Biomaterials research最新文献

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.

Early immune homeostasis at the biomaterial-tissue interface is a critical engineering challenge for osseointegration success. While strontium (Sr)-modified biomaterials exhibit advantages in enhancing osseointegration, the immunomodulatory effects of localized Sr release, particularly on upstream monocytes, remain unelucidated. This study aims to delineate Sr-reprogrammed monocyte subset dynamics and the underlying mechanism. Here, we engineered Sr-doped sandblasted, large-grit, and acid-etched (Sr-SLA) titanium implants. Sr-SLA implants ameliorated the early inflammatory microenvironment and promoted osseointegration. To decipher the Sr-modulated immune microenvironment, we employed single-cell RNA sequencing, which revealed that monocytes constituted the largest proportion of cells surrounding implants, with subset distribution correlating with osteogenic efficiency. Notably, Sr-SLA implants suppressed the activation of pro-inflammatory classical monocytes (Ly6C^hi), with high transient receptor potential melastatin 2 (TRPM2) and nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain-containing 3 (NLRP3) expression, while promoting the expansion of regenerative nonclassical monocytes (Ly6C^lo), exhibiting low TRPM2 and NLRP3 levels. Further validation demonstrated that Sr ions inhibited NLRP3 inflammasome activation in monocytes via blocking TRPM2 expression and calcium influx, leading to reduced pro-inflammatory cytokine (interleukin-1β and interleukin-18) secretion. Meanwhile, a conditioned medium from Sr-SLA-cultured monocytes exerted robust osteogenic potential by markedly facilitating bone marrow mesenchymal stromal cells' osteogenic differentiation, due to a Sr-reshaped cytokine profile. Moreover, in vivo study corroborated that monocyte depletion impaired osseointegration, underscoring its indispensable role in implant-mediated bone regeneration. Collectively, Sr-SLA implants reprogrammed monocyte subsets via the TRPM2-Ca²⁺-NLRP3 axis, reshaping the early inflammatory microenvironment to enhance osseointegration. This study establishes a cascade linking material properties, early immune response, and bone regeneration, providing an engineerable target for designing immunomodulatory biomaterials.

Respiratory virus infections continue to pose a substantial global health challenge, requiring effective prophylactic and therapeutic strategies. Type III interferon (IFN-λ) has shown promise as an antiviral agent that strongly inhibits viral replication while minimizing systemic inflammation. Intranasal administration of IFN-λ allows easy access to the respiratory mucosa, enhancing localized antiviral responses. However, clinical application of IFN-λ is hindered by rapid mucociliary clearance, limited mucosal adhesion, and susceptibility to proteolytic degradation. Here, we develop nanoliposomes that can deliver IFN-λ through an intranasal route (NLp@IFN-λ) and act as an effective antiviral. We demonstrate that the nanoliposomes enable efficient penetration of IFN-λ in a mucus-mimicking model while allowing controlled release of the protein in vitro. NLp@IFN-λ treatment could effectively up-regulate interferon-stimulated genes in A549 cells, without inducing cytotoxicity. Finally, in vivo delivery of NLp@IFN-λ through a nasal route demonstrates prolonged retention and reduces viral load in nasal tissues in an infection model with influenza virus. This study demonstrates the potential of NLp@IFN-λ as an effective nasal delivery platform for prophylaxis of respiratory virus infections.

The precise determination of resection margins during head and neck cancer surgery remains an unmet clinical challenge, where balancing complete tumor removal with preservation of healthy tissue is critical. To address this, we developed a dual near-infrared (NIR) fluorescence imaging strategy targeting both tumor cells and the tumor microenvironment (TME) in head and neck squamous cell carcinoma (HNSCC). Armed with 2 small-molecule fluorophores, OCTL14 for tumor-specific imaging and cRGD-ZW800-PEG for TME visualization, we performed real-time intraoperative NIR imaging in a FaDu tongue cancer xenograft model. Fluorophores were administered intravenously, and their targeting efficiency was quantified via time-dependent tumor-to-background ratios (TBRs), with surgical margins validated by histopathology. Our results demonstrated robust detection of cancerous tissue (TBR > 2.0) and surrounding TME (TBR > 1.5) within 4 h post-injection. Histopathology confirmed OCTL14 uptake in tumor cells, while cRGD-ZW800-PEG localized to peritumoral regions and vasculature. This dual-imaging approach offers a promising tool for fluorescence-guided surgery, enabling precise margin delineation to reduce locoregional recurrence and perioperative complications, thereby improving patient outcomes and quality of life.

