The incidence of temporomandibular joint (TMJ) degeneration has been steadily increasing, with overloading identified as a major risk factor. This condition often leads to condylar cartilage degeneration, significantly affecting patients' quality of life; however, the molecular mechanisms underlying this process remain poorly understood, and effective treatments are still lacking. We utilized single-nucleus RNA sequencing to analyze the condylar cartilage in an overloading mouse model. This approach enabled the identification of 11 distinct cell types within the condylar chondrocytes. Through the application of pseudotime trajectory Analysis and cellchat analyses, we identified the key gene Acvr1b and its associated signaling pathway, which are crucial for regulating the terminal differentiation of condylar chondrocytes. This study utilized single-nucleus RNA sequencing and in vitro validation to investigate the role of Acvr1b in TMJ cartilage degeneration under overloading stress. Our findings reveal key pathways involved in chondrocyte differentiation, providing a theoretical basis for the development of targeted therapeutic interventions.
Artificial nerve conduits hold significant promise for treating nerve injuries, with researchers focusing on simplifying techniques to harness microstructures and functions to improve their therapeutic outcomes. Here, a type of conductive nerve guidance conduit (NGC) with orientated topological structures from ice-templating technology is presented for promoting peripheral nerve regeneration. Based on a temperature gradient generated by a thermoelectric cooling platform, conductive carbon nanotubes (CNTs) and methacrylated gelatin are introduced into the ice crystal template to create conductive conduits with unique oriented structures. Ascribed to such structures, together with the great conductivity of CNTs and the loaded nerve growth factors, the obtained conduits can direct the neurite extension and facilitate the differentiation and growth of nerve cells. By constructing rat models with long-segment sciatic nerve defects, it was confirmed that such conductive NGCs can effectively improve injured nerve regeneration and motor function recovery. These features reveal the practical application value and broad prospect of our prepared NGCs in improving peripheral nerve regeneration.
Pharmacological chemotherapy remains a cornerstone in treating osteosarcoma (OS), where the application of drug combinations not only enhances therapeutic efficacy but also mitigates adverse side effects. However, the absence of an efficient and reliable drug screening platform poses a significant challenge in optimizing these combination therapies. In this study, we introduce a novel OS chip designed to facilitate the high-throughput and precise evaluation of drug combination efficacy, addressing this critical gap in OS treatment research. Leveraging the precise control of microfluidic electrospray technology, we successfully fabricated core–shell microcarriers (CSMs) encapsulating OS cells with uniform size and monodisperse distribution. Through three-dimensional culture, OS cell spheroids were efficiently formed within the CSMs, which were subsequently integrated into a microfluidic chip equipped with a concentration gradient generator and cell culture chambers. This innovative platform enables high-throughput screening of single drugs and diverse drug combinations. Our results demonstrate that this OS-on-a-chip exhibits significant potential for clinical drug screening, offering a robust tool for optimizing therapeutic strategies in OS treatment.
Wounds represent a global and challenging healthcare issue, resulting in a cascade of consequences. Despite the widespread application of existing wound dressings, their performance and efficacy are significantly limited in terms of biocompatible matrices and functionalization for promoting vascularization and antimicrobial activity. In this study, we propose a drug-loaded microneedle based on a copolymer hydrogel composed of methacrylated chitosan and polyethylene glycol diacrylate incorporating antimicrobial peptide and vascular endothelial growth factor. These microneedles were applied to wounds where their degradation facilitated the release of the loaded drugs to exert antibacterial and angiogenic effects. In vitro experiments demonstrated that our microneedles exhibit uniform morphology, good structural integrity, controlled drug release, and other excellent properties. Upon interaction with cells and bacteria, they displayed biocompatibility and superior dual antibacterial capabilities. In an in vivo infectious wound model, the microneedles significantly promoted wound healing through their antibacterial and angiogenic effects, showing clear advantages over the control group. Thus, these drug-loaded microneedles serve as a multifunctional dressing, offering a promising novel strategy for wound repair.
