Biomaterials research最新文献

Replicating the intricate 3-dimensional architecture and coordinated function of native human myocardium remains a central challenge in cardiac tissue engineering. Here, we present a scaffold-free strategy to fabricate multilayered human cardiac tissues with tunable structural anisotropy and physiologically relevant helical alignment. By integrating biomimetic nanotopographical patterning with a thermoresponsive polymer interface, we generated aligned cardiac cell sheets that could be detached and transferred intact. To ensure robust sheet formation and release, our comprehensive investigation found that a coculture system incorporating human induced pluripotent stem cell-derived endocardial-like endothelial cells was essential for facilitating extracellular matrix deposition and maintaining tissue integrity during detachment, outperforming coculture conditions using other stromal cell types. A glycidyl methacrylate (GMA)-modified polyurethane acrylate substrate functionalized with poly(N-isopropylacrylamide) enabled temperature-controlled release, with 0.5% GMA yielding optimal performance. Stacked cardiac sheets with defined angular offsets were used to engineer 4-layered laminae that mimicked the transmural fiber orientation of the ventricular wall. These helically aligned tissues exhibited enhanced contractile synchrony and superior contractile function compared to unaligned or unpatterned controls, as quantified by vector-based contraction analysis. This work introduces a modular, bottom-up platform for constructing functionally anisotropic cardiac tissues, providing new tools for probing myocardial biomechanics, studying development and disease, and informing regenerative therapies.

Radiation-induced immunological and stromal changes in the pancreatic tumor microenvironment (TME) often develop adaptive radioresistance in clinical. Among these changes, cellular compensatory programmed cell death-ligand 1 (PD-L1) overexpression induced by radiation will promote the adaptive immune evasion, limiting the radiation-mediated antitumor effect. Regrettably, the PD-L1 overexpression will be further potentiated by transforming growth factor-β1 (TGF-β1) that abundantly secreted by irradiated pancreatic stellate cells. This further fosters an immunosuppressive TME, which constitutes one of the key factors contributing to the limited efficacy of combining radiotherapy with programmed cell death protein 1 (PD-1)/PD-L1 blockade in pancreatic ductal adenocarcinoma. To counteract this resistance mechanism, we developed a TME-responsive nanogel (pirfenidone@nanogel-hyaluronidase-anti-PD-L1 [PFD@NGHP]) for rescuing radiosensitization. The PFD@NGHP is composed of a reduction-sensitive core encapsulating pirfenidone and a cationic surface corona of hyaluronidase and anti-PD-L1 antibodies. At the intercellular level, PFD@NGHP effectively inhibited TGF-β1 secretion by about 50% and targeted PD-L1 for antibody-dependent cell-mediated cytotoxicity. In the 3-dimensional stromal microtumors, PFD@NGHP effectively penetrated in stroma (>400 μm in depth), suppressed pancreatic stellate cells, and potentiated radiosensitization. In murine models, PFD@NGHP ameliorated the stroma through TGF-β1 inhibition, subsequently increased T cell infiltration of about 30% CD8⁺ T cells, and amplified the efficacy of PD-L1 blockade. This effect synergized radiotherapy to sustain tumor regression and generate abscopal effects. Collectively, our study demonstrates that PFD@NGHP targets the TGF-β1-PD-L1 axis in a cascading manner, offering a promising clinical strategy to overcome the adaptive radioresistance of irradiated pancreatic ductal adenocarcinoma while providing a potential platform for translational nanomedicine evaluation.

Anaplastic thyroid carcinoma (ATC), as the most malignant pathological type, is prone to local invasion and even distant metastasis with a poor prognosis and a high recurrence rate. Herein, we developed an iron-based metal organic framework (FL@M) as an effective sonosensitizer and biomimetic nanocarrier through the incorporation of lenvatinib (Len) and further coating with homologous tumor cell membranes, achieving the synergistic sonodynamic therapy/chemotherapy for ATC. With the homologous tumor membrane camouflage, FL@M nanoparticles exhibited good biocompatibility, drug loading, and excellent tumor targeting ability both in vitro and in vivo. After absorption, FL@M was decomposed and released Len and Fe³⁺/Fe²⁺. Under ultrasound irradiation, FL@M exhibited excellent sonodynamic effects, rapidly generating a large amount of reactive oxygen species (ROS), which induced oxidative stress and cell apoptosis. In addition, Fe³⁺/Fe²⁺ had good catalase enzyme activity and peroxidase enzyme activity, which could catalyze H₂O₂ to produce O₂ and cytotoxic •OH, respectively, further enhancing the efficacy of sonodynamic therapy (SDT). Moreover, Len exerted a synergistic effect by promoting ROS production during SDT at a lower concentration, which could decrease the occurrence of side effects. In summary, our findings demonstrated that FL@M is a safe and effective metal-organic framework-based nanoplatform to inhibit tumor proliferation, recurrence, and metastasis, offering a promising SDT/chemotherapy combination strategy on thyroid cancer.

