biomedical applications.

Built-up sodium alginate/chlorhexidine multilayer coating on dental implants with initiating anti-infection and cyto-compatibility sequentially for soft-tissue sealing.

Soft-tissue sealing at transmucosal sites is very important for preventing the invasion of pathogens and maintaining the long-term stability and function of dental implants. However, the colonization of oral pathogens on the implant surface and surrounding soft tissues can disturb the early establishment of soft-tissue sealing and even induce peri-implant infection. The purpose of this study was to construct two antibacterial coatings with 5 or 10 sodium alginate/chlorhexidine bilayers on titanium surfaces using layer-by-layer self-assembly technology to promote soft-tissue sealing. The corresponding chemical composition, surface topography, wettability and release behaviour were investigated to prove that the resultant coating of sodium alginate and chlorhexidine was coated on the porous titanium surface. In-vitro and in-vivo antibacterial results showed that both prepared coatings inhibited or killed the bacteria on their surfaces and the surrounding areas to prevent plaque biofilm formation, especially the coating with 10 bilayers. Although both coatings inhibited the initial adhesion of fibroblasts, the cytocompatibility gradually improved with coating degradation. More importantly, both coatings achieved cell adhesion and proliferation in an in-vitro bacterial environment and effectively alleviated bacteria-induced subcutaneous inflammation in-vivo. Therefore, this study demonstrated that the multilayered coating could prevent implant-related infections in the initial stage of implant surgery and then improve soft-tissue integration with implant devices.

PIP2 Alteration Caused by Elastic Modulus and Tropism of Electrospun Scaffolds Facilitates Altered BMSCs Proliferation and Differentiation.

Aligned submicron fibers have played an essential role in inducing stem cell proliferation and differentiation. In this study, it is aimed to identify the differential causes of stem cell proliferation and differentiation between bone marrow mesenchymal stem cells (BMSCs) on aligned-random fibers with different elastic modulus, and to change the differential levels through a regulatory mechanism mediated by B-cell lymphoma 6 protein(BCL-6) and miRNA-126-5p(miR-126-5p). The results showed that phosphatidylinositol(4,5)bisphosphate alterations are found in the aligned fibers compared with the random fibers, which has a regular and oriented structure, excellent cytocompatibility, regular cytoskeleton, and high differentiation potential. The same trend is actual for the aligned fibers with a lower elastic modulus. The level of proliferative differentiation genes in cells is altered by BCL-6 and miR-126-5p mediated regulatory mechanisms to make the cell distribution nearly consistent with the cell state on low elastic modulus aligned fibers. This work demonstrates the reason for the difference of cells between the two kinds of fibers and on fibers with different elastic modulus. These findings provide more insights for understanding the gene-level regulation of cell growth in tissue engineering.

Dynamically reversible cooperation and interaction of multiple rotating micromotors.

Micromotors have been shown to have great potential in various fields (e.g., targeted therapeutics, self-organizing systems), and research on the cooperative and interactive behaviours of multiple micromotors could potentially revolutionize many fields in terms of performing multiple or complex tasks to compensate for the limitations of individual micromotors; however, dynamically reversible transitions among diverse behaviours remain much less explored, and such dynamic transformations are advantageous for achieving complex tasks. Here, we present a microsystem consisting of multiple disk-like micromotors capable of performing reversible transformations between cooperative and interactive behaviours at the liquid surface. The micromotors with aligned magnetic particles in our system have great magnet properties, which provides a strong magnetic interaction with each other and is vital for the whole microsystem. We offer and analyse the physical models among multiple micromotors concerning the cooperative and interactive modes in the lower and higher frequency ranges, respectively, between which the state transformation can reversibly occur. Furthermore, based on the proposed reversible microsystem, the feasibility of the application of self-organization is verified by demonstrating three different dynamic self-organizing behaviours. Our proposed dynamically reversible system has great potential to serve as a paradigm for studying cooperative and interactive behaviours among multiple micromotors in the future.

Interactive and synergistic behaviours of multiple heterogeneous microrobots.