Chronic suppurative otitis media (CSOM) is a leading cause of hearing loss and otorrhea, and when associated with cholesteatoma, it can pose a serious threat to patients' lives. This study aims to identify differences in tissue metabolites between patients with CSOM, both with and without cholesteatoma. Metabolomic profiles were measured in tissue samples from 42 surgically treated CSOM patients (35 with cholesteatoma, 7 without cholesteatoma). Significantly altered metabolites associated with CSOM were identified using a non-targeted metabolomics approach and a targeted metabolomics approach. The 42 patients were divided into screening and validation sets. The non-targeted analysis revealed 484 distinct differential metabolites and 32 metabolic pathways that differed between CSOM with and without cholesteatoma in the screening set. Targeted metabolomics confirmed that levels of azobenzene and marimastat in the validation set exhibited trends similar to those observed in the non-targeted analysis. Azobenzene and marimastat were found to be associated with the differences between CSOM with and without cholesteatoma, as well as with bone erosion in the middle ear. This study identified novel potential metabolic pathways and metabolites, providing insights into their possible roles in the inflammatory processes and bone erosion associated with CSOM and cholesteatoma.
Tissue engineering is a great alternative to repair and regenerate damaged tissues and organs. Hydrogels are promising materials for tissue repair, but optimizing their various functions—such as adhesion, mechanical properties, and vascularization—to suit the complexity of different organs and tissues remains a significant challenge. In this study, we explore a tough and adhesive polydopamine (PDA)-silk-polyacrylamide (PAM) hydrogel inspired by the mussel-inspired adhesion of PDA and the vascularization potential of silk. Through a Schiff base reaction, self-polymerization occurs between the free dopamine and the conjugated dopamine on the silk chains, resulting in the formation of a PDA/silk prepolymer. The presence of PDA in the prepolymer endows the resulting PDA-silk-PAM hydrogel with excellent adhesiveness, strong mechanical properties, and good water absorption. By adjusting the degree of crosslinking, the hydrogel also demonstrates impressive deformability, making it suitable for engineering thicker and more complex tissues and organs. Moreover, benefiting from the vascularization capabilities of silk and the adhesive properties of PDA, the PDA-silk-PAM hydrogel effectively promotes vascularization and accelerates wound healing in full-thickness skin wounds on the backs of Sprague-Dawley rats. Overall, our study provides a straightforward approach to create versatile medical hydrogel with strong potential for clinical applications.
Hydrogel patches have been serving as powerful tools for wound healing. Scientific attention in this field is focused on imparting the patches with novel structures, functions, and actives for promoting wound healing. In this paper, we have developed an innovative hydrogel patch with hierarchical structure and spatiotemporal actives release for efficient wound healing. This hydrogel patch was achieved by integrating asiatic acid (AA)-loaded pollens with chlorogenic acid (CA)-containing gelatin methacryloyl (GelMA) hydrogel. The high specific surface area and nanoporous structure of the pollens-integrated GelMA promote efficient loading and release of CA and AA, respectively. In wound treatment, the outer layer of GelMA first releases CA to fight infection. With the gradual degradation of GelMA, the pollens are exposed to the wounds and released AA, intensifying anti-inflammatory effects and promoting wound healing. These features indicate that this pollen-integrated hydrogel patch significantly accelerates the wound healing process in a spatiotemporal responsive manner, demonstrating great potential for clinical applications.
Due to the ability to precisely control and manipulate fluids at the microscale, microfluidics provides unmatched advantages such as reduced sample size, rapid analysis, and enhanced sensitivity. Microfluidic technology has emerged as a revolutionary approach in pediatric healthcare, offering innovative solutions for diagnostics, monitoring, and treatment. This review presents a comprehensive overview of the recent advancements and future directions of microfluidic technology in the field of pediatrics. We begin with a brief introduction of several types of microfluidic devices that are more common in the pediatric field. Then, the substantial advances in biomedical applications of microfluidics in pediatric healthcare are explored, encompassing diagnosis, research, and treatment. Finally, challenges and limitations such as material selection, device standardization, stability, and regulatory considerations are also discussed that must be addressed to increase the utilization of microfluidics in the pediatric clinical field. Overall, this review underscores the transformative potential of microfluidics to improve the quality of healthcare and outcomes for pediatric patients, while also highlighting the opportunities for future research and development in this burgeoning field.