Bone tissue engineering (BTE) is pivotal for addressing bone defects. It integrates biomaterials, cells, and bioactive factors to mimic the natural bone microenvironment, thereby promoting bone regeneration and repair. In this system, scaffolds provide physical support and nutrient transport for cells. Three-dimensional (3D) printing revolutionizes BTE by fabricating customized scaffolds tailored to individual patients. As the cornerstone of 3D bioprinting, bioinks must meet strict biocompatibility and printability requirements to drive BTE advancement. In this review, we first explore the principles, advantages, and limitations of various bioprinting techniques. Furthermore, we also summarized recent breakthroughs and merits of three key photo-crosslinking reactions, including photoinitiated free radical crosslinking, photoclick crosslinking, and photo-conjugation crosslinking. Moreover, this review focused on the properties of natural polymers, synthetic polymers, and calcium phosphate-based inorganic materials in bioink formulation, as well as their BTE applications. Finally, a concise outlook on the future advancement of photocurable bioinks was provided.

Pathological calcification is typically regarded as a pathological endpoint, representing the abnormal deposition of calcium salts in tissues. With the continuous advancement of research, scientists have explored novel therapeutic strategies involving the induced calcification of tumor cells, demonstrating its potential therapeutic capabilities. Recently, a pioneering study on the use of induced calcification to treat bacterial infections has been reported. This commentary first introduces the classification, etiology, and treatment of pathological calcification. Then, the antibacterial effects of induced calcification therapy through the delicately designed antibacterial agent against methicillin-resistant Staphylococcus aureus (MRSA) are generally demonstrated and discussed. The underlying mechanism of induced calcification for the treatment of chronic lung infections and chronic osteomyelitis caused by MRSA is revealed from the perspectives of bacterial energy metabolism and immune modulation. At the end of this commentary, challenges and future directions for induced calcification therapy are also briefly presented.

Osteoarthritis (OA) is a common degenerative joint disease driven by synovial inflammation and immune dysregulation, especially in the knee joint. Macrophages play a key role in innate immunity and can differentiate into pro-inflammatory M1 or anti-inflammatory M2 phenotypes, which have a significant impact on the progression of OA. Electrospun nanofiber membranes, as a promising biomaterial, can regulate the polarization of macrophages towards the M2 phenotype, thereby reducing inflammation and promoting tissue repair. This article systematically reviews the immune microenvironment of OA, the mechanism of macrophage polarization, and the role of nanofiber membranes in the treatment of OA. In conclusion, the continuous development of nanofiber membrane technology will greatly change the future of OA treatment and provide more effective and efficient solutions for patients.

Bacterial infections caused by biomaterials represent a significant challenge in the clinical management of implants. Implant infections not only lead to surgical failure, prolong patient hospital stays, and increase healthcare costs, but may also trigger severe complications and even pose a threat to the patient’s life. Research on antimicrobial materials for metal implant surfaces holds significant importance. By developing antimicrobial coatings for implant surfaces or utilizing inherently antimicrobial metallic materials, bacterial adhesion and growth on implant surfaces can be effectively suppressed, thereby reducing infection rates and improving the success rate of implant surgeries. Simultaneously, the development of antimicrobial materials also contributes to advancing medical materials science, offering new approaches and methodologies for antimicrobial design in other medical devices. This holds broad application prospects and significant socioeconomic benefits.

Peripheral nerve injury remains a significant clinical challenge, particularly in cases of long-gap defects. While autologous nerve grafting serves as the current gold standard treatment, its limitations include donor site morbidity and limited donor nerve availability. As a promising alternative, nerve guidance conduits (NGCs) have emerged within the field of tissue engineering. Incorporating electrical stimulation into NGCs has been shown to facilitate peripheral nerve repair by promoting Schwann cell migration and neurite extension. A significant advancement in this area is the application of piezoelectric biomaterials, which generate endogenous electrical signals from physiological mechanical stimuli. This self-powered mechanism eliminates the need for external power sources or additional surgical interventions. This review systematically examines the material design, fabrication strategies, and electromechanical properties of piezoelectric NGCs, along with their recent applications for enhancing Schwann cell function, guiding axonal growth, and promoting functional nerve recovery. Furthermore, it discusses current challenges and future directions, aiming to provide novel insights for the development of next-generation intelligent neural repair materials.