Microrobots have been extensively studied for biomedical applications, and significant innovations and advances have been made in diverse aspects of the field. However, most studies have been based on individual microrobots with limited capabilities, constraining their scalability of functions for practical use. Here, we demonstrate the interactive and synergistic behaviours of multiple microrobots that are heterogeneous or incompletely homogeneous. A frequency-response theory is proposed where in a certain frequency range of an external rotating magnetic field (RMF), microrobots with dispersed and linearly aligned magnetic nanoparticles (MNPs) would exhibit similar and different behaviour, respectively. These microrobots rotate following the rotation of the external field, and such complete rotational motion is interrupted when the frequency exceeds a certain value, called the critical frequency (cf), but such behaviour is more prominent in microrobots with linear MNPs. Upon further investigating the effect of various parameters on the cf of the microrobots during the fabrication process, we find that heterogeneous microrobots with specific cf values can be customized. In addition, experiments and simulations are combined to show the hydrodynamic behaviours around the rotating microrobots at different frequencies. Based on these findings, the interactive and synergistic behaviours of multiple microrobots are presented, which suggests great potential for the independent execution of multiple tasks or the synergistic performance of complex tasks and is significant for the future development of interactive synergistic microrobots in the biomedical field.

Coaxial structured drug loaded dressing combined with induced stem cell differentiation for enhanced wound healing.

Controllable drug-loaded dressings combined with induced stem cell differentiation have received considerable interest. In this study, a directional core-shell drug-loaded magnetocaloric response PCL/Gelatin-Antibiotics/Fe3O4 multifunctional dressing was developed. Due to the magnetothermal heating effect of magnetic nanoparticles and the contraction of elastic electrospun fibers, the fibers release antibiotics as needed to prevent drug-resistant infection. IV collagenase catalyzes the degradation of gelatin by achieving an optimum reaction temperature, the purpose of which is also to reduce the viscosity of liquid gelatin and promote the release of drugs. With the sacrifice of gelatin, the directional structure of scaffold and the internal steric hindrance promoted stem cell differentiation and wound healing. The expression of Vimentin, VEGF, bFGF, TGF-ß, and THY1 was confirmed by fluorescence immunostaining and RT-PCR. Western blot was used to detect expression of Vimentin, collagen, CD34, and CD31 in the (5/5, v/v) PCL/gelatin scaffold incubated with mouse wound. Therefore, the functional fibers can significantly accelerate the healing process.

Three-Dimensional Silk Fibroin/Chitosan Based Microscaffold for Anticancer Drug Screening.

Traditional monolayer cell cultures often fail to accurately predict the anticancer activity of drug candidates, as they do not recapitulate the natural microenvironment. Recently, three-dimensional (3D) culture systems have been increasingly applied to cancer research and drug screening. Materials with good biocompatibility are crucial to create a 3D tumor microenvironment involved in such systems. In this study, natural silk fibroin (SF) and chitosan (CS) were selected as the raw materials to fabricate 3D microscaffolds; Besides, sodium tripolyphosphate (TPP), and 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDC) were used as cross-linking agents. The physicochemical properties of obtained scaffolds were characterized with kinds of testing methods, including emission scanning electron microscopy, x-ray photoelectron spectroscopy, fourier transform infrared spectroscopy, water absorption, and swelling ratio analysis. Cancer cell lines (LoVo and MDA-MB-231) were then seeded on scaffolds for biocompatibility examination and drug sensitivity tests. SEM results showed that EDC cross-linked scaffolds had smaller and more uniform pores with great interconnection than the TPP cross-linked scaffolds, and the EDC cross-linked scaffold exhibited a water absorption ratio around 1000% and a swelling ratio of about 72%. These spatial structures and physical properties could provide more adhesion sites and sufficient nutrients for cell growth. Moreover, both LoVo and MDA-MB-231 cells cultured on the EDC cross-linked scaffold exhibited good adhesion and spreading. CCK8 results showed that increased chemotherapeutic drug sensitivity was observed in 3D culture compared with 2D culture, particularly in the condition of low drug dose (<1  µ M). The proposed SF/CS microscaffold can provide a promising in vitro platform for the efficacy prediction and sensitivity screening of anticancer drugs.

A Novel EMG-Based Hand Gesture Recognition Framework Based on Multivariate Variational Mode Decomposition.

Surface electromyography (sEMG) is a kind of biological signal that records muscle activity noninvasively, which is of great significance in advanced human-computer interaction, prosthetic control, clinical therapy, and biomechanics. However, the number of hand gestures that can be recognized is limited and the recognition accuracy needs to be further improved. These factors lead to the fact that sEMG products are not widely used in practice. The main contributions of this paper are as follows. Firstly, considering the increasing number of gestures to be recognized and the complexity of gestures, an extensible two-stage machine learning lightweight framework was innovatively proposed for multi-gesture task recognition. Secondly, the multivariate variational mode decomposition (MVMD) is applied to extract the spatial-temporal features from the multiple channels to the EMG signals, and the separable convolutional neural network is used for modelling. In this work, the experimental results for 52 hand gestures recognition task show that the average accuracy on each stage is about 90%. The potential movement information is mainly contained in the low-frequency oscillator of the sEMG signal, and the model performs better with the low-frequency oscillation from the MVMD algorithm on the second stage classification than that of other decomposition methods.

