Biomaterials research最新文献

Periodontitis, a highly prevalent chronic inflammatory disease globally, faces substantial challenges in achieving periodontal tissue regeneration, necessitating the development of novel therapeutic strategies. Chinese herbal medicine-derived extracellular vesicles (CHMEVs), natural nanoscale carriers enriched with bioactive components from medicinal plants, exhibit unique therapeutic advantages in tissue repair. Here, we isolated extracellular vesicle-like particles from Paris polyphylla var. yunnanensis leaves (PP-L-EVLPs), a traditional Chinese medicinal herb native to Yunnan, and systematically evaluated their therapeutic potential for periodontal regeneration. PP-L-EVLPs were efficiently internalized by periodontal ligament stem cells (PDLSCs), enhancing their proliferation, migration, and osteogenic differentiation through up-regulation of ALP, RUNX2, and OPN. PP-L-EVLPs significantly suppressed the protein expression levels of lipopolysaccharide-induced interleukin-6 (IL-6) and IL-8 in PDLSCs. In a rat alveolar bone defect model, PP-L-EVLPs significantly promoted bone regeneration, as evidenced by micro-computed tomography, histology, and immunohistochemistry. Biosafety evaluations revealed no histopathological abnormalities or genotoxicity in major organs of Sprague-Dawley rats treated with PP-L-EVLPs. This study is the first to confirm that PP-L-EVLPs exhibit cell migration-promoting, anti-inflammatory, and osteogenic activities with excellent biosafety, offering a novel natural nano-based therapeutic strategy for periodontitis treatment.

Cancer immunotherapy has emerged as a transformative strategy for treating malignancies by harnessing the body's immune system. However, its clinical efficacy is often limited by the complex and immunosuppressive nature of the tumor microenvironment (TME), which poses substantial barriers to therapeutic success. The TME comprises a variety of components, including immune cells, cancer-associated fibroblasts, abnormal vasculature, extracellular matrix, and soluble mediators that collectively support tumor progression, suppress immune surveillance, and contribute to treatment resistance and poor prognosis. Recent advances in nanotechnology have introduced engineered nanomaterials as promising tools to modulate the TME and enhance the outcomes of cancer immunotherapy. These nanomaterials can be precisely engineered to interact with specific elements of the TME, enabling localized delivery, reduced systemic toxicity, and improved therapeutic efficacy. This review provides a comprehensive overview of the role of engineered nanoparticles in targeting both cellular and noncellular components of the TME. It highlights the capacity of nanocarriers to reprogram tumor-associated immune cells, including T cells, dendritic cells, natural killer cells, and tumor-associated macrophages, as well as their ability to target cancer-associated fibroblasts, remodel tumor vasculature, degrade the extracellular matrix, and modulate immunosuppressive mediators. By exploring these multifaceted interactions, we illuminate how rationally designed nanomaterials can reshape the tumor landscape to restore immune function and enhance immunotherapeutic efficacy. Finally, the review addresses current challenges, safety considerations, and future directions necessary to translate these innovations into clinically viable therapies.

Multidrug-resistant (MDR) pathogens such as methicillin-resistant Staphylococcus aureus (MRSA) pose a substantial challenge to global public health, particularly because of chronic and persistent infections associated with bacterial biofilms, which call for safe and innovative therapeutic strategies. Here, we present a novel antibiofilm system inspired by the preferential uptake properties of isogenous bacterial membrane vesicles (MVs). This system employs vancomycin (VAN) for bacterial killing, while MVs act as delivery vehicles to increase VAN penetration into biofilms. VAN@^ΔagrMVs demonstrated sustained drug release and improved VAN accessibility within biofilms. Treatment with VAN@^ΔagrMVs considerably reduced the number of planktonic MRSA strain USA300 cells and effectively eradicated MRSA biofilms in vitro. RNA sequencing revealed substantial alterations in genes associated with bacterial cell wall biosynthesis, global regulators, virulence factors, and biofilm formation. Treatment with VAN@^ΔagrMVs substantially reduced the MRSA burden within biofilms in vivo. Safety evaluation demonstrated the avirulent properties of the VAN@^ΔagrMVs, highlighting its potential for clinical application. Overall, this study offers a promising alternative for MRSA biofilm eradication, providing a viable strategy to combat chronic infections caused by MDR biofilm-forming pathogens.

