Advanced Nanobiomed Research最新文献

This study presents a versatile perfusion bioreactor system designed to evaluate endothelialization on electrospun polycaprolactone (PCL)–gelatin vascular grafts under controlled flow conditions that mimic physiological and pathological shear stress. The bioreactor enables direct assessment of endothelial cell behavior on 3D graft structures, providing a more physiologically relevant platform compared to traditional static cultures. Electrospun PCL–gelatin grafts demonstrate uniform endothelial cell coverage when exposed to physiological shear stress (>10 dyn cm⁻²), with cells displaying alignment in the direction of flow. Under these conditions, endothelial cells upregulate endothelial nitric oxide synthase and platelet endothelial cell adhesion molecule-1, markers associated with vascular homeostasis, anti-inflammatory activity, and enhanced endothelial migration. In contrast, grafts subjected to pathological shear stress (<5 dyn cm⁻²) exhibit increased expression of intercellular adhesion molecule-1, promoting monocyte adhesion and a proinflammatory response. These findings highlight the importance of physiological flow dynamics in regulating endothelial function and demonstrate the value of this bioreactor system as a platform prior to preclinical evaluation of vascular grafts. By providing a more accurate in vitro model, this system may accelerate the development of bioengineered vascular grafts with improved clinical outcomes.

Cancer immunotherapy has emerged as a transformative approach in oncology, leveraging immune activation to combat malignancies. Despite attaining impressive results, some patients’ subpar reactions draw attention to issues, including insufficient drug accumulation, low therapeutic efficacy, and systemic toxicity. Hydrogel-based delivery systems have emerged as promising solutions due to their biocompatibility, customizable drug release profiles, and ability to maintain local drug retention within tumor tissue. The systems provide the simultaneous delivery of various immunomodulators, including checkpoint inhibitors, cellular treatments, and mRNA vaccines, effectively tackling the intricacies of the tumor microenvironment. Strategies that combine immunotherapy with traditional treatments (chemotherapy, radiation) and novel approaches (photodynamic/photothermal therapy) exhibit synergistic results by promoting immune activation and inhibiting tumor growth. This review thoroughly analyzes hydrogel classifications, mechanistic benefits in localized immunotherapy, and recent developments in combination treatment platforms. Significant obstacles in clinical translation, such as material optimization and the navigation of biological barriers, are examined, while suggesting future pathways through advanced material engineering and precise delivery methods. As hydrogel technology advances with innovative biomaterials and combinatorial strategies, it possesses considerable promise to transform tumor immunotherapy by improving treatment accuracy and reducing off-target effects.

Peripheral nerve injuries frequently result in long-term functional disability and sensory loss due to the lack of appropriate treatment options. Autologous nerve transplantation is currently the gold standard for repairing damaged nerves, but the increased risk of neuroma formation is the most significant issue with this approach. Moreover, the lack of effective treatment methods that allow for simple and clinically significant neural-tissue electrical stimulation has also restricted full functional nerve recovery. To circumvent these limitations, this study devises an electrospun nanofiber-based piezoelectric and conductive nerve conduit (PCNC) that can self-generate electrical stimulations analogous to neural tissues. This work also focuses on designing a low-cost, customizable 3D printed bioreactor to deliver controlled dynamic compressive loading on cell-cultured piezoelectric nanocomposite constructs. By using a custom-designed mechano-stimulator in conjunction with PCNC, the invitro biocompatibility and neuronal differentiation of the PC12 cells are investigated. The results evidence the expression of increased neurogenic differentiation markers from the stimulated PCNC group compared to the unstimulated PCNC control group. When wrapped around a damaged nerve and remotely activated by dynamic mechanical stimulation, this PCNC can give in situ topographical and electrical cues for optimal nerve regeneration due to its unique structure, composition, piezoelectric, and conducting capabilities.

