Biomaterials research最新文献

Fluorescence imaging is a promising intraoperative technique for gastric cancer surgery, enabling clear visualization of surgical margins and detection of occult lesions. However, the lack of near-infrared (NIR) fluorescent probes specifically targeting gastric tumors and normal tissues remains a limitation. To address this, we developed a dual-channel imaging strategy using IR-780 (800 nm) for tumor detection and ESS65-Cl (700 nm) for normal gastric tissue identification. We evaluated their specificity in human gastric epithelial (GES-1) and cancer (SGC-7901) cells, confirming selective uptake: ESS65-Cl in normal gastric cells and IR-780 in tumor cells. In subcutaneous and orthotopic xenograft models, dual-channel imaging allowed simultaneous visualization of tumors and surrounding tissues in distinct colors. Pharmacokinetic analysis revealed that ESS65-Cl achieved a stomach signal-to-background ratio of 3.3 by 48 h, while IR-780 exhibited a tumor-to-background ratio of 4.0, demonstrating high targetability. Moreover, biodistribution studies confirmed efficient clearance of both agents. When combined, these fluorophores enabled precise intraoperative differentiation between gastric tissues and tumors. This approach holds substantial potential for improving surgical accuracy in gastric cancer resection, particularly in defining proximal esophageal margins and gastrectomy boundaries. By enhancing real-time tissue discrimination, dual-channel NIR imaging may increase surgical success rates and improve patient outcomes.

[This corrects the article DOI: 10.1186/s40824-022-00251-z.].

Traditional polymer-based arteriovenous grafts (AVGs) for hemodialysis access suffer from poor long-term patency, high reintervention rates, and susceptibility to infection. In contrast, decellularized tissue-engineered vascular grafts (dTEVGs) demonstrate improved patency, long-term durability, and resistance to infection. However, vascular stenosis and occlusion caused by anastomotic intimal hyperplasia (AIH), as well as vascular stiffening and calcification from excessive perigraft fibrosis (PGF), remain major challenges in the clinical use of dTEVGs for AVGs. M2 macrophage infiltration plays a key role in the biological processes of pro-regeneration and the clinical application of dTEVGs. However, in elastin-rich dTEVGs commonly used clinically, the elastic fiber layers form a barrier to cell infiltration, potentially limiting their biological functions. Therefore, the specific impact of M2 macrophage infiltration on dTEVGs in AVGs remains unclear. Through parallel analysis of human explants and a rat dTEVG-AVG model, we found that M2 macrophage infiltration predominates in dTEVGs, and this infiltration is associated with AIH and PGF. Furthermore, IL-4-loaded poly(lactic-co-glycolic acid)/gelatin methacryloyl delivery systems selectively enhanced M2 macrophage polarization, while sustained M2 macrophage infiltration triggered TGF-β1/Smad3-dependent myofibroblast activation, leading to increased AIH and PGF. Pharmacological inhibition of Smad3 phosphorylation selectively alleviated AIH and PGF without affecting M2 macrophage recruitment or other associated biological functions. These findings reveal the dual role of M2 macrophages in dTEVGs for AVGs, which, while promoting pro-regeneration, unexpectedly accelerate AIH and PGF. A targeted Smad3 inhibition strategy selectively alleviates AIH and PGF caused by M2 macrophage infiltration, without compromising M2 macrophage-associated functions.

Bionically designed gradient microporous scaffolds have garnered considerable attention in orthopedics and bone tissue engineering for their ability to replicate the gradual pore transition from cortical to trabecular bone, thereby integrating mechanical strength with biological functionality essential for bone regeneration. However, the immune-inflammatory response induced by biomaterial implantation can impair osseointegration, potentially leading to chronic inflammation or implant failure. To address this limitation, the present study utilized selective laser melting to fabricate a biomimetic gradient microporous titanium alloy scaffold based on a triply periodic minimal surface architecture (pore size: 650 to 350 μm), with solid nonporous scaffolds (0 μm) and uniform microporous scaffolds (500 μm) serving as controls. The study comprehensively evaluated the role of the gradient scaffold in both osseointegration and immune modulation. Mechanical testing confirmed that the gradient scaffold possessed an elastic modulus well matched to that of bone tissue, thereby mitigating stress shielding. In vitro assays revealed that, relative to the control scaffolds, the gradient scaffold more effectively promoted macrophage polarization toward the M2 phenotype while enhancing the osteogenic differentiation capacity of bone marrow mesenchymal stem cells. Subsequent in vivo experiments demonstrated that the gradient microporous titanium alloy scaffold attenuated local inflammatory responses and facilitated new bone formation. Collectively, these findings provide compelling evidence for the dual role of titanium alloy gradient biomimetic microporous structures in immune regulation and osseointegration, offering critical insights for the optimization of scaffold designs in bone tissue regeneration.