Soft-tissue sarcoma (STS) is a rare and heterogeneous group of cancers with more than 100 histological subtypes, which makes biological understanding and therapeutic development particularly challenging. Patient-derived tumor organoid models have transformed cancer research by providing patient-representative preclinical platforms, yet their application in STS has been limited because of low establishment efficiency. To address this problem, a gelatin-based culture protocol was developed to enhance critical cellular processes, including mitochondrial function and cell adhesion, which are essential for organoid self-organization. Using this optimized system, patient-derived tumor organoids were successfully established from representative STS subtypes, such as dedifferentiated liposarcoma and leiomyosarcoma. These organoids retained the histopathological architecture and molecular characteristics of the original tumors and reflected subtype-specific oncogenic pathways, mitochondrial dynamics, and lipid metabolic signatures. Our established gelatin-based organoid culture system enables efficient establishment of patient-derived organoids from representative STS subtypes, faithfully preserving their histopathological and molecular characteristics. These models recapitulate subtype-specific oncogenic pathways, mitochondrial dynamics, and lipid metabolic signatures, providing a robust and clinically relevant preclinical platform for investigating sarcoma biology and developing personalized therapeutic strategies.

NIR-II small-molecule-based bimodal imaging systems accurately unify diagnosis and therapeutics for precision tumor therapy, which is attributed to their easily modifiable structures, high potential biocompatibility. In particular, the highly efficient photodiagnostic agent with high light-to-heat transformation performance and fluorescence/photoacoustic imaging (FLI/PAI) with the range of near-infrared-II (NIR-II; 900 to 1,700 nm) has emerged as a popular research topic. This study reported a series of Aza-boron-dipyrromethenes (Aza-BODIPY) dyes (Aza-A/B/C) with donor-acceptor structure through the introduction of diethylaminobenzene (electron donor) and (iso)quinoline (electron acceptor) into the Aza-BODIPY backbone. Compared to Aza-A/B, the enhanced light trapping ability, the decreased NIR-II fluorescence emission performance, and poor reactive oxygen species generation capacity made Aza-C as an optimal photothermal agent. Through 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DSPE-mPEG₂₀₀₀) capping, the as-prepared Aza-C nanoparticles (Aza-C NPs) showed excellent biocompatibility, super stability, outstanding light-to-heat transformation performance (ƞ = 58.2%), as well as concentration-dependent linear FL/PA signals, which guaranteed that Aza-C NPs could be successfully utilized for NIR-II FLI/PAI-directed efficient photothermal therapy (PTT) of cervical tumor, with high tumor inhibition rates of over 90%. Introducing diethylaminobenzene and (iso)quinoline to Aza-BODIPY backbone help to construct NIR-II Aza-C dye for NIR-II FLI/PAI-directed efficient tumor PTT. This novel approach offers a promising avenue toward the ablation of tumors in deep tissues.

Cancer-associated fibroblasts (CAFs), one of the most substantial constituents of the pancreatic tumor microenvironment, exhibit far greater heterogeneity and phenotypic plasticity than it was previously recognized. Accordingly, distinguishing between CAF subpopulations and their functional roles in pancreatic tumorigenesis has become increasingly important. Additionally, as the importance of the therapeutic approach increases, interests in technologies capable of efficiently differentiating between normal fibroblast subpopulations and pathologic CAFs also grow. Label-free imaging and analytical technologies that do not require fluorescent labeling or other preprocessing steps offer a promising alternative to conventional invasive cell analysis. Here, we employed Raman spectroscopy to chemically characterize human primary pancreas stellate cell (HPaSC), inflammatory CAF (iCAF), and myofibroblastic CAF (myCAF) derived from HPaSC at the cellular level for molecular profiling. As a result, we successfully compared the distinctive biological and chemical properties of each fibroblastic subtype. These Raman spectrum findings were validated by transcriptomic and lipidomic analysis. Our molecular profiling demonstrates that CAF subpopulations can be quantitatively distinguished based on their intrinsic chemical signatures, offering valuable insights into identifying and characterizing CAFs without relying on fluorescence or specific biomarkers. These multivariate spectral analyses enable subtype classification in 95% accuracy combined with partial least squares discriminant analysis (PLS-DA). This result demonstrates that CAF subtypes can be quantitatively distinguished using their intrinsic molecular signature, which support potential in pancreatic cancer research and therapeutic development.

The tumor microenvironment (TME) is a complex ecosystem where interactions between tumor cells, immune cells, and microbes notably influence cancer progression and response to therapy. Tumor-associated macrophages (TAMs), which are crucial components of the TME, exhibit remarkable plasticity, adapting their functions in response to signals from both the tumor and its microbiota. Microbes-including bacteria, viruses, fungi, and their metabolites-modulate multiple aspects of TAM biology, from polarization and metabolism to immune modulation, thereby influencing tumor progression and immune evasion. This review focuses on the mechanisms through which microbes shape TAM responses, particularly in the context of cancer immunotherapy. Emerging therapeutic strategies leverage these microbe-TAM interactions using engineered microbes, oncolytic viruses, and microbial nanomaterials to reprogram TAMs and enhance antitumor immunity. Although formidable challenges remain, including spatial and temporal heterogeneity, mechanistic complexity, and safety concerns, these innovative approaches hold the potential to revolutionize cancer treatment. By targeting the microbe-TAM axis, this therapeutic strategy offers a promising avenue for overcoming resistance and improving the effectiveness of cancer immunotherapy.

