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Purpose: Bioprinting is an additive manufacturing technology analogous to 3D printing. Instead of plastic or resin, cell-laden hydrogels are used to produce a construct of the intended biological structure. Over time, cells transform this construct into a functioning tissue or organ. The process of printing followed by tissue maturation is referred to as 4D bioprinting. The fourth dimension is temporal. Failure to provide living cells with sufficient amounts of oxygen at any point along the developmental timeline may jeopardize the bioprinting goals. Even transient hypoxia may alter cells' differentiation and proliferation or trigger apoptosis. Electron paramagnetic resonance (EPR) imaging modality is proposed to permit 4D monitoring of oxygen within bioprinted structures.
Procedures: Lithium octa-n-butoxy-phthalocyanine (LiNc-BuO) probes have been introduced into gelatin methacrylate (GelMA) bioink. GelMA is a cross-linkable hydrogel, and LiNc-BuO is an oxygen-sensitive compound that permits longitudinal oximetric measurements. The effects of the oxygen probe on printability have been evaluated. A digital light processing (DLP) bioprinter was built in the laboratory. Bioprinting protocols have been developed that consider the optical properties of the GelMA/LiNc-BuO composites. Acellular and cell-laden constructs have been printed and imaged. The post-printing effect of residual photoinitiator on oxygen depletion has been investigated.
Results: Models have been successfully printed using a lab-built bioprinter. Rapid scan EPR images reflective of the expected oxygen concentration levels have been acquired. An unreported problem of oxygen depletion in bioprinted constructs by the residual photoinitiator has been documented. EPR imaging is proposed as a control method for its removal. The oxygen consumption rates by HEK293T cells within a bioprinted cylinder have been imaged and quantified.
Conclusions: The feasibility of the cointegration of 4D EPR imaging and 4D bioprinting has been demonstrated. The proof-of-concept experiments, which were conducted using oxygen probes loaded into GelMA, lay the foundation for a broad range of applications, such as bioprinting with many types of bioinks loaded with diverse varieties of molecular spin probes.
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http://dx.doi.org/10.1007/s11307-023-01871-0 | DOI Listing |
Adv Mater
September 2025
Department of Diagnostic Radiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 119074, Singapore.
Nanomedicine has shown remarkable promise in advancing tumor imaging and therapy through its ability to achieve targeted delivery, precision imaging, and therapeutic efficacy. However, translating these preclinical successes into clinical practice remains fraught with challenges, including inconsistent tumor targeting, off-target organ accumulation, and a lack of comprehensive understanding of in vivo behavior of nanomedicines. In this perspective, the current state of nanomedicine research is critically analyzed, emphasizing the translational bottlenecks and offering a forward-looking view on potential solutions.
View Article and Find Full Text PDFBiomater Sci
September 2025
Britton Chance Center for Biomedical Photonics at Wuhan National Laboratory for Optoelectronics Hubei Bioinformatics & Molecular Imaging Key Laboratory, Department of Biomedical Engineering, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, Hubei,
Cuproptosis is a copper-dependent programmed cell death triggered by mitochondrial dysfunction, which offers significant anti-tumor potential but requires tumor-specific copper delivery to avoid systemic toxicity. Here, we developed a synergistic nanoplatform (CuO@SiO-Ce6, CSC) integrating cuproptosis induction with photodynamic therapy (PDT). A cuprous oxide (CuO) core was encapsulated in silicon dioxide and covalently linked to the photosensitizer Ce6.
View Article and Find Full Text PDFDiscov Imaging
August 2025
Cardiovascular Pulmonary Research Laboratories and Pediatric Critical Care Medicine, University of Colorado Anschutz Medical Campus, 12700 E. 19 Ave., Aurora, CO 80045 USA.
Unlabelled: Superoxide (O ) production in an acute lung injury (ALI) murine model was detected by electron paramagnetic resonance (EPR) spectroscopy and imaging. Lung injury was induced in wild-type (WT) mice and transgenic (Tg) mice with lung-specific EC-SOD overexpression by lipopolysaccharide (LPS) administered intraperitoneally (IP) at a dose of 10 mg/kg. At 24 h after LPS treatment, mice were treated intraperitoneally and subcutaneously with the cyclic hydroxylamine probe, CMH, for superoxide measurements in the blood, or via intratracheal delivery (IT) with the cyclic hydroxylamine probes, CPH or DCP-AM-H, for lung cellular and mitochondrial superoxide detection.
View Article and Find Full Text PDFMol Cancer
September 2025
Department of Thoracic Surgery, The First Hospital of China Medical University, No. 155 Nanjingbei Street, Heping District, Shenyang, 110001, Liaoning, China.
Iron oxide nanoparticles (IONPs) have transitioned from conventional magnetic resonance imaging (MRI) contrast agents into structurally programmable combined imaging/treatment tools, leveraging their superparamagnetism, catalytic activity, and surface engineering versatility to achieve spatiotemporal control over drug delivery and immune modulation. Advances in nanofabrication now yield size-optimized aggregates with enhanced tumor accumulation through the enhanced permeability and retention (EPR) effect, while clinically approved formulations like ferumoxytol demonstrate intrinsic immunomodulatory functionality, positioning IONPs as pivotal tools for precision oncology. Conversely, cancer immunotherapy remains limited by the immunosuppressive tumor microenvironment (TME), where cellular suppression via M2-polarized macrophages and regulatory T cells (Tregs) synergizes with physical exclusion from dense extracellular matrices and metabolic sabotage through lactate-driven acidosis.
View Article and Find Full Text PDFIn Vivo
August 2025
Institute for Quantum Medical Science, National Institutes for Quantum Science and Technology (QST), Chiba, Japan.
Background/aim: Redox imaging is one of the fastest growing areas in diagnostics of pathologies accompanied by redox imbalance. We describe a multi-spin redox sensor (RS) and its application for redox imaging in mice using electron paramagnetic resonance (EPR) spectroscopy.
Materials And Methods: The probe is composed of a quantum dot functionalized with a cyclodextrin shell, conjugated with nitroxide residues (TEMPO) and triphenylphosphonium to achieve intracellular delivery.