Recently, biomaterials have been developed for ex vivo expansion of hematopoietic stem cells (HSCs). HSCs exist in highly specialized niches in the bone marrow and are extremely sensitive to their microenvironment; therefore, this review focuses on the architecture of biomaterials and its effects on HSC culture. Herein, we describe the chemical and physical components of the HSC's niche that can be used to inform the design of biomaterials. We then summarize the effects of surface topography, structural properties, and chemical composition of biomaterials on HSC culture. Subsequently, we identify the gaps and challenges in HSC culture, informing the potential future directions that studying HSC culture on biomaterials can take.

Triple-negative breast cancer (TNBC) remains a formidable clinical challenge owing to its aggressive behavior, immunosuppressive tumor microenvironment, and lack of effective targeted therapies. To address these limitations, we developed a magneto-photo-acoustic responsive nanoplatform (MnFe₂O₄-erastin-perfluoropentane nanoparticles [MEPNPs]). This nanoplatform features 3-tiered therapeutic innovations: (a) Multimodal imaging-guided precision therapy: The superparamagnetic property of MnFe₂O₄ enabled magnetic resonance and photoacoustic imaging, allowing real-time visualization of tumor margins. (b) Spatiotemporally controlled ferroptosis activation: Magnetic targeting enhanced the tumor accumulation of MEPNPs, while near-infrared irradiation triggered perfluoropentane vaporization for burst erastin release. This dual strategy combinationally suppressed glutathione peroxidase 4 and amplified the accumulation of lipid peroxides, achieving the amplification of ferroptosis. (c) Immunogenic tumor microenvironment reprogramming: MEPNP-induced immunogenic cell death promoted dendritic cell maturation and CD8⁺ T-cell infiltration, effectively converting immunologically "cold" TNBC tumors into "hot" phenotypes. In TNBC models, MEPNP treatment elicited remarkable therapeutic outcomes: primary tumor suppression, reduction in lung metastasis, and an extended median survival period exceeding 45 d. The transcriptome sequencing results showed that there were 6,198 differentially expressed genes in the treatment group. These included the up-regulation of ferroptosis drivers such as SLC39A14, as well as the down-regulation of antioxidant regulators such as SLC7A11 and SLC3A2. Additionally, Kyoto Encyclopedia of Genes and Genomes pathway analysis confirmed that the "ferroptosis" and "T-cell differentiation" pathways were specifically activated. This work establishes a novel "theranostic-immunomodulatory" paradigm that integrates magnetic targeting, ferroptosis potentiation, and immunogenic-cell-death-mediated immune memory. By orchestrating physical energy conversion, MEPNPs provide a spatially focused and immunologically amplified strategy to overcome TNBC therapeutic resistance.

Coronary heart disease (CHD) remains a leading etiology of cardiovascular mortality globally. Endothelial dysfunction is now well-documented as the incipient pathological event in coronary atherosclerosis, with endogenous nitric oxide (NO) and nitric oxide synthase playing pivotal roles in regulating endothelial homeostasis via diverse signaling cascades. Over the past several decades, the pleiotropic functions of NO in cardiovascular physiology and pathophysiology have sparked substantial research interest in leveraging exogenous NO delivery strategies for atherosclerotic interventions. Beyond conventional NO-based pharmacotherapies, notable advancements have been achieved in the development of NO-releasing platforms and donor systems capable of spatiotemporally controlled and sustained NO delivery to target vascular tissues. This comprehensive review synthesizes current understanding of (a) the dual roles of endogenous NO in maintaining cardiovascular health and mediating pathological processes, (b) the enzymatic regulation of NO biosynthesis and its downstream signaling networks, and (c) the emerging translational potential of NO-based biomaterials in atherosclerotic management. Particular emphasis is placed on evaluating novel NO-donor systems and bioengineered constructs that exhibit therapeutic efficacy in preclinical models. Collectively, this analysis underscores the critical importance of NO-based biomaterials in advancing precision medicine approaches for CHDs, with implications for both diagnostic innovation and therapeutic optimization.

