Advanced Nanobiomed Research最新文献

In emergency situations involving the loss of hard tissues, immediate treatment is crucial. While 3D-printed scaffolds offer structural support for damaged tissue, the processes of tissue integration and blood vessel formation remain challenging. To address these issues, stem cell therapies show promise; however, current treatments lack efficacy in urgent situations due to limited transplantation methods available for the defect. In this study, a 3D-printed poly(methyl methacrylate) (PMMA) scaffold loaded with high-density stem cells from the apical papilla (SCAP) using an injectable hydrogel composed of carboxymethyl chitosan (CMCTS) and oxidized hyaluronic acid (oHA) is developed. The SCAPs are directly incorporated in CMCTS/oHA hydrogel through self-crosslinking and subsequently injected in the 3D-printed PMMA scaffold. The hydrogel-laden scaffold exhibits excellent mechanical properties. In vitro analysis shows that the hydrogel is fully degraded, leading to the formation of 3D tissue both within and outside the scaffold. When implanted in mice without prior in vitro culture, the transplants are fully fused after 3 weeks, achieving strong tissue integration. In addition, mature blood vessels are histologically confirmed. Therefore, this research has potential applications in musculoskeletal tissue engineering, where immediate treatment is required, making these results suitable for volumetric tissue regeneration through stem cell transplantation.

Adipose tissue represents an active metabolic and endocrine organ that influences (patho-)physiological processes in metabolism, immune response, or cancer progression. Given the close relationship between morphology and functionality, adipose models that recapitulate the phenotype of mature adipocytes embedded in a tissue-specific matrix are essential for studies on adipose tissue biology. In order to mimic the high cell density and 3D architecture of the native tissue, scaffolds made of ultrathin fibers produced with melt electrowriting (MEW) technology are combined with adipose-derived stromal cell (ASC) spheroids. Fabricated constructs develop an adipose phenotype, demonstrated by storage of triglycerides, expression of adipogenic marker genes, and the development of a tissue-specific extracellular matrix. Upon oleic acid supplementation, differentiated adipocytes significantly increase lipid storage. Tissue functionality is demonstrated by analysis of secreted adipokines and β-adrenergic stimulation of lipolysis. Long-term culture (10 weeks) favors adipocyte maturation to lipid droplet sizes close to those in native tissue, while tissue stability and functionality are unaffected. This hybrid tissue engineering approach, using spheroids as building blocks in tailored MEW scaffolds, provides an adipose model that closely mimics structural and functional characteristics of fat tissue and is therefore an excellent tool for studies on the function and (patho-)physiology of adipose tissue.

Anticancer cell therapies have remarkable clinical potential yet fail to reach the clinic due to poor delivery. 3D bioprinting (3DBP) can be leveraged for generating cell therapy delivery devices, where the biomaterial system acts as a protective matrix to stabilize cells after implantation. Continuous liquid interface production (CLIP), an additive manufacturing technology, has several unique features that make it a suitable platform for 3DBP of cell-laden scaffolds. However, the feasibility CLIP bioprinting and efficacy of CLIP-bioprinted cell/matrix therapies have not yet been explored. In this work, we demonstrate the utility of CLIP for cell therapy 3DBP with a simple gelatin methacrylate-based resin and anticancer drug-secreting fibroblasts as a model therapy against recurrent glioblastoma. We demonstrate that CLIP enables rapid, consistent production of cell-laden scaffolds, and cells maintain their viability and tumor-killing efficacy in vitro post-printing. Importantly, we proved that bioprinted cells survive longer in vivo than directly injected cells, and that this effect may correspond to better survival outcomes in a mouse model of glioblastoma resection. This study is the first to utilize CLIP for 3DBP of composite devices containing anticancer cell therapies, providing a crucial foundation for developing highly refined cell therapy delivery devices in the future.