Fetal bovine serum (FBS) is commonly used in cell culture but can make up to 60% of total production costs, limiting the scalability of cultured meat (CM). Here, we investigated chicken embryo extract (CEE) as a functional and cost-effective substitute for FBS in culturing porcine muscle satellite cells and generating scaffold-free CM constructs. The 20% CEE + 5% horse serum (HS) medium enhanced myogenic cell growth and development while maintaining paired box 7 expression and up-regulating Myogenin, supporting the coexistence of self-renewing and differentiating states. Oxygen consumption and gene expression analyses revealed reduced oxidative metabolism alongside activation of self-renewal pathways. Transcriptomic analysis showed a specific increase in growth-factor-related genes in 20% CEE + 5% HS group, including CXCL12, TGFB3, and FGF1. Furthermore, 20% CEE + 5% HS differentiation media promoted the extracellular matrix and stable cell sheet organization. Stacked CEE-derived sheets yielded CM constructs with hardness and chewiness levels comparable to those of conventional pork cuts, while maintaining similar springiness and cohesiveness. Our findings show that 20% CEE + 5% HS is a feasible and cost-effective alternative to FBS, allowing for dual cell fate regulation and facilitates structured CM.

Calcium phosphate (CaP) ceramics are widely used in bone regenerative medicine for their osteoconductive properties. Osteogrow-C is a novel device that comprises recombinant human bone morphogenetic protein 6 (rhBMP6) in autologous blood coagulum, utilizing ceramics as a compression-resistant matrix. This study evaluated how CaP granule size and composition affect bone formation and implant integrity in 2 relevant animal models: the rat subcutaneous model and rabbit posterolateral lumbar fusion (PLF) model, over 1 year. The implants in the rat model had varying granule size ranges (74 to 420 μm, 500 to 1,700 μm, 2,360 to 4,000 μm) and compositions [β-tricalcium phosphate (β-TCP), hydroxyapatite (HA), and biphasic ceramics (TCP/HA 80/20)]. Micro-computed tomography (CT) and histology showed that Osteogrow-C induced bone formation on all ceramic scaffolds, with smaller granules resulting in higher bone volume and density, regardless of composition. TCP granules were most resorbed, but residual ceramics persisted in all groups. Based on these findings, Osteogrow-C, containing small granules with different compositions (TCP, HA, TCP/HA 80/20, and TCP/HA 40/60), was further tested in the clinically relevant rabbit PLF model and induced fusion of transverse processes. Importantly, ceramics were more resorbed in the rabbit PLF model, with TCP and TCP/HA 80/20 ceramics showing the highest resorption rate, while HA remained intact. Osteogrow-C containing HA showed increased bone volume; however, biomechanical strength and thicker cortical bone were achieved with TCP and biphasic calcium phosphate (BCP). Finally, in the rat model, bone volume was primarily dependent on granule size, with smaller granules promoting greater bone formation and density. Conversely, in the PLF model, the composition played a more important role-affecting ceramic resorption, bone volume, and biomechanical properties.

Nanotargeted drug delivery systems (nanotargeted DDS) have emerged as promising solutions to improve treatment precision and reduce toxicity. However, achieving efficient delivery from the bloodstream to the tumor site remains challenging due to the complex tumor microenvironment (TME). To address these issues, a novel pH-responsive surface-switching DDS, UiO@CeO₂/IR@(bPEI/HA)-A6, was designed. This system features CeO₂ immobilized on zirconium metal-organic frameworks (UiO-66-NH₂) to create a rough surface, which is then further modified with bPEI and HA-A6 polymers, facilitating its transport in the blood. After loading the photosensitizer IR-820, its photothermal conversion efficiency reached 26.8%, enabling effective photothermal and photodynamic therapy. The HA-A6 polymer enhanced the targeting effect through receptor-mediated recognition, ensuring more drug accumulation at the tumor site; the rough surface constructed by CeO₂ increased cell uptake and enhanced endocytosis in cells. The acidic TME exfoliates the coating, exposing the rough surface of CeO₂, which marked enhances the cellular uptake of DDS, thereby laying a solid foundation for DDS to play an antitumor role. These results indicate that UiO@CeO₂/IR@(bPEI/HA)-A6 has excellent potential in the treatment of multiple myeloma.

Exosomes are nanovesicles secreted by cells to exchange materials and information. Recent studies have revealed that these modified nanovesicles can be powerful tools for the diagnosis and treatment of diseases. However, few studies have reported on the acquisition and application of these functionalized exosomes. Therefore, this study provides a systematic summary of the entire process of isolation, functionalization, modification, and application of enhanced exosomes and recent progress in this field. First, the process of exosome production and principles of disease treatment are elucidated. Thereafter, the methods of exosome isolation are summarized, with a focus on improved technology centered on aptamer technology and new technology represented by microfluidics. Next, the functional modifications of the exosomes are classified and summarized. Finally, new breakthroughs in the diagnostic and therapeutic capabilities of function-enhancing exosomes compared with those of traditional exosomes are summarized, especially in terms of how these exosomes can be used in bioimaging, photothermal therapy, and other means of achieving a quantum leap in detection and therapeutic efficacy. This paper summarizes the latest research findings on engineered exosomes, with a particular focus on emerging technologies such as microfluidics and aptamers that hold significant potential. It provides a thorough analysis of their respective advantages and limitations, aiming to offer actionable insights for the future advancement and more complex applications of exosomes.

