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Biocompatibility and Toxicity of Magnetic Nanoparticles in Regenerative Medicine

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Regenerative medicine is a pioneering field aimed at restoring and regenerating the function of damaged cells, organs and tissues in order to establish normal function. It demands the cross communication of disciplines to develop effective therapeutic stem cell based therapies. Nanotechnology has been instrumental in the development and translation of basic research to the clinically relevant therapies. In particular, magnetic nanoparticles (MNPs) have been applied to tag, track and activate stem cells offering an effective means of monitoring in vitro and in vivo behaviour. MNPs are comprised of an iron oxide core with a biocompatible biological polymer. Safety is an issue of constant concern and emphasises on the importance of investigating the issue of toxicity. Any indication of toxicity can ultimately limit the therapeutic efficiency of the therapy. Toxicity is highly dependent on the physical, chemical and structural properties of the MNP itself as well as dose and intended use. Few in vitro studies have reported adverse effects of MNP on cells at in vitro in therapeutic doses. However, long term in vivo studies have not been studied as extensively. This review aims to summarise current research in this topic highlighting commonly used toxicity assays to investigate this.
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... Despite the significant biomedical advantages offered by magnetic nanofluids, their nanoparticle toxicity remains a major concern [134][135][136][137][138][139][140]. Bauri et al. [140] found that certain magnetic nanoparticles, such as iron oxide and cobalt ferrite, exhibit considerable toxicity, potentially causing inflammation, ulcer formation, reduced growth rate, altered cell behavior, and decreased viability in cell lines and various model organisms. ...
... They noted that the toxicity of magnetic particles is influenced by factors such as dosage, chemical composition, particle size, structural properties, solubility, surface chemistry, administration method, biodegradability, pharmacokinetics, and biodistribution. Markides et al. [137] also highlighted that magnetic nanoparticles can adversely affect cells at therapeutic doses in vitro, underscoring the need for thorough studies to mitigate both immediate and long-term risks associated with magnetic nanofluids in biological systems. ...
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This chapter provides a comprehensive overview of magnetothermal (MT) and magnetorheological (MR) nanofluids, emphasizing their properties, applications, and safety considerations in engineering and biomedical fields. MT nanofluids, which generate heat under magnetic fields, and MR nanofluids, known for their tunable viscosity and responsiveness, represent significant advancements in thermal management, adaptive systems, and medical treatments. We examine their composition, heat generation mechanisms, and thermal and magnetic properties, supported by computational fluid dynamics and molecular dynamics simulations. Key applications include precision machining, adaptive damping systems, cancer therapy, and advanced prosthetics. Despite their potential, challenges such as biocompatibility, stability, and regulatory compliance remain. The chapter underscores the importance of robust safety protocols and risk assessments to mitigate potential health risks. Future directions include enhancing biocompatibility, improving long-term stability, improving the accuracy of multiscale simulation approach, and expanding the scope of applications. This detailed exploration aims to facilitate future research and development, advancing the practical use of MT and MR nanofluids.
... A primary concern is the detection limit, as current techniques often have low sensitivity, making it difficult to detect biomarkers at low concentrations critical for early diagnosis (Balaban Hanoglu et al., 2023;Su et al., 2020;Farinha et al., 2021). The toxicity of MNPs depends on factors like structural properties, dosage, and chemical composition; while some materials, inert in bulk, become toxic at nanoscale (e.g., gold), metals like cobalt and cadmium are harmful at all scales, whereas titanium and iron oxide are generally safer for cells (Markides et al., 2012). Currently, MNPs are predominantly used in vivo to enhance MRI contrast through improved relaxation times (Yu et al., 2011). ...
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Introduction Magnetic nanoparticles (MNPs), particularly iron oxide nanoparticles (IONPs), are renowned for their superparamagnetic behavior, allowing precise control under external magnetic fields. This characteristic makes them ideal for biomedical applications, including diagnostics and drug delivery. Superparamagnetic IONPs, which exhibit magnetization only in the presence of an external field, can be functionalized with ligands for targeted affinity diagnostics. This study presents a computational model to explore the induced voltage in a search coil when MNPs pass through a simulated blood vessel, aiming to improve non-invasive diagnostic methods for disease detection and monitoring. Methods A finite element model was constructed using COMSOL Multiphysics to simulate the behavior of IONPs within a dynamic blood vessel environment. Governing equations such as Ampère’s law and Faraday’s law of induction were incorporated to simulate the induced voltage in a copper coil as MNPs of various sizes flowed through the vessel. Rheological parameters, including blood viscosity and flow rates, were factored into the model using a non-Newtonian fluid approach. Results The amount of MNPs required for detection varies significantly based on the sensitivity of the detection equipment and the size of the nanoparticles themselves. For highly sensitive devices like a SQUID voltmeter, with a coil sensitivity approximately 10⁻¹² V, very low MNP concentrations—approximately 10⁻⁴ μg/mL—are sufficient for detection, staying well within