Advanced Nanobiomed Research最新文献

Mechanoadaptive Responses

In this cover image, the newly found mechanoadaptive response of neutrophils adhesion and the membrane tether coalescence MI-SIM super-resolution images under abrupt flow acceleration are emphasized and represented. More details can be found in the Research Article by Lining Arnold Ju and co-workers (DOI: 10.1002/anbr.202500113).

Craniofacial Tissue Engineering

This research illustrates an innovative strategy for immediate tissue repair using a 3D-printed scaffold infused with primary stem cells-laden hydrogels. Without prior culture, the construct promotes rapid tissue integration and vascularization upon implantation in vivo. This approach represents a promising advancement for emergency craniofacial tissue regeneration, enabling volumetric tissue healing through direct and effective stem cell transplantation. More details can be found in the Research Article by Sangjin Lee and co-workers (DOI: 10.1002/anbr.202500006).

Neutrophils navigating the vasculature encounter regions of abrupt flow acceleration that challenge their adhesive capacity. Here, a previously uncharacterized mechanoadaptive response that enables neutrophils to maintain adhesion under these challenging conditions is revealed. Using microfluidic systems to precisely control flow dynamics, it is demonstrated that neutrophils respond differently to steady versus accelerating flow (delta shear) conditions. While steady-increasing flow induces formation of multiple discrete tethers, abrupt acceleration triggers their coalescence into thicker, mechanically robust structures that significantly enhance adhesion stability. Through Machine Intelligent Structured Illumination Microscopy with exceptional spatiotemporal resolution, the nanoscale dynamics of this coalescence process is characterized, revealing that despite extensive membrane remodeling, the original anchor points of adhesion molecules remain spatially fixed. Dual-color spinning total internal reflection fluorescence imaging shows targeted accumulation of F-actin at the cell tongue, providing critical mechanical support. Differential effects of actin-disrupting agents confirm that tether coalescence depends on intact cytoskeletal structures rather than active polymerization. This membrane adaptation represents a sophisticated strategy enabling neutrophils to withstand high detachment forces in disturbed flow environments characteristic of vascular bifurcations, stenoses, and device-associated thromboinflammation. These findings advance understanding of neutrophil mechanobiology and may inform therapeutic strategies targeting pathological neutrophil adhesion without compromising essential immune functions.

A magnetically actuated DNA release platform employing sustainable walnut shell–derived electrodes enables precise ON/OFF switching of DNA release through magnetic–enzymatic filter beads, offering a controllable and reusable system for bioelectronic and sensing applications. More details can be found in the Research Article by Paolo Bollella, Luisa Torsi, and co-workers (DOI: 10.1002/anbr.202500131).

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.

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.

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.

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.