Advanced Nanobiomed Research最新文献

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.

The rapid advancement in nanotechnology over the past three decades has accelerated the development of novel and more potent cancer treatments. In particular, this has led to the development of an increasing number of novel carrier systems for drug delivery, among which Pickering emulsions are a strong contender. This article reviews the development, characterization, and therapeutic efficacy of Pickering emulsion nanocarriers designed specifically for cancer treatment. This approach offers significant benefits for overcoming many of the challenges experienced in conventional drug delivery systems for cancer therapy. The mechanisms of drug release, targeting strategies, and the stability of Pickering emulsions under physiological conditions are examined, along with an evaluation of their therapeutic potential and biocompatibility of these nanocarriers in various cancer models with in vitro and in vivo studies. The ability of Pickering emulsions to improve therapeutic efficacy through encapsulation and protection of hydrophobic drugs is also highlighted, resulting in targeted drug release at the tumor site and minimal side effects. Future development of the nanocarrier systems must address the challenges of achieving large-scale production, regulatory approval, and translational application. If successfully addressed, it will pave the way for making personalized delivery of therapeutics for cancer treatment a reality.

Pathological scarring imposes a substantial global healthcare burden, affecting over 100 million individuals annually with costs exceeding $20 billion. Current therapies yield suboptimal outcomes due to limited efficacy and recurrence. Hydrogel-based wound dressings have emerged as transformative platforms due to their tunable physicochemical properties, bioactivity, and ability to modulate the wound microenvironment. This review uniquely integrates scar biology with hydrogel-based therapeutic strategies. A phase-specific framework that correlates hydrogel functions is provided with key scar-influencing events, including inflammation regulation, fibroblast reprograming, extracellular matrix remodeling, and skin appendage regeneration. Moreover, cutting-edge innovations are highlighted such as stimuli-responsive hydrogels (pH/temperature/light), nanocomposite systems, and 3D-printed scaffolds that enable spatiotemporal control of drug release and dynamic microenvironment modulation. Furthermore, unresolved clinical translation barriers are critically addressed, including scalability, standardization, biocompatibility, and immune response variability, proposing interdisciplinary solutions. By synthesizing recent advances and persistent limitations, this work provides a translational roadmap for developing next-generation hydrogels to bridge the gap between benchtop innovation and clinical scar-free tissue regeneration.

Glioblastoma multiforme (GBM), the most common and highly aggressive primary malignant central nervous system tumor, has seen minimal improvement in its median survival of <24 months. This study investigates the codelivery of copper oxide nanoparticles (CuO NPs) and acriflavine (ACF), a hypoxia-inducible factor-inhibiting drug, to provide synergistic dual reactions in order to effectively kill tumor-initiating cells and to target multiple processes implicated in GBM progression. The two anticancer agents are embedded in polymeric core-sheath nanofibers formed by coaxial electrospinning. Transmission electron microscopy and dispersive X-ray spectroscopy mapping are used to confirm the uniform distribution of CuO NPs in the fiber core. Fourier transform infrared spectroscopy and thermogravimetric analysis results suggest that drug-core polymer interactions mainly occur through weak bonding with the solvent surrounding the core-polymer chains, leading to a relatively faster drug release. Cytotoxicity of combinations of drugs is evaluated in vitro against the GL261-LUC cell line, showing a very strong synergistic effect. Dose-effect-based model presents the average combination index of ≈0.48 and dose reduction index of 19.6 for ACF and 2.6 for CuO NPs. A 3D GBM spheroid model is utilized to better mimic the tumor microenvironment, including cell heterogeneity and hypoxic conditions.

Semiconducting polymer nanoparticles (SPNs) hold great promise as fluorescent nanoparticles with many advantageous optical and biological properties. However, their potential for optical imaging in clinical applications is currently restricted by limited tissue penetration, compared to the depth offered by magnetic resonance imaging (MRI). Multimodal SPN-based contrast agents that integrate different, complementary imaging modalities into one platform allow the strengths to be combined and the weaknesses mitigated. This study presents an accessible route to modular, well-defined, and versatile dual modality SPNs composed of red-emitting SPNs functionalized with novel gadolinium-based contrast agents (GBCAs). The Gd unit is attached to the surface of the SPN using a rigid linker, providing a robust attachment point as well as enhancing the MRI performance. Preliminary in vitro studies show that the SPNs are nontoxic across all concentrations tested and are readily taken up by cells, illustrating their potential as imaging probes. Anchoring the GBCA unit to the surface of the SPN yields a dramatic increase in the relaxivity compared to the unattached contrast agent unit. The dual modality probe shows a fourfold relaxivity enhancement over the clinical standard, Dotarem, at clinical field strengths, making this dual modality platform a promising design for combined optical and MR imaging.

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).

The prompt identification of pancreatic cancer symptoms is an ongoing clinical challenge, often leading to late diagnosis and poor prognosis. Tumor “hijacking” of the pancreatic stromal structure limits the uptake of systemic chemotherapeutics. Localized drug delivery systems (DDS) using endoluminal techniques are widely utilized, with positive early results for improved control over tumor growth. There is a need for technologies that integrate endoluminal resources and intelligent material systems to better control the spatiotemporal delivery of chemotherapeutics. The ultrasound (US)-triggered localized release of therapeutics through the design of solvent traceless drug-loaded vinylbenzyl-functionalized gelatin (gel4vbc) nanoparticles (NPs) integrated with an electrospun fabric is demonstrated. Albumin-loaded NPs encapsulated into a poly(vinyl alcohol) (PVA) coating of a poly(ε-caprolactone) fabric evidence tunable triggered NP delivery controlled by regulating PVA concentration (0–1 wt%) and US intensity (0–3 W cm⁻²). The fixation of the NP-coated fabric to a magnetic tentacle robot (MTR) enables the automated manipulation into a phantom pancreatic duct before the US-triggered release of NP-loaded albumin and MTR retraction. Albumin release is controlled by varying the surface area of the NP-loaded MTR-coating fabric. Herein a novel DDS capable of facile integration into soft robotics and US-triggered delivery of therapeutic-loaded NPs is designed.

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.