Glioma, particularly glioblastoma multiforme, is still one of the most aggressive and chemoresistant forms of brain cancer, in large part attributed to the hindrance of the blood–brain barrier (BBB), tumor heterogeneity, and complicated tumor microenvironment. Recent progress in nanobiotechnology has provided with opportunities to achieve targeted glioma therapy through the delivery of drugs selectively to the tumor through the BBB, thereby enhancing therapeutic efficacy and reducing side effects. In this review, the use of different nanocarrier systems, including lipid nanoparticles, polymeric nanoparticles, and magnetic nanoparticles, for the treatment of glioma, is summarized. These systems can achieve increased drug accumulation in the tumor site, controlled release of the drug, and synergistic influence with immunotherapy, chemotherapy, or radiotherapy. A detailed review of state-of-the-art emerging approaches, including RNA-based nanoparticles, surface-modified nanocarriers, and nanorobots that hold great potential in personalized and precision glioma treatments, is also provided. In addition, the review covers major obstacles to clinical transformation, i.e., nanotoxicity, controlling sustained drug release, and production difficulties. Overcoming these challenges, nanobiotechnology may lead to a paradigm shift in the treatment of glioma and clinical services for patients.

Cancer cells undergo significant metabolic reprogramming to meet their increased bioenergetic and biosynthetic needs, supporting rapid proliferation and survival. Key metabolic pathways, including those involved in glucose, lactate, amino acid, lipid, and nucleotide metabolism, are altered to facilitate cancer development, maintenance, and metastasis. Therefore, targeting cancer metabolism emerges as a promising therapeutic strategy. However, because of their short half-life, limited bioavailability, and inadequate specificity in metabolic regulation, these agents often result in unsatisfactory therapeutic outcomes. Recently, innovative nanomedicines that target metabolic processes have gained attention as a promising cancer therapy strategy, potentially helping to overcome the limitations of individual therapies and enhance treatment efficacy. This review provides an overview of tumor metabolic characteristics and explores recent progress in developing functional nanomedicines targeting tumor metabolism for cancer treatment. Finally, this review discusses the challenges and prospects for advancing nanotechnology-driven metabolic therapies.

Silica microparticles and nanoparticles (SiNPs) have been studied as vehicles for vaccines. They are safe, biodegradable, and biocompatible and can be used as carriers and adjuvants. These particles are applied in both noncommunicable and infectious disease research for new treatments to address priority health challenges. Several reviews report the use of SiNPs in cancer vaccines. The aim of this review is to provide a detailed summary of the use of SiNPs in vaccines against infectious diseases over the last 12 years. The use of silica particles in classical vaccines based on recombinant subunits or whole proteins and in recent vaccines based on nucleic acids, such as DNA and mRNA, is discussed. Additionally, the intrinsic properties of the particles that induce an immune response and their use as adjuvants are outlined. Easy modification of the surface of silica particles facilitates their interaction with different molecules, such as DNA or RNA, making these particles good vehicles. Additionally, preclinical studies on vaccines against human infections and animal diseases are discussed.

Endometriosis (EM) is a gynecological disease where endometrial tissue grows outside the uterus. Current diagnostic methods are mainly through surgical visualization with histological verification; there's a need for noninvasive approaches. Herein, it is reported that photoacoustic imaging (PAI) can be a noninvasive imaging modality for deep-seated EM by employing FITC-tagged, silica-coated gold nanorods (AuNR@Si(F)-PEG) as the contrast agent. When the nanoparticles are injected intravenously into mice with EM, the strong PA signals from AuNRs are detected from the EM tissues by particle accumulation in the EM lesions through the enhanced permeability and retention effect. Additionally, due to the presence of FITC, the nanoparticles (NPs) facilitate easy identification and isolation of endometriosis tissue under a fluorescence dissection microscope. Owing to the high photothermal ablation property of AuNRs, the NPs can be used for laser-induced thermal ablation therapeutics to shrink the endometriosis lesions, validated by imaging, pro-apoptotic marker cleaved caspase-3, and H&E staining. This technique provides new avenues for studying endometriosis development, progression, and the related treatment modalities.