Adrenaline hydrochloride is an indispensable drug in clinical emergencies, effective at alleviating critical conditions such as weak pulse and respiratory distress. However, the catechol moiety in its molecular structure is prone to oxidation, leading to drug degradation, reduced efficacy, and a short half-life. These inherent limitations significantly restrict its broader clinical application. To address this challenge, this study constructed an intelligent microneedle patch designed to stabilize drugs. We first grafted 3-aminophenylboronic acid onto silk fibroin via 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide/N-hydroxysuccinimide coupling chemistry. This design enables the formation of reversible boronic ester bonds between phenylboronic acid and the catechol structure of adrenaline, effectively shielding the oxidation-sensitive sites and significantly enhancing the drug’s storage stability. Upon insertion into the skin, the microneedles encounter the physiological environment where glucose competitively binds to the phenylboronic acid, triggering the cleavage of the boronic ester bonds and resulting in the on-demand release of adrenaline. A cumulative drug release rate of approximately 60% was achieved over 24 hours. This study proposes a novel “protection-release” dual-functional design, offering a new strategy for the efficient delivery and stabilized storage of catechol-containing drugs. This approach holds significant promise for applications in emergency medicine and the long-term storage of pharmaceuticals.

The effectiveness of hemostasis during spinal surgery directly influences the surgical success rate and patient prognosis. Minimally invasive surgery has multiple advantages, including reductions in intraoperative and postoperative blood loss, minimized damage to surrounding tissues, and alleviation of postoperative pain. However, when the spinal epidural venous plexus is located within deep cavities, achieving sufficient hemostasis often presents challenges due to limited operating space and the limitations of traditional hemostatic materials. In recent years, novel adhesive hemostatic hydrogels have served as local injectable hemostatic agents. These hydrogels function through dual mechanisms: physical blockage of bleeding sites and biological activation, such as promoting coagulation cascades, thereby showing significant advantages in bleeding control at complex anatomical sites. Accordingly, this article systematically reviews the progress of basic research and clinical translation related to hemostatic materials over the past five years to provide a scientific foundation for optimizing perioperative hemostatic strategies.

Immunotherapy has emerged as a transformative approach in cancer therapeutics, yet its clinical translation remains constrained by significant challenges, including tumor immune evasion mechanisms and suboptimal efficacy of monotherapy, collectively impeding the full realization of its therapeutic potential. With their unique physicochemical properties, tunable enzyme-mimetic activities, and ability to induce cuproptosis, copper-based nanomaterials provide a new solution to overcome these limitations and have become a research focus in the field of targeted antitumor immunotherapy. This review systematically summarizes the research progress of copper-based nanomaterials in tumor immunotherapy, with a focus on discussing their core antitumor immunological mechanisms. These materials trigger immunogenic cell death by inducing cuproptosis and activate the body’s innate and adaptive immune responses through the release of damage-associated molecular patterns, such as calreticulin, high-mobility group box 1, adenosine triphosphate, and mitochondrial DNA. Meanwhile, they remodel the immunosuppressive tumor microenvironment by alleviating tumor hypoxia, scavenging immunosuppressive metabolites, and reducing immunosuppressive cells. On this basis, this review further analyzes the combined therapeutic strategies of copper-based nanomaterials with immune checkpoint blockade, photodynamic therapy, photothermal therapy, sonodynamic therapy, chemotherapy, and radiotherapy. It also elaborates on the specific mechanisms by which various combined regimens enhance antitumor efficacy, such as through synergistically amplifying oxidative stress, strengthening cell death effects, or improving therapeutic targeting. Additionally, this review discusses the current challenges faced by copper-based nanomaterials in clinical translation and points out future development directions. This review aims to provide a theoretical basis and practical guidance for the clinical translation of multifunctional copper-based nanoplatforms. It also offers new insights for the development of tumor immunotherapies based on metal and redox biology, helping to overcome immune tolerance and improve the efficacy of antitumor treatment.