Mesenchymal stem cell (MSC)-derived exosomes (MSC-exosomes) are emerging as promising cell-free therapeutic agents that address many challenges associated with traditional cell-based therapies. However, conventional methods for isolating MSC-exosomes using 2D culture systems are often limited in their efficiency, posing challenges to large-scale production. This study introduces a novel approach to boost MSC-exosome production by promoting cell–cell and cell–extracellular matrix (ECM) interactions. Specifically, ECM-integrated MSC spheroid bioprinting technology is employed to optimize exosome secretion, analyzing the effects of spheroid size and ECM composition on exosome production. It is demonstrated that smaller spheroids constructed using MSCs exhibit an enhanced production of exosomes. Additionally, incorporating ECM components, such as fibrin, Matrigel, and collagen, particularly at higher concentrations, further boosts exosome production. Among these, MSC spheroids with a 150 μm diameter and 0.6% w/v collagen integration demonstrate the highest exosome secretion, achieving an 18.4-fold increase compared to traditional 2D culture systems. Furthermore, exosomes derived from ECM-enhanced MSC spheroids exhibit strong efficacy in an in vitro scratch wound assay, underscoring their therapeutic potential. Thus, the newly developed ECM-incorporated spheroid bioprinting technology offers a highly effective strategy for scaling up MSC-exosome production, paving the way for exosome-based therapeutic applications.

Inflammatory bowel disease (IBD) is a chronic disorder characterized by intestinal barrier dysfunction, excessive immune activation, and oxidative stress. Current treatment options, such as 5-aminosalicylic acid (5-ASA), exhibit limited therapeutic efficacy due to poor bioavailability and inability to restore intestinal homeostasis. Herein, a novel nanomedicine that can be orally administered, low-molecular-weight chitosan-conjugated rosmarinic acid nanoparticles (LMWC-RANPs), designed to enhance IBD treatment through its mucoadhesive, antioxidant, and immunomodulatory properties, are introduced. LMWC-RANPs exhibit strong mucoadhesion, leading to prolonged retention in the inflamed gastrointestinal tract and efficient ROS scavenging. In a DSS-induced mouse model of colitis, LMWC-RANPs significantly alleviate disease symptoms by reducing body weight loss, preserving colon length, and restoring intestinal barrier integrity. Additionally, LMWC-RANPs effectively modulate the mucosal immune response by promoting macrophage polarization from pro-inflammatory (M1) to anti-inflammatory (M2) phenotypes and reducing Th17 cell populations while enhancing regulatory T cell (Treg) frequencies. Furthermore, oral administration of LMWC-RANPs exhibits no observable systemic toxicity in healthy mice, as confirmed by hematological and histopathological analyses. Collectively, these findings demonstrate the potential of LMWC-RANPs as a safe and effective therapeutic for inflammatory bowel disease, with broader implications for other gut-associated inflammatory diseases.

Although the field of gene delivery has made tremendous progress, many obstacles remain to achieve safe, targeted, and controlled delivery and release of nucleic acids. The effective delivery of these therapeutics requires the precise control of physicochemical and biochemical processes regulating a broad range of events, from initial complexation and stabilization in biological fluids, to the crossing of endothelial barriers, internalization, and cytosolic/nuclear release. Polymer brush-functionalized nanoparticles are well suited to control physicochemical parameters that regulate these processes, including the chemical composition of their shell; its grafting density and thickness; as well as the size, shape, and physical properties of its core. In addition, polymer brushes can be designed to display more complex architectures (blocks and mixed brushes), providing further control of the delivery vehicle physicochemistry, size, and hierarchical structure. Here, this study discusses how gene delivery systems can be uniquely engineered, tailoring the physicochemistry of polymer brush-functionalized nanoparticles. In addition, it reviews the impact of brush design on the formation of protein coronas, associated with in vitro transfection, blood circulation, or cytosolic entry. Finally, it discusses how polymer brush engineering enables the design of nanomaterials for theranostics applications.