Ulcerative colitis (UC), a chronic inflammatory bowel disease characterized by recurrent colonic mucosal inflammation, substantially impairs patient quality of life. While photodynamic therapy offers promise for UC treatment, conventional photosensitizers face limitations including poor solubility and inadequate targeting. Here, we developed an orally administered multifunctional nanosystem (CBF@LCP) to remodel dysbiotic gut microbiota and enable synergistic phototherapy. The core comprises reactive-oxygen-species-responsive liposomes, encapsulating our previously established iodinated cyanine photosensitizer CyI, and folic acid with bovine serum albumin via amide bonds (CBF@L). This outer layer is coated with a prebiotic chitosan/pectin shell via layer-by-layer assembly. Following oral administration, CBF@LCP withstands the gastrointestinal tract via pH-dependent contraction. Following gastrointestinal-enzyme-mediated decoating, the exposed CBF@L is internalized by folate-receptor-overexpressing M1 macrophages at colitis sites. Under near-infrared irradiation, CyI executes dual photodynamic therapy/photothermal therapy, ablating pro-inflammatory macrophages while exploiting the oxygen-augmented UC microenvironment to enhance reactive oxygen species generation without exogenous oxygen carriers. Concurrently, the prebiotic shell restores microbial eubiosis by suppressing pathogens and promoting beneficial bacteria. In vivo studies in dextran sulfate sodium-induced colitis models demonstrate that CBF@LCP achieves targeted drug release, mitigates inflammation, reprograms macrophage polarization, preserves intestinal barrier integrity, and activates the phosphatidylinositol 3-kinase/AKT signaling pathway. Gut microbiota and transcriptomic analyses confirm restoration of microbial balance and mucosal healing. This work presents a potent targeted strategy for UC management through microbiota remodeling and oxygen-enhanced phototherapy.

Metabolic reprogramming represents a defining feature of the tumor microenvironment, driving both unchecked proliferation and therapeutic resistance. While conventional single-target metabolic therapies have demonstrated limited efficacy owing to the intrinsic adaptability of tumor cells, recent attention has turned toward natural herbal medicine. Combining broad, multilayered actions with low toxicity, they offer a promising way to modulate tumor metabolism and overcome current therapeutic limits. Herein, this work introduces an Artesunate/Icaritin (ART/ICA) hybrid nanoplatform derived from herbal medicine that employs a multimodal energy depletion strategy for malignant tumor therapy. Coadministration of ICA and ART in a nano-platform produces a mutually reinforcing effect that amplifies inhibition of glucose uptake, strengthens antiangiogenic activity, and intensifies mitochondrial dysfunction, overcoming the limitations of single-pathway interventions. The glutathione-responsive disulfide linkages in the nanomedicine enabled controlled, tumor-selective drug release, enhancing the therapeutic agents' stability and bioavailability. In vitro mechanistic studies supported by RNA sequencing analyses and traditional molecular assays demonstrated that this multimodal approach effectively disrupted cellular energy homeostasis, induced apoptosis, and regulated key metabolic pathways. In vivo evaluations using various tumor models, including hepatocellular carcinoma transgenic mouse models, confirmed significantly enhanced antitumor efficacy, while subcutaneous tumor models showed a tumor inhibition rate exceeding 97%, far surpassing the effects of ART or ICA alone. Furthermore, flow cytometry analyses also confirmed that this strategy modulated the tumor microenvironment by enhancing the infiltration of cytotoxic CD8⁺ T cells and promoting dendritic cell maturation, while the incorporation of a CD47-targeting nanobody further strengthened immune activation and contributed to improved antitumor efficacy.

Although tea consumption has been suggested to affect kidney stone formation, epidemiological evidence remains inconsistent, and the underlying molecular mechanisms are unclear. To assess the association between tea intake and kidney stone risk, we initially conducted a prospective cohort analysis of 481,393 participants from the UK Biobank and a 2-sample Mendelian randomization (MR) analysis. Our findings revealed that heavy tea drinkers (>5 cups/day) had a significantly reduced risk of kidney stones (hazard ratio: 0.79, 95% confidence interval [CI]: 0.72 to 0.86, P < 0.001), and MR analyses confirmed a causal association (inverse variance weighted OR: 0.45, 95% CI: 0.32 to 0.62, P < 0.001). We next explored the effect of epigallocatechin gallate (EGCG), the main bioactive component in tea, on calcium oxalate (CaOx) stone formation. EGCG was found to inhibit the glucose-regulated protein 94/phosphatidylinositol 3-kinase/protein kinase B (GRP94/PI3K/AKT) pathway in human proximal renal tubular epithelial cells, thereby attenuating CaOx crystal-induced oxidative stress and inflammation, and inhibiting crystal-cell adhesion. This finding aligned with the observation that the activated GRP94/PI3K/AKT pathway was positively associated with inflammation-related molecules in renal papillary tissues of CaOx stone formers. Moreover, to enhance renal targeting and therapeutic potential, we synthesized cell membrane-coated EGCG-loaded poly(lactic-co-glycolic acid) (TP-EGCG) nanoparticles, which enhanced renal EGCG delivery and substantially reduced CaOx crystal deposition in a mouse model of CaOx nephrolithiasis. In conclusion, tea consumption protects against kidney stone formation, an effect exerted by EGCG through the GRP94/PI3K/AKT axis, and our novel TP-EGCG nanoparticles show strong potential for targeted prevention and treatment.