Lipid nanoparticle-based messenger RNA (mRNA) delivery system have ushered in a new era of gene therapeutics. However, their clinical advances have been impeded by the inherent liver tropism of lipid nanoparticles (LNPs), which limits extrahepatic applications. Herein, we highlight two recent studies written in Nature Materials. Guided by surface interface molecular mechanics, Chang and his colleagues worked on the intelligent design of targeted peptides combined with lipids. Concurrently, Lin and his colleagues explored novel organ-specific peptide-lipid materials and analyzed important LNP traits that co-determined the in vitro/in vivo transfection discrepancy. The resulting peptide-modified lipids exhibit the capacity for targeted delivery to various organs and realize gene editing function. These studies jointly established a modular platform that provides a rational and predictable strategy for designing tissue-specific LNPs, thereby paving the way for next-generation mRNA-based therapeutics.

This review examines recent advances and applications of three-dimensional (3D) printing technology in orthopedic fracture management, with a particular focus on its transformative role in personalized treatment strategies. The introduction of patient-specific 3D-printed implants and fracture plates has markedly improved surgical outcomes by reducing operative time, enhancing anatomical alignment, and promoting bone healing. By enabling the fabrication of customized implants, 3D printing provides an innovative approach for managing complex fractures and bone defects, particularly in cases where conventional methods are inadequate. Key benefits discussed include the development of tailored fracture plates, bone scaffolds, and bioactive materials that support bone regeneration. The review also explores the potential of emerging technologies such as four-dimensional printing and bioprinting, which allow for the creation of dynamic implants capable of adapting to biological changes and facilitating tissue regeneration. In addition, the integration of artificial intelligence into preoperative planning and implant design is highlighted for its contribution to improving surgical precision and individualized treatment. This review consolidates the latest advancements while also addressing challenges, including high production costs and regulatory barriers, that must be overcome for widespread clinical adoption. In conclusion, the future of orthopedic fracture management is expected to be significantly reshaped by the continuous evolution of 3D printing technologies, offering more personalized, effective, and efficient solutions for patients. As these innovations progress, 3D printing is anticipated to play a pivotal role in advancing orthopedic surgery and ultimately improving patient outcomes.

As the primary skin-contact interface in wearable electrocardiograph (ECG) devices, epidermal electrodes play a pivotal role in determining both signal quality and biocompatibility. With continuous advancements in materials science and structural engineering, next-generation flexible and stretchable bioelectrodes have emerged, enabling long-term ECG monitoring and offering superior signal-to-noise ratios compared to conventional clinical electrodes. Their performance in ensuring reliable signal acquisition and user comfort is primarily governed by key interfacial mechanical and electrical properties, including mechanical compliance (i.e., flexibility and stretchability), interfacial adhesion (i.e., conformability and adhesion strength), and electrical characteristics (i.e., contact impedance). In recent years, significant progress has been made in enhancing the signal acquisition capabilities of flexible and stretchable bioelectrodes by optimizing these critical interfacial attributes. This review highlights the latest advances in conformable epidermal electrodes, encompassing traditional wet electrodes, flexible dry electrodes, novel dry electrodes based on organic electrochemical transistors, and integrated wearable systems. We systematically examine strategies for improving skin-electrode interface performance in ECG monitoring. Finally, we discuss ongoing challenges and future directions to advance epidermal electrode technologies for next-generation wearable healthcare applications.

