Smart medicine最新文献

Peripheral nerve injury (PNI) presents a significant clinical challenge due to the intrinsic limitations of nerve regeneration and poor functional recovery. Although nerve guidance conduits (NGCs) offer a promising alternative to autografts, their therapeutic efficacy is often constrained by insufficient bioactivity and electrical conductivity. To address these dual deficiencies, we engineered an electroactive living nerve conduit by integrating silk sericin (SS)-modified carbon nanotubes (SCNTs) with adipose-derived stem cells (ADSCs). The SCNTs serve as a conductive scaffold, whereas the ADSCs provide a sustained release of neurotrophic factors. This design creates a synergistic microenvironment to promote neuronal maturation and axonal regeneration. In an experimental rat model featuring a 10-mm sciatic nerve gap, ADSC/SCNT/RAM NGCs demonstrated regenerative performance comparable to autografts, facilitating axon connection and recovery of motor functions. Histological assessment revealed that the implanted ADSC/SCNT/RAM NGCs promoted the most extensive nerve and axon regeneration among all groups, as evidenced by the significantly higher counts of S100 calcium-binding protein B (S100-β)-positive cells (10,152 ± 986.00) and Neurofilament Protein 200 (NF200)-positive cells (11,517 ± 795.70). Corroborating these histological findings, functional analysis demonstrated that the ADSC/SCNT/RAM group achieved the highest sciatic nerve function index (SFI) at 12 weeks post-surgery (-58.06 ± 1.46), a value comparable to the Autograft group (-57.73 ± 1.80). This strategy proposes a promising tissue-engineered alternative to autografts for nerve repair.

Immune checkpoint inhibitors (ICI) have demonstrated prolonged efficacy in certain melanoma patients, yet a significant portion of patients do not experience clinical improvement, with the mechanisms underlying this resistance still not fully understood. Using established cell markers, we partitioned the single-cell transcriptome into clusters, finding a notable link between NK cells and patient response to immunotherapy. We further identified four distinct subpopulations of NK cells, profiling marker gene sets and unique biological functions associated with each subpopulation. This analysis provides insights into the trajectory of NK cell development and differentiation, along with identifying the transcription factors driving these processes. The study pinpointed NK cluster 01 as pivotal in influencing patient sensitivity and prognosis during immunotherapy. Single-cell transcriptome and spatial transcriptomics (ST) analysis revealed the proximity of NK cluster 01 cells to melanoma cells, hinting at a potential regulation of cell-cell interaction via the IFN-II signaling pathway network. ST analysis revealed the spatial arrangement and interaction of NK cluster 01 cells with melanoma cells. This study explores the feasibility of targeting NK cluster 01 cells with small molecule drugs via molecular docking, offering a promising approach to bolster the clinical utility of NK cell therapy. We comprehensively analyze the heterogeneity of NK cells within melanoma, elucidate the potential regulatory interactions between NK cells and other microenvironmental components, and establish a basis for the future clinical utilization of distinct NK cell subsets as therapeutic targets.

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.

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.

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.

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.

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.

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.

Wound healing has been a continuous critical focus in clinical practice, posing the ongoing challenges and burdens to patients. Current attempts tend to develop multi-drug loaded patches with spatial design. Herein, we present a multifunctional microneedle patch that integrates different drugs into separated regions for wound treatment. The microneedle patch is composed of silk fibroin-methacryloyl (SilMA) as the base, loaded with silver nanoparticles (AgNPs) and has gelatin methacryloyl (GelMA) tips loaded with vascular endothelial growth factor (VEGF). The backing is endowed with antimicrobial properties by AgNPs act as an antimicrobial barrier against bacterium invasion. In addition, the tips encapsulated with VEGF can effectively promote cell proliferation and angiogenesis, which is favorable for wound repair. Based on these characteristics, such an integrated microneedle system significantly prevented bacterial infection and promoted wound healing in vivo. Therefore, it is conceived that such a system can find more practical values in wound healing and other fields.

Allergic contact dermatitis (ACD) is an inflammatory dermatitis with a high morbidity and recurrence rate. Scientific attention is focused on the development of safe and comfortable therapeutics of ACD. Herein, we propose a natural matrine-integrated pollen delivery system for the ACD treatment. Sunflower pollens were collected and defatted to serve as adhesive drug carriers for matrine. Specifically, the exquisite porous and hollow structures of the pollen shells can absorb matrine and realize the sustained drug release. Besides, the prickly surface morphology can strongly adhere to the inflamed skin sites, which can prolong the duration of the drug. By utilizing them in an ACD model and an acute pruritus model of mice, we have demonstrated that these matrine-integrated pollen shells can decrease the swelling degree of mice ears and weight loss, down-regulate inflammatory response, and improve the scratching times. These results indicate that our matrine-integrated pollen delivery systems have great potential to serve as natural topical preparations for skin disease therapy.