Breakthrough infections in vaccinated population and continuous emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants make it imperative to develop more efficacious medical countermeasures. Previously, an anti-SARS-CoV-2 nanobody, Nanosota-3A, that neutralizes the infection of live Omicron BA.1 with picomolar potency, is identified. Herein, Nanosota-3A is fused with the crystallizable fragment (Fc) domain of human IgG1 that contains M252Y/S254T/T256E (YTE) substitutions, named Nanosota-3A-Fc-YTE. Compared to Nanosota-3A-Fc, Nanosota-3A-Fc-YTE exhibits identical binding to the SARS-CoV-2 spike protein yet displays eightfold higher binding affinity for human neonatal Fc receptor (hFcRn) at pH 6.0. In hFcRn transgenic mice, the half-life of Nanosota-3A-Fc and Nanosota-3A-Fc-YTE is 5.1 days and 24.8 days, respectively. The mice are challenged with intranasal exposure of Omicron B.1.1.529 virus 55 days after a single dose of Nanosota-3A fusions (20 mg kg⁻¹) is administered. Compared to the untreated controls, the lung viral titers in mice receiving Nanosota-3A-Fc-YTE are reduced by 104.7-fold (p = 0.007) with 50% of the mice free of detectable virus. By contrast, Nanosota-3A-Fc-treated mice show only 3.5-fold reduction in the viral titers (p = 0.41). The durable protection conferred by a single dose of Nanosota-3A-Fc-YTE administered nearly 2 months prior to the virus exposure demonstrates the promise of long-circulating nanobodies as powerful prophylactics against SARS-CoV-2.

Antimicrobial resistance (AMR) poses a significant challenge in wound management, particularly in ischemic and chronic wounds, which are prone to infection and where traditional treatments often fall short. In response to this need, the antibacterial activity of polycaprolactone (PCL) films, composited with sodium perborate and sodium percarbonate to provide controlled release of oxygen and reactive oxygen species, is compared in vitro and in vivo. Sustained antimicrobial action against both Gram-positive and Gram-negative bacteria is measured in vitro that allowed lower quantities to be used compared with the borate and carbonate counterparts sodium borate and carbonate. This effect is also observed in vivo, such that perborate formulations are effective at wound treatment using one-tenth the borate concentration required in sodium borate formulations. Overall, sodium perborate-loaded films significantly accelerate wound closure, reduce bacterial load, and enhance early-phase wound healing, outperforming borate equivalent counterparts at equivalent loading levels. In addition to effectively inhibiting bacterial growth, these composites prevent biofilm formation in vitro. These findings suggest that perborate-loaded polymeric films could be a powerful tool in advanced wound care, offering both potent antimicrobial effects and promotion of wound healing in complex clinical settings.

Platelets play a crucial role in tumor development through a bidirectional interaction with cancer cells. On one hand, platelets promote tumor proliferation, metastasis, and immune evasion; on the other, tumors can activate platelets, creating a feedback loop that accelerates disease progression. Disrupting this interaction by targeting platelets has emerged as a promising strategy to control tumor growth and dissemination. However, traditional antiplatelet drugs often lack tumor specificity, limiting their therapeutic efficacy and increasing the risk of adverse effects such as bleeding. To overcome these limitations, researchers have turned to nanotechnology to design platelet-modified nanoparticles that enhance tumor targeting and improve treatment precision. This review summarizes recent advances in the development of these nanoparticles, including those aimed at modulating platelet-tumor interactions, directly treating tumors, or improving radiotherapy outcomes. The distinct advantages of platelet-modified nanoparticles are also discussed, such as enhanced drug delivery, minimized off-target effects, and superior biocompatibility. Finally, their potential clinical applications and implications for cancer therapy is explored, highlighting how these innovations could transform the treatment landscape for malignant tumors. This review underscores the significance of platelet-targeting strategies in advancing cancer nanomedicine and addresses current challenges in the field.

Intervertebral disc degeneration (IVDD), a major cause of low back pain, poses significant global health and socioeconomic challenges. Current therapies have limited effectiveness in reversing degeneration, which underscores the need for advanced treatment strategies. Exosomes, which are nanoscale extracellular vesicles, have emerged as promising therapeutic agents for IVDD due to their unique biological properties. They exert their effects through multiple mechanisms, such as regulating the extracellular matrix, promoting cell proliferation, and exerting anti-inflammatory effects. This review summarizes recent advances in exosome-based therapies for IVDD. It encompasses their mechanisms, cell sources, engineering technologies, and progress in clinical translation. Additionally, the challenges and opportunities related to their future clinical application are discussed, and their potential to revolutionize the treatment of IVDD is highlighted.