Diabetic foot ulcers (DFUs) are a serious complication of diabetes and often result in amputation. Traditional wound care methods have limitations in addressing the complex pathophysiology of DFUs. Hydrogel dressings, a type of biomaterial, have emerged as promising candidates for treating DFUs due to their biocompatibility, ability to retain moisture, and potential to incorporate therapeutic agents. Hydrogels create a moist environment, promote cell migration, and reduce inflammation, thereby supporting wound healing. Incorporating bioactive molecules, such as growth factors and anti-inflammatory agents, can further enhance the effectiveness of hydrogels. Additionally, stem cells can be loaded into hydrogels to improve tissue regeneration and help modulate the wound microenvironment. Recent advancements in hydrogel technology have also led to the development of smart hydrogels that can respond to changes in wound conditions, such as glucose levels and pH. These intelligent dressings offer personalized care by delivering targeted treatments based on real-time wound data. This review explores the mechanisms behind DFU development, the role of hydrogels in wound healing, and recent progress in hydrogel technologies for personalized DFU care.

Bone defects represent a significant orthopedic challenge, with associated disorders continue to pose clinical difficulties. In the biomedical field, advancements in three-dimensional (3D) printing technology have established bone tissue engineering (BTE) scaffolds as a promising approach for effective treatment. These scaffolds not only provide structural support for cells but also serve as templates to guide bone tissue regeneration. In recent years, owing to their exceptional physicochemical properties, two-dimensional nanomaterials (2D NMs) have garnered increasing attention and have been widely explored as additives in the fabrication of BTE scaffolds. This review centers on the most recent developments in the combination of 2D NMs and 3D printing for BTE applications. It begins with a concise summary of the common synthesis and surface modification methods of 2D NMs. Then, it offers a comprehensive overview of recent advancements in their use within BTE. Finally, it discusses current challenges and future perspectives regarding the application of 2D NMs-based 3D-printed scaffolds in bone tissue regeneration.

With the development of 3D printing technologies, cellulose has been explored to realize its sophisticated geometry fabrication in this field for a variety of applications. This review focuses specifically on the latest research progress of 3D printing cellulose by discussing the characteristics of cellulose materials, different 3D printing technologies, and their optimal performance for applications in various fields like biomedicine, food packaging, and tissue engineering. The challenges of preparing 3D printing “ink” of cellulose using dissolved cellulose or nanocellulose are introduced. Finally, the corresponding applications of cellulose using 3D printing are classified and the strategies to optimize production performance are provided.

This mini-review explores advancements in the synthesis of nano-carrier-based drug delivery systems (NDDS) using microfluidic chip technology and their evaluation using tumor organ-on-a-chip models. We discuss the principles and advantages of hydrodynamic fluid focusing and micromixer for synthesizing polymeric nano-carriers, highlighting their ability to precisely control particle size, shape, and surface properties. The functionalization of nano-carriers for targeted drug delivery is also explored, emphasizing the potential for personalized medicine. The review emphasizes the use of tumor organ-on-a-chip models for evaluating NDDS, highlighting their ability to simulate physiological environments and provide dynamic and controllable evaluation platforms. This approach holds great promise for enhancing our understanding of drug behaviors and accelerating the translation of nanomedicines from bench to bedside.

Brain diseases, including psychosis, neurological disorders, strokes, etc., account for more than 15% of all global health damage, which is higher than that caused by cancer and cardiovascular diseases. Brain health and the treatment of brain diseases have become major challenges of the 21st century. The past few decades have witnessed a series of significant advances in human brain science research. The pathogenesis of brain diseases at the molecular and genetic level is being revealed, indicating promising outcomes. However, the existence of the blood-brain barrier (BBB) significantly impedes the delivery of drugs and genes to the brain, which seriously hinders the treatment of brain diseases. This review article provides a brief overview of the concept and history of the BBB. We focus on the critical obstacles and solutions of different kinds of therapeutics, including small molecule drugs, peptides, proteins, and genes, to break through the BBB. Delivery mechanisms, strategies, and vehicles are summarized. Recent advances and efforts in drug delivery studies that aim to overcome the BBB will greatly facilitate the development of brain disease treatment.

