The Application Progress of Nonthermal Plasma Technology in the Modification of Bone Implant Materials.

With the accelerating trend of global aging, bone damage caused by orthopedic diseases, such as osteoporosis and fractures, has become a shared international event. Traffic accidents, high-altitude falls, and other incidents are increasing daily, and the demand for bone implant treatment is also growing. Although extensive research has been conducted in the past decade to develop medical implants for bone regeneration and healing of body tissues, due to their low biocompatibility, weak bone integration ability, and high postoperative infection rates, pure titanium alloys, such as Ti-6A1-4V and Ti-6A1-7Nb, although widely used in clinical practice, have poor induction of phosphate deposition and wear resistance, and Ti-Zr alloy exhibits a lack of mechanical stability and processing complexity. In contrast, the Ti-Ni alloy exhibits toxicity and low thermal conductivity. Nonthermal plasma (NTP) has aroused widespread interest in synthesizing and modifying implanted materials. More and more researchers are using plasma to modify target catalysts such as changing the dispersion of active sites, adjusting electronic properties, enhancing metal carrier interactions, and changing their morphology. NTP provides an alternative option for catalysts in the modification processes of oxidation, reduction, etching, coating, and doping, especially for materials that cannot tolerate thermodynamic or thermosensitive reactions. This review will focus on applying NTP technology in bone implant material modification and analyze the overall performance of three common types of bone implant materials, including metals, ceramics, and polymers. The challenges faced by NTP material modification are also discussed.

3D printed multi-coupled bioinspired skin-electronic interfaces with enhanced adhesion for monitoring and treatment.

Skin-electronic interfaces have broad applications in fields such as diagnostics, therapy, health monitoring, and smart wearables. However, they face various challenges in practical use. For instance, in wet environments, the cohesion of the material may be compromised, and under dynamic conditions, maintaining conformal adhesion becomes difficult, leading to reduced sensitivity and fidelity of electrical signal transmission. The key scientific issue lies in forming a stable and tight mechanical-electronic coupling at the tissue-electronic interface. Here, inspired by octopus sucker structures and snail mucus, we propose a strategy for hydrogel skin-electronic interfaces based on multi-coupled bioinspired adhesion and introduce an ultrasound (US)-mediated interfacial toughness enhancement mechanism. Ultimately, using digital light processing micro-nano additive manufacturing technology (DLP 3D), we have developed a multifunctional, diagnostic-therapeutic integrated patch (PAMS). This patch exhibits moderate water swelling properties, a maximum deformation of up to 460%, high sensitivity (GF = 4.73), and tough and controllable bioadhesion (shear strength increased by 109.29%). Apart from outstanding mechanical and electronic properties, the patch also demonstrates good biocompatibility, anti-bacterial properties, photothermal properties, and resistance to freezing at -20 °C. Experimental results show that this skin-electronic interface can sensitively monitor temperature, motion, and electrocardiogram signals. Utilizing a rat frostbite model, we have demonstrated that this skin-electronic interface can effectively accelerate the wound healing process as a wound patch. This research offers a promising strategy for improving the performance of bioelectronic devices, sensor-based educational reforms and personalized diagnostics and therapeutics in the future. STATEMENT OF SIGNIFICANCE: Establishing stable and tight mechanical-electronic coupling at the tissue-electronic interface is essential for the diverse applications of bioelectronic devices. This study aims to develop a multifunctional, diagnostic-therapeutic integrated hydrogel skin-electronic interface patch with enhanced interfacial toughness. The patch is based on a multi-coupled bioinspired adhesive-enhanced mechanism, allowing for personalized 3D printing customization. It can be used as a high-performance diagnostic-therapeutic sensor and effectively promote frostbite wound healing. We anticipate that this research will provide new insights for constructing the next generation of multifunctional integrated high-performance bioelectronic interfaces.

Alginate/GelMA microparticles via oil-free interface shearing for untethered magnetic microbots.

Microrobots hold broad application prospects in the field of precision medicine, such as intravenous drug injection, tumor resection, opening blood vessels and imaging during abdominal surgery. However, the rapid and controllable preparation of biocompatible hydrogel microparticles still poses challenges. This study proposes the one-step direct acquisition of biocompatible sodium alginate and gelatin methacrylate (GelMA) hydrogel microparticles using an oil-free aqueous solution, ensuring production with a controllable generation frequency. An adaptive interface shearing platform is established to fabricate alginate/GelMA microparticles using a mixture of the hydrogel, photoinitiator, and Fe3O4 nanoparticles (NPs). By adjusting the static magnetic field intensity (Bs), vibration frequency, and flow rate (Q) of the dispersed phase, the size and morphology of the hydrogel microparticles can be controlled. These hydrogel microparticle robots exhibit magnetic responsiveness, demonstrating precise rotating and rolling movements under the influence of an externally rotating magnetic field (RMF). Moreover, hydrogel microparticle robots with a specific critical frequency (Cf) can be customized by adjusting the Bs and the concentration of Fe3O4 NPs. The directional in situ untethered motion of the hydrogel microparticle robots can be successfully realized and accurately controlled in the climbing over obstacles and in vitro experiments of animals, respectively. This versatile and fully biodegradable microrobot has the potential to precisely control movement to bone tissue and the natural cavity of the human body, as well as drug delivery.