This study develops a novel multifunctional nanoplatform, modified polyethylene glycol-bismuth trioxide (mPEG-Bi₂O₃), synthesized via vacuum ball milling followed by ultrasonic liquid-phase exfoliation and surface PEGylation, to enhance the synergistic effects of sonodynamic therapy (SDT) and radiotherapy (RT). Characterization revealed that mPEG-Bi₂O₃ exhibits a thin-layered nanosheet structure (hydrodynamic size: 239.28 ± 4.32 nm; lattice spacing: 0.29 nm) and a zeta potential of -33.64 ± 0.80 mV. Notably, the nanoplatform demonstrated exceptional colloidal stability in physiologically relevant media, maintaining consistent size and surface charge over 7 d in serum-containing medium, which confirms the effectiveness of the PEG coating for biomedical applications. XPS analysis confirmed a mixed Bi³⁺/Bi⁵⁺ oxidation state, and deconvolution of the O 1s spectrum quantified the oxygen vacancy content at 11.02%, confirming a defect-rich structure. Successful PEG grafting was verified by Fourier transform infrared spectroscopy and quantified by thermogravimetric analysis, showing a grafting content of ~13.59 wt %. Under low-intensity focused ultrasound (LIFU), mPEG-Bi₂O₃ significantly enhanced reactive oxygen species generation, leading to a marked reduction in intracellular glutathione levels. In vitro cytotoxicity studies demonstrated favorable selectivity, with lower toxicity toward normal endothelial cells compared to 4T1 cancer cells, and the combination of mPEG-Bi₂O₃ and LIFU induced apoptosis in 4T1 cells. In vivo studies showed that intravenous administration of mPEG-Bi₂O₃ in tumor-bearing mice resulted in peak tumor accumulation at 24 h (0.17 ± 0.03 %ID/g), correlating with a significant 87.82% ± 4.77% reduction in tumor volume after 14 d of treatment when combined with LIFU and RT (10 Gy), superior to dual-modality treatments. Immune profiling indicated enhanced dendritic cell maturation, increased tumor-infiltrating CD8⁺ T cells, and reduced regulatory T cells, demonstrating immune microenvironment remodeling. Collectively, mPEG-Bi₂O₃ presents a surface-engineered strategy for potent SDT-RT synergy with demonstrated biosafety, showing promising potential for solid tumor treatment.

Skin healing often results in scarring or pathological conditions like keloids due to abnormal cell proliferation. These outcomes are attributed to abnormal proliferation or functional defects in skin cells. Hydrogels, mimicking the extracellular matrix, can guide hierarchical cell alignment for improved regeneration. Inspired by egg white's foaming ability, we engineered a bilayer hydrogel dressing: a porous dermis layer via whipped egg white and a dense epidermis layer crosslinked with calcium. The artificial egg white skin (EWS) was tested in in vitro cell culture and in vivo application on mouse wounds. RNA sequencing explored the specific mechanism of EWS on cells. EWS features a multistage macroporous structure mimicking skin's longitudinal mechanical performance. This migration inducive property of egg white facilitates directional migration and allows for the vertical stacking of keratinocytes and fibroblasts. The collaboration of cells enhances expression of positive chemokines and growth factors, shortening inflammation reaction and improving wound healing. Transcriptome sequencing reveals a substantial up-regulation of genes related to cell cycle and metabolism. EWS offers a cost-effective and efficient platform for biomimetic skin dressing and shows potential for other applications in regenerative medicine.

Cisplatin (CDDP) is a widely used chemotherapeutic agent, but its clinical applications are constrained by ototoxic side effects. Currently, few effective strategies exist to prevent or mitigate CDDP-induced ototoxicity. Rutin is known for its cell-protective effects by reducing oxidative stress and inhibiting apoptosis. However, its limited water solubility and inefficient delivery to the inner ear pose substantial challenges. To address this, rutin is encapsulated in liposomes (Lip-Rutin) for nanoscale drug delivery, leveraging its antioxidant properties. Lip-Rutin markedly attenuates CDDP-induced oxidative stress damage and apoptosis, demonstrating a protective effect on OC-1 cells. The efficacy of Lip-Rutin in safeguarding against CDDP-induced ototoxicity is further validated through in vivo studies. Consequently, Lip-Rutin emerges as a promising novel therapeutic agent for combating CDDP-induced ototoxicity.