Nanoscience and nanotechnology have steered in the new era of medical innovation and offered a promising solution to the longstanding challenges in the healthcare due to size dependent physicochemical properties. The ability to engineer the specific nanostructures makes the nanomaterials more attractive and find potential applications in the field of biomedical sciences. Among various noble metal nanomaterials, copper and copper-based nanomaterials are considered as a unique nanomaterial for multitude of the biomedical applications. Plant biomolecules contain various terpenoids, alkaloids, flavonoids, flavones, proteins, polyphenols, saponins, tannins, steroids, as well as other nutritional compounds; which are capable of acting as reducing and capping agents for copper-based nanomaterials formation. Biosynthesis of copper-based nanomaterials has great advantages due to less-toxicity, biocompatible, antiviral or anti-bacterial properties for the development of bio-sensor or drug delivery application. In this mini-review, the biosensor and drug delivery potential of the copper-based functional nano-formulation are discussed.

A large amount of medical equipment is now extensively utilized in healthcare institutions to assist clinical practitioners in the diagnosis and treatment of diseases. And the applications of such advanced and sophisticated medical equipment have greatly improved the quality of patient care, significantly alleviated the sufferings of patients, and facilitated their rehabilitation. Nevertheless, failures and malfunctions of medical equipment have compromised its reliability and effectiveness as well as jeopardizing the safety of patients and clinical staffs. And a majority of the failures can be attributed to the insufficient and inappropriate maintenance. Therefore, it is imperative to implement effective maintenance management to ensure that medical equipment is in its optimal function, and thereby mitigating the clinical risk resulted by adverse events. The presented review mainly discussed the maintenance strategies of medical equipment including corrective maintenance, preventive maintenance and predictive maintenance. In order to replace the fixed-interval of preventive maintenance, we systematically discussed methods to adjust the maintenance period. Additionally, two strategies to predicting future failures of medical equipment through processing and analyzing the maintenance data obtained from the historical maintenance logs and condition data collected by the embedded sensors are elaborated. Besides, the classification and life cycle of medical equipment are also summarized.

Due to imaging sensors’ constraints, it is difficult to acquire a medical image that subsequently incorporates functional metabolic data and anatomical tissue characteristics. An important tool to aid in diagnostic procedures and intra-operative management is multimodal medical image fusion, an efficient method to combine the supplemental information gathered from numerous modalities. This research proposes a unique fusion approach for multimodal medical images that makes use of mean filter and maximum symmetric surround saliency detection. First, the images to be fused are decomposed into base layer and a series of detail layers via mean filter. While the guided filtering based fusion rule is used to merge the detail layers, for the fusion of base layer, a linear summation is employed. The fused base and detail images are subsequently combined to construct the final fused image. The proposed medical image fusion method performed more effectively than existing cutting-edge approaches in the context of both visual appearance and quantitative assessment, according to careful evaluation on a widely used database. The proposed method overcomes the challenge of cutting-edge image fusion methods in maintaining substantial edges and energy information on multi-modal medical images.

Peptic ulcer is a common disease with a high clinical incidence and frequent recurrences. The well-characterized galactomannan-type polysaccharide, extracted from Cassia grandis seeds, can accelerate the stages of wound healing and improve the remodeling of the extracellular matrix of injured tissues; this way, the gastroprotective potential of the galactomannan was proposed to be evaluated in the treatment of rat peptic ulcers induced by ethanol. Galactomannan was extracted by ethanol precipitation and prepared at 0.1, 1.0, and 10 mg/kg concentrations. Male Wistar rats were randomly divided into groups (n = 5) and orally treated with saline (negative control, NC), galactomannan at 0.1 mg/kg (G0.1), galactomannan at 1.0 mg/kg (G1), galactomannan at 10 mg/kg (G10), and lansoprazole 30 mg/kg (positive control, CP). Ethanol (1 mL/100 g of body mass) was administered 1 h after the treatments and, after another hour, the animals were euthanized. The stomachs were removed, fixed between Petri dishes, and photographed to calculate the percentage of the injured regions by computerized software. Histological analysis and the quantification of lipid peroxidation and reduced glutathione (GSH) were also performed. G1 and G10 reduced the injured area (P < 0.001) by 40 and 36%, respectively, concerning NC. It was observed the preservation of the gastric mucosa in all of the animals treated with galactomannan, in addition to reduced (P < 0.001) lipid peroxidation and GSH levels higher (P < 0.05) than NC. The galactomannan extracted from C. grandis seeds showed gastroprotective activity at 1.0 and 10 mg/kg by reducing the area of ulceration and oxidative stress.