Nanoparticles are increasingly utilized for their potential in targeted drug delivery, highlighting the need for innovative approaches to enhance therapeutic and regenerative outcomes. This study investigated zinc- and iron-ion-releasing nanoparticles (ZFNs) for their ability to simultaneously deliver zinc (Zn) and iron (Fe) ions, aimed at boosting the efficacy of human mesenchymal stem cells (hMSCs) in wound healing. Engineered for pH-sensitive degradation, ZFNs enable the controlled intracellular release of these ions following endocytosis by hMSCs. Our in vitro findings include favorable release kinetics and the absence of toxicity. We observed that dual-ion delivery via ZFNs markedly modulated the key zinc transporter gene expression and enhanced the angiogenesis- and migration-related gene expression in hMSCs. This activity correlates with the activation of mitogen-activated protein kinase and AKT signaling pathways, essential for processes such as cell migration and proliferation, thereby supporting tissue regeneration. Indeed, changes in the secretion profiles of hMSCs treated with ZFNs were found to enhance the migratory and regenerative capacities of both fibroblasts and keratinocytes. In vivo experiments confirmed that hMSCs integrated with ZFNs accelerate wound healing and upregulate the expression of essential skin barrier proteins. Collectively, these findings position ZFNs as a promising tool for enhancing stem-cell-mediated tissue regeneration, with potential widespread applications in clinical stem cell therapies.

Astaxanthin (AST), a potent bioactive compound known for its exceptional antioxidant, anti-inflammatory, and anti-apoptotic capacities, has been widely applied in advanced biomedical domains, including regenerative tissue engineering and targeted drug delivery systems. However, its chemical instability limits broader applications. To address this issue, various multifunctional biomaterials, such as nanoliposomes, nanoparticles, glass microspheres, and algal calcium beads, have been employed to stabilize AST and enhance its therapeutic efficacy. This review provides a comprehensive overview of AST, examines its mechanisms of action, and discusses the development and biomedical applications of AST-based biomaterials. We demonstrate the excellent properties and potential applications of these biomaterials in various biomedical contexts, outline existing challenges, and propose future directions to optimize their design and advance their clinical translation.

Acute lung injury (ALI) is one of the complications of sepsis, and macrophages play an important role in ALI. The aim of this research was to investigate the effects of epidermal growth factor receptor (EGFR) monoclonal antibody-modified chemokine (C-X-C motif) ligand 8 (CXCL8) overexpression of macrophage (CXCL8@M)-derived exosomes miR-126a-3p (EGFR@CXCL8@exo-miR-126a-3p) on sepsis ALI. CXCL8@M was obtained via macrophage infection of CXCL8 plasmid, and CXCL8-M-exo was obtained via an exosome extraction kit. In addition, hsa-miR-126-3p agomir [a specially chemically modified microRNA (miRNA) mimic, named miR-126-3p] was loaded in CXCL8@M-exo to form CXCR8@exo-miR-126a-3p via electroporation technology. Further, EGFR@CXCR8@exo-miR-126a-3p was obtained via EGFR monoclonal antibody-modified CXCR8@exo-miR-126a-3p. Lipopolysaccharide (LPS)-induced ALI models were used to evaluate the role and mechanism of EGFR@CXCR8@exo-miR-126a-3p on ALI. Single-cell sequencing and miRNA chip results showed that miR-126a-3p was mainly expressed in pulmonary macrophages and markedly decreased, while single-cell sequencing and immunofluorescence results showed that EGFR was expressed and significantly elevated in macrophages in ALI mice. miR-126a-3p and EGFR siRNA significantly inhibited polarization of M1 macrophage. The imaging results of small animals showed that EGFR@CXCL8-exo-miR-126a-3p has obvious macrophage targeting. The results showed that EGFR@CXCR8@exo-miR-126a-3p significantly inhibited M1 macrophage and increased Treg cells to exert anti-inflammatory effects. The mechanism of EGFR@CXCR8@exo-miR-126a-3p on ALI is mainly via inhibition of PIK3R2/NLRP3 signaling pathway and ferroptosis. This study provided a new treatment method for ALI.