[Biomedical applications of bionic untethered micro-nano robots].

Bionic untethered micro-nano robots, due to their advantages of small size, low weight, large thrust-to-weight ratio, strong wireless mobility, high flexibility and high sensitivity, have very important application values in the fields of biomedicine, such as disease diagnosis, minimally invasive surgery, targeted therapy, etc. This review article systematically introduced the manufacturing methods and motion control, and discussed the biomedical applications of bionic untethered micro-nano robots. Finally, the article discussed the possible challenges for bionic untethered micro-nano robots in the future. In summary, this review described bionic untethered micro-nano robots and their potential applications in biomedical fields.

Electrospun nanofibers promote wound healing: theories, techniques, and perspectives.

At present, the clinical strategies for treating chronic wounds are limited, especially when it comes to pain relief and rapid wound healing. Therefore, there is an urgent need to develop alternative treatment methods. This paper provides a systematic review on recent researches on how electrospun nanofiber scaffolds promote wound healing and how the electrospinning technology has been used for fabricating multi-dimensional, multi-pore and multi-functional nanofiber scaffolds that have greatly promoted the development of wound healing dressings. First, we provide a review on the four stages of wound healing, which is followed by a discussion on the evolvement of the electrospinning technology, what is involved in electrospinning devices, and factors affecting the electrospinning process. Finally, we present the possible mechanisms of electrospun nanofibers to promote wound healing, the classification of electrospun polymers, cell infiltration favoring fiber scaffolds, antibacterial fiber scaffolds, and future multi-functional scaffolds. Although nanofiber scaffolds have made great progress as a type of multi-functional biomaterial, major challenges still remain for commercializing them in a way that fully meets the needs of patients.

3D Printed Multi-Functional Hydrogel Microneedles Based on High-Precision Digital Light Processing.

Traditional injection and extraction devices often appear painful and cumbersome for patients. In recent years, polymer microneedles (MNs) have become a novel tool in the field of clinical medicine and health. However, the cost of building MNs into any shapes still remains a challenge. In this paper, we proposed hydrogel microneedles fabricated by high-precision digital light processing (H-P DLP) 3D printing system. Benefits from the sharp protuberance and micro-porous of the hydrogel microneedle, the microneedle performed multifunctional tasks such as drug delivery and detection with minimally invasion. Critical parameters for the fabrication process were analyzed, and the mechanical properties of MNs were measured to find a balance between precision and stiffness. Results shows that the stiffness and precision were significantly influenced by exposure time of each layer, and optimized printing parameters provided a balance between precision and stiffness. Bio-compatible MNs based on our H-P DLP system was able to execute drug injection and drug detection in our experiments. This work provided a low-cost and fast method to build MNs with 3D building, qualified the mechanical performance, drug injection, drug detection ability of MNs, and may be helpful for the potential clinical application.

Dynamic electro-regulation of the stiffness gradient hydrogels.

Hydrogels are promising biomaterials which provide bionic environments to study the effect of stiffness. A hydrogel with dynamically changeable stiffness can be used to further understand the dynamic biological processes such as embryonic development, tumorigenesis, etc. here we present an electro-regulation method which can dynamically control the stiffness of hydrogels with ionic crosslinks. By applying an electric field and controlling the voltage applied to the hydrogel the mechanical properties of the hydrogel can be changed. The voltage can directly change the stress-relaxation properties of the hydrogel, and after the voltage was applied for hundreds of seconds, a gradient stiffness was generated along the direction of the electric field. The value of gradient stiffness can be regulated by charge. With the increase of charge, the stiffness of the hydrogel near the anode increases, while the stiffness of the hydrogel near the cathode decreases. Experiments show that the electro-regulation method allows dynamic manipulation of the material properties of the hydrogel with ionic crosslinks. Dynamic electro-regulation of hydrogels is a powerful tool that will promote the study of the dynamic microenvironments and lead to a better understanding of the fundamental phenomena of the extracellular matrix.