The spike protein of SARS-CoV-2 plays an important role in binding, fusion, and host entry. In this study, we have predicted interatomic bond strength between receptor binding domain (RBD) and angiotensin converting enzyme-2 (ACE2) using machine learning (ML), that matches with expensive ab initio calculation result. We collected bond order result from ab initio calculations. We selected a total of 18 variables such as bond type, bond length, elements and their coordinates, and others, to train ML models. We then trained five well-known regression models, namely, Decision Tree regression, KNN Regression, XGBoost, Lasso Regression, and Ridge Regression. We tested these models on two different datasets, namely, Wild type (WT) and Omicron variant (OV). In the first setting, we used 90% of each dataset for training and 10% for testing to predict the bond order. XGBoost model outperformed all the other models in the prediction of the WT dataset. It achieved an R2 Score of 0.997. XGBoost also outperformed all the other models with an R2 score of 0.9998 in the prediction of the OV dataset. In the second setting, we trained all the models on the WT (or OV) dataset and predicted the bond order on the OV (or WT) dataset. Interestingly, Decision Tree outperformed all the other models in both cases. It achieved an R2 score of 0.997.

Biodegradable pH-responsive hydrogels have become a powerful tool in medicine for synthesizing wound dressings and drug delivery applications. The current study focuses on the development of crosslinked semi-interpenetrating polymer networks of chitosan/poly(ethylene glycol)/3-glycidyloxypropyltrimethoxy silane (GPTMS) blends containing honey and aloe vera gel. All hydrogels were prepared by physical blending and solution casting methods. Fourier transform infrared (FTIR) spectroscopy was performed to analyse the developed interactions among the polymers and crosslinker. To check the thermal behaviour and crosslinking density of all hydrogel matrixes, thermogravimetric analysis (TGA) was done. The effects of the crosslinker concentration on the swelling trend of all hydrogels were investigated against distilled water and buffers of varying pH. The hydrogel was found thermally stable with enhanced swelling rate, good moisture capability, and pH responsiveness. These properties and the material's cost-effectiveness suggest that the fabricated blend hydrogels can be suitable for wound dressing and other biomedical applications.

The demand for advanced cosmetics needed for remodeling to enhance beauty and fashion is on the increase in modern times. Also, some of the major parts of the human head that bring about great discomfort in the human body if not put in proper conditions are the teeth, nose, ears, and eyes. Among these parts, the teeth are highly susceptible to serious attack and damage at various stages of life. To date, pleasurable feeding would be practically impossible for humans without the aid of teeth that are responsible for cutting and chewing. However, as with other parts of the human body, there are always issues affecting the maxillofacial prosthesis and teeth, which are usually the result of aging, accidents, or diseases. These issues influence the rising need for the replacement of maxillofacial and dental bones with different materials that are developed to meet the structural and biocompatibility needs. Facial and dental implantations have brought about many modifications to human appearance in recent times. The implants are expected to be safe and acceptable to the body system as the patient grows since growth is crucial to human existence. As, growth is a function of the age group in human beings and, the three major age groups respond to growth at different rates. Thus, this review considers the influence of the human age group on maxillofacial and dental implants. The review provides an insight to the demand from each age group and the necessary guides on the selection of appropriate biomaterials as well as future expectations for maxillofacial and dental bones. This is essential because adequate knowledge of the age group of the patients who need maxillofacial and dental bones demands accurate prescriptions.