In this study, the potential of maghemite (γ-Fe₂O₃) nanoparticles (MNPs) functionalized with doxorubicin (DOX) is explored for chemo-magneto-photothermal therapy in cancer treatment. MNPs are functionalized through electrostatic interactions or disulfide bonds, achieving high drug-loading efficiencies. The trimodal approach combines magnetic hyperthermia (MHT), photothermal therapy (PTT) and local chemotherapy, utilizing low and clinically relevant doses. Thermal treatments induced controlled temperature increases, triggering pH-sensitive DOX release in the acidic environments typical of tumors. Efficient uptake of DOX-loaded MNPs is observed, and their structural integrity is confirmed using advanced synchrotron spectroscopic techniques. Cytotoxicity assays show that MHT and PTT together enhanced therapeutic efficacy compared to free DOX, while minimizing toxicity to healthy cells. This study demonstrates that combining thermal therapies with controlled drug release provides a promising strategy for improving cancer treatment outcomes. The findings highlight the potential clinical application of multifunctional nanoparticle systems for targeted, low-toxicity cancer therapies, advancing the path toward more effective and accessible treatments.

Cardiovascular diseases remain a leading cause of global mortality, necessitating advancements in vascular graft technologies, particularly for small-diameter grafts. This study presents a novel biomimetic approach to address these issues by combining polyvinyl alcohol methacrylate (PVA-MA)-based hydrogels with melt-electrowritten (MEW) scaffolds, creating an off-the-shelf, customizable platform for vascular graft applications where the hydrogels offer potential as extracellular matrix for cell attachment and growth while the MEW scaffolds provide mechanical reinforcement. Here, the PVA-MA hydrogel is biofunctionalized with heparin-methacrylate (Hep-MA) and gelatin-methacrylate (Gel-MA) for enhanced hemocompatibility and endothelialization, respectively. Four hydrogel formulations, PVA-MA (P10), PVA-MA with 5% (wt/v) Gel-MA (P10-G5), PVA-MA with 0.5% (wt/v) Hep-MA (P10-H0.5), and their combination (P10-G5-H0.5), are fabricated and characterized. Acute biological responses relevant to vascular graft performance are evaluated in this study. Gelatin and heparin both remain biofunctional post the methacrylation and copolymerization processes while the presence of MEW scaffolds does not affect the biological interactions. P10-G5-H0.5 exhibits prolonged clotting times, minimal thrombus formation, and enhanced endothelial cell adhesion and proliferation. The tubular scaffolds support confluent endothelial layers in 3D culture, showcasing their potential for vascular graft applications. These findings demonstrate the promise of combining biological functionality with mechanical reinforcement to develop next-generation off-the-shelf vascular grafts.

A magnetically gated, enzymatically driven DNA release platform based on sustainable pyrolyzed walnut shell-derived carbon electrodes is reported. Upon glucose addition under aerobic conditions, biocatalytic oxygen reduction at the cathode induces a local pH increase, resulting in electrostatic repulsion of negatively charged 5(6)-carboxyfluorescein-labeled DNA (FAM-labeled DNA). Electrochemical analysis reveals an oxygen reduction reaction (ORR) onset potential of +0.576 ± 0.003 V vs. Ag/AgCl and a maximum current of −8.2 ± 0.4 μA. Electrochemical impedance spectroscopy (EIS) confirms a post-ORR increase in interfacial resistance from 6.2 ± 0.5 to 11.1 ± 0.9 kΩ. DNA release reaches 97% after 400 min, corresponding to a surface density of 22 ± 4 nmol cm⁻². A competing enzymatic gate, composed of co-immobilized glucose oxidase and catalase (GOx–CAT) on magnetic nanoparticles (MNPs), enables remote suppression of electron flow and DNA release upon application of a 0.3 T magnetic field. Under “OFF” conditions, DNA release is reduced to 1%, and anodic current decreases by 60%. The system exhibits excellent reversibility over four ON–OFF cycles with minimal performance degradation. This bioelectronic platform represents a self-powered, reversible strategy for stimuli-responsive drug release.