Enhanced neural recovery and reduction of secondary damage in spinal cord injury through modulation of oxidative stress and neural response.

Spinal cord injury (SCI) presents a critical medical challenge, marked by substantial neural damage and persistent functional deficits. This study investigates the therapeutic potential of cold atmospheric plasma (CAP) for SCI, utilizing a tailored dielectric barrier discharge (DBD) device to conduct comprehensive in vivo and in vitro analyses. The findings show that CAP treatment significantly improves functional recovery after SCI, reduces neuronal apoptosis, lowers inflammation, and increases axonal regeneration. These findings illustrate the efficacy of CAP in fostering a conducive environment for recovery by modulating inflammatory responses, enhancing neuronal survival, and encouraging regenerative processes. The underlying mechanism involves CAP's reactive oxygen species (ROS) reduction, followed by activating antioxidant enzymes. These findings position CAP as a pioneering approach for spinal cord injury (SCI) treatment, presenting opportunities for improved neural recovery and establishing a new paradigm in SCI therapy.

Cold Air Plasma Inhibiting Tumor-Like Biological Behavior of Rheumatoid Arthritis Fibroblast-Like Synovial Cells via G2/M Cell Cycle Arrest.

Background: Rheumatoid arthritis fibroblast-like synovial cells (RA-FLS) have become the core effector cells for the progression of rheumatoid arthritis due to their "tumor-like cell" characteristics, such as being able to break free from growth restrictions caused by contact inhibition, promoting angiogenesis, invading surrounding tissues, and leading to uncontrolled synovial growth. In recent years, cold air plasma (CAP) has been widely recognized for its clear anticancer effect. Inspired by this, this study investigated the inhibitory effect of CAP on the tumor-like biological behavior of RA-FLS through in vitro experiments. Methods: Treatment of RA-FLS with CAP at different time doses (0s, 30s, 60s, 120s). 5-ethynyl-2'-deoxyuridine (EdU) proliferation assay was used to determine the cell viability. Analysis of cell migration and invasion was performed by wound-healing assay, transwell assay and immunofluorescent staining for f-actin, respectively. Flow cytometry technique was used for analysis of cell cycle and determination of reactive oxygen species (ROS). Hoechst staining was used for analysis of cell apoptosis. Protein expression was analyzed by Western blot analysis. Results: Molecular and cellular level mechanisms have revealed that CAP blocks RA-FLS in the G2/M phase by increasing intracellular reactive oxygen species (ROS), leading to increased apoptosis and significantly reduced migration and invasion ability of RA-FLS. Conclusion: Overall, CAP has significant anti proliferative, migratory, and invasive effects on RA-FLS. This study reveals a new targeted treatment strategy for RA.

Cold plasma turns mixed-dye-contaminated wastewater bio-safe.

The excessive and uncontrollable discharge of diverse organic pollutants into the environment has emerged as a significant concern, presenting a substantial risk to human health. Among the advanced oxidation processes used for the purification of wastewater, cold plasma technology is superior in fast and effective decontamination but often fails facing mixed pollutants. To address these issues, here we develop the new conceptual approach, plasma process, and proprietary reactor that ensure, for the first time, that the efficiency of treatment (114.7%) of two mixed organic dyes, methylene blue (MB) and methyl orange (MO), is higher than when the two dyes are treated separately. We further reveal the underlying mechanisms for the energy-efficient complete degradation of the mixed dyes. The contribution of plasma-induced ROS and the distinct degradation characteristics and mechanism of pollutants in mixed treatment are discussed. The electron transfer pathway revealed for the first time suggest that the mixed pollutants reduce the overall redox potentials and facilitate electron transfer during the plasma treatment, promoting synergistic degradation effects. The integrated frameworks including both direct and indirect mechanisms provide new insights into the high-efficiency mixed-contaminant treatment. The degradation products for mixed degradation are revealed based on the identification of intermediate species. The plasma-treated water is proven safe for living creatures in waterways and sustainable fishery applications, using in vivo zebrafish model bio-toxicity assay. Overall, these findings offer a feasible approach and new insights into the mechanisms for the development of highly-effective, energy-efficient technologies for wastewater treatment and reuse in agriculture, industry, and potentially in urban water networks.

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.

Cold atmospheric pressure plasma: A potential physical therapy for rheumatoid arthritis hyperplastic synovium.