The success of dental operations with the use of implants mostly depends on the properties of the implant materials and their compatibility with the tissues of the human body. A number of physical compatibility criteria are known, which include biological stability, biocorrosion resistance, chemical stability, antimicrobial resistance, so an in-depth study of these criteria is relevant. Among the used implants, dielectric materials of natural and synthetic origin make up a large share. The peculiarity of such materials, in contrast to metal ones, is the ability to form, at a human body temperature of 310K, low-intensity electromagnetic radiation (EMR) of the microwave range, which interacts with the biotissue adjacent to the implant. Such EMR exerts an influence at the cellular level too. This effect of EMRin fact has not been investigated. The article discusses the physical basis of the formation of positive ("+") and negative ("-") microwave radiation flows that occur between the implant and the adjacent biotissue. By using a highly sensitive radiometric system, an experimental study of the radiation properties of the most used implant materials contacting with human body tissues was carried out. In the course of the research the levels of inherent radiation of a number of dental materials were determined, the calculation and evaluation of the coefficients of their radiation capacity was carried out. Comparing the radiation capacity of contacting dental materials with the level of radiation of the human body tissues made it possible to determine the level of their electromagnetic compatibility. Recommendations for the selection of the most used contacting dental materials based on the criterion of electromagnetic compatibility have been developed.

Facial palsy, or weakness of the facial muscles, arises from injury to the facial nerve and can lead to debilitating morbidity by affecting facial expression, speech, and daily activities. Playing a wind instrument, such as the saxophone, requires formation of an airtight seal with the instrument's mouthpiece through a coordinated effort of facial muscles known as embouchure. Consequently, facial palsy can impair a musician's ability to play a wind instrument. To address this functional disability, we present a novel three dimensional (3D) printed embouchure-assistive device designed for application in saxophone players with facial palsy. Quantitative and qualitative metrics were recorded, demonstrating improved duration of note sustain, increased mean air pressure within the mouthpiece during play, and subjectively improved patient comfort and overall tone quality with use of the device. We also include design iterations of the prototype device as they may serve as a template for broader applications in musicians with facial palsy.

Integration of inorganic fillers with polymer matrices opens up exciting possibilities for creating high-performance functional materials. Metal/metal oxides/silsesquioxanes as nanofillers are gaining attention for enhancing polymer matrices. Understanding the dispersion and interaction of these nanofillers is crucial for modifying properties in technological applications. Homogeneously dispersed fillers boost physiochemical and biological properties, like mechanical strength and biocompatibility. These functional materials are employed in tissue engineering and other healthcare applications, maintaining their characteristics even in challenging conditions. In the biomedical field, these fillers show promise in developing stimuli-responsive systems, drug delivery, gene vectors, and biological imaging.

In the last few years, a renewed interest has been devoted to the origin of life. Nucleic acids have a central role in biogenesis and prebiotic synthesis of ribose, purines and pyrimidines has been described. Particularly attractive is the idea that life on Earth was first founded on simple and autocatalytic RNA molecules (RNA world). RNA duplexes are formed by helical and antiparallel chains, but the rationale for these features is not yet known. An inverted (antiparallel) stacking of purine rings from guanosine and other nucleosides has been found in crystallographic studies. Molecular modeling also supports an inverted conformation, and this preferential stacking occurs when they are aggregated within a clay (montmorillonite) matrix, which is confirmed by spectral studies. Thus, crystallography, spectroscopy and molecular modeling allow proposing a "zipper" model in which antiparallel nucleosides stack within the clay matrix, and then high-energy polyphosphates form auto-intercalated single RNA chains. Unstacking and strand separation result in the shortening and inclination of the ribose-phosphate chains, leading to helicity, antiparallelism and base pairing by H-bonding, with formation of typical RNA structures such as hairpins, cloverleaves, hammerheads, dumbbells, circular viroids and virusoids. A "tetris" model for the prebiotic self-replication mechanism of these simple RNA duplexes, involving the formation of an RNA tetraplex, is also proposed.