Although an increasing number of studies focus on treating chronic obstructive pulmonary disease (COPD) through the gut-lung axis and immunomodulation, its underlying mechanisms remain poorly understood. Previous research has shown that Qifenggubiao granules (QFGB) exhibit obvious clinical efficacy in treating allergic rhinitis and chronic cough, demonstrating excellent antioxidant and anti-inflammatory properties. However, whether it can alleviate COPD by inhibiting ferroptosis remains unclear. Additionally, its immunomodulatory mechanisms in gut microbiota dysbiosis-related inflammation require further investigation. In this study, we found that QFGB not only suppresses oxidative stress but also inhibits ferroptosis by reducing lipid peroxide levels and increasing the expression of glutathione peroxidase 4 and xCT. The authors also discovered that QFGB significantly alleviates pulmonary dysfunction in COPD animal models by regulating macrophage polarization and remodeling the inflammatory immune microenvironment, thereby suppressing inflammation. Furthermore, 16S ribosomal RNA sequencing and quantitative reverse transcription polymerase chain reaction analysis confirmed that QFGB modulates gut microbiota composition and bidirectionally regulates macrophage polarization in lung and intestinal tissues. These findings have been further validated in animal models of inflammatory bowel disease (IBD), demonstrating that QFGB can alleviate inflammation in IBD mice. This study demonstrates that QFGB can not only inhibit oxidative stress and ferroptosis in COPD but also regulate gut microbiota homeostasis and remodel the inflammatory microenvironment by modulating macrophage polarization via the gut-lung axis. The drug alleviates the severity of COPD and promotes functional recovery of the lung-gut organ axis. These findings have been further validated in animal models of IBD, demonstrating that QFGB can alleviate intestinal inflammation in mice.

Atherosclerosis is a cardiovascular disease that involves complex and multifactorial processes that are instigated from endothelial dysfunctions. In this review, we address endothelial dysfunction in atherosclerosis and the mechanisms, where they are characterized by structural and functional alterations in endothelial cells (ECs), as caused by inflammation, oxidative stress, or disturbed shear stress. In particular interest, we provide a comprehensive overview of the experimental models (in vitro and in vivo) used to investigate endothelial dysfunction, specifically the role of ECs in atherosclerosis. Finally, current therapeutics, for example, pharmacological interventions, cell and gene therapies, and nanomedicine, are introduced, along with emerging technologies for advanced treatment of atherosclerosis. This review will help readers better understand current scientific findings, experimental models, and technologies in an effort to decipher the mechanisms of atherosclerosis and to advance therapeutic interventions.

Mesenchymal stem cells (MSCs) used for cell-delivery-based therapy also undergo considerable external stresses upon entering the recipient site in the body. Here, we sought to develop a cell-protective barrier on the MSC surface that protects against stress-induced damage from physical external stresses. The barrier was fabricated from gelatin and hyaluronic acid (HyA) using a layer-by-layer (LbL) technique. In addition to assessing the stability and biological properties of extracellular matrix (ECM)-coated human bone marrow-derived MSCs (hMSCs) produced using the LbL, we also evaluated the cell-protective effects of this coating against 2 external stresses: low-attachment conditions and mechanical force induced by injection. Cell biological and morphological surface changes accompanying cell surface coating were analyzed using fluorescence-activated cell sorting and scanning electron microscopy. Viability and cell cycle characteristics were not substantially different between bare hMSCs and ECM-coated hMSCs with different numbers of layers after 7 days in culture. Stemness was also maintained, as reflected in >97.3% expression of positive markers and <0.5% expression of negative markers in 6-layered ECM-coated hMSCs, termed ECM-hMSCs. ECM-hMSCs showed 62.1% decrease in cell damage and 50.6% increase in DNA content after 3 days under low-attachment conditions. In addition, ECM-hMSCs injected at 100 and 200 kPa showed 27.2% and 41.8% higher viability, with damaged cells decreased by 54.9% and 45.6%, respectively, compared to bare hMSCs. These results show that LbL coating of hMSCs with gelatin and HyA does not impair the function of hMSCs and can physically protect cells from low-attachment conditions and the mechanical force associated with injection.