The most significant pathological change in rheumatoid arthritis (RA) is synovial hyperplasia within the joint. The production of a series of degrading enzymes and oxidative stress caused by synovial hyperplasia lead to severe bone and cartilage damage in rheumatoid joints. The core effector cell in hyperplastic synovium is fibroblast-like synovium cells, which can invade cartilage, cause inflammation, destroy joints, and show tumor-like anti-apoptosis characteristics. This study focused on the effect of cold atmospheric pressure plasma on proliferative synovium, and the results showed that no synovial hyperplasia, angiogenesis, or inflammatory infiltration was observed after cold atmospheric pressure plasma (CAP) treatment. The molecular and cellular mechanisms also reveal the spontaneous reactive oxygen species (ROS) cascade inducing apoptosis in rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) cells. This study proposes a potential physical therapy method for treating proliferative synovium and also provides ideas for the application of CAP in other types of tumor diseases.

A Meaningful Attempt: Applying Dielectric Barrier Discharge Plasma to Induce Polarization of Macrophages.

Macrophage polarization plays an important role in many macrophage-related diseases. This study was designed to preliminarily explore the effects of dielectric barrier discharge (DBD) plasma on the polarization direction and cell activity of macrophages with different phenotypes (ie, M0, M1, and M2). The M1 macrophage marker inducible nitric oxide synthase (iNOS) and M2 macrophage marker cluster of differentiation 206 (CD206) were detected by western blot (WB). The effects of DBD plasma on macrophage viability were analyzed by using a cell counting kit-8 detection kit. M0, M1, and M2 macrophages exhibited a decrease in iNOS expression and an increase in CD206 expression after the DBD plasma intervention. Additionally, the decrease in macrophage viability remained non-significant after initiating the intervention. DBD plasma can promote the transformation of M0 and M1 macrophages to M2 macrophages, and can further enhance the expression of the M2 macrophage phenotype marker CD206. Our study not only demonstrates the potential therapeutic value of DBD plasma for macrophage-related diseases, but it also provides a new direction for research to improve the treatment of macrophage-related diseases. © 2023 Bioelectromagnetics Society.

Cold air plasma improving rheumatoid arthritis via mitochondrial apoptosis pathway.

Rheumatoid arthritis (RA) has plagued physicians and patients for years due to the lack of targeted treatment. In this study, inspired by the commonality between rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) and cancer cells, the therapeutic effects of cold air plasma (CAP) on RA are studied systematically and thoroughly. In/ex vivo results show that CAP with the proper dosage significantly relieves symptoms including synovial hyperplasia, inflammatory infiltration, and angiogenesis and eliminates the root cause by triggering the self-antioxidant capability of the surrounding tissue. The mechanism on the molecular and cellular level is also revealed that the spontaneous reactive oxygen species (ROS) cascade induces the mitochondrial apoptosis pathway on RA-FLS. This study reveals a new strategy for targeted treatment of RA and the mechanistic study provides the theoretical foundation for future development of plasma medicine.

Does music therapy affect the global cognitive function of patients with dementia? A meta-analysis.

BACKGROUND: Studies have shown that music therapy can improve a variety of symptoms of patients with dementia. The impact of music therapy on the global cognition of patients with dementia is controversial now. OBJECTIVE: To explore whether music therapy has an effect on the global cognitive function of patients with dementia. METHODS: PubMed, Web of Science, Embase, Google Academy and National Knowledge Infrastructure were systematically searched to collect all literature studies published since the establishment of the database until November 2020. All randomized controlled trials that met the criteria of music therapy in the intervention group and standard care in the control group with outcome measures of Mini-mental State Examination (MMSE) were included. Analysis was performed using Stata 16.0. RESULTS: The results showed that compared with the control group, the MMSE score in the music therapy group was generally higher (MD = 0.86, 95% CI: 0.07-1.66, P = 0.03). CONCLUSIONS: The result of this study differs from those of previous relevant meta-analyses, suggesting that music therapy is likely to improve the global cognitive function of patients with dementia, but more rigorous clinical trials are still needed to provide more sufficient and real evidence.

A Wearable Augmented Reality Navigation System for Surgical Telementoring Based on Microsoft HoloLens.

This paper reports a new type of augmented reality (AR) system that integrates a Microsoft HoloLens device with a three-dimensional (3D) point tracking module for medical training and telementored surgery. In this system, a stereo camera is used to track the 3D position of a scalpel and transfer its coordinates wirelessly to a HoloLens device. In the scenario of surgical training, a virtual surgical scene with pre-recorded surgical annotations is superimposed with the actual surgical scene so that the surgical trainee is able to operate following virtual instructions. In the scenario of telementored surgery, the virtual surgical scene is co-registered with the actual surgical scene so that the virtual scalpel remotely mentored by an experienced surgeon provides the AR guidance for the inexperienced on-site operator. The performance characteristics of the proposed AR telementoring system are verified by benchtop experiments. The clinical applicability of the proposed system in telementored skin grafting surgery and fasciotomy is validated in a New Zealand rabbit model. Our benchtop and in vivo experiments demonstrate the potential to improve surgical performance and reduce healthcare disparities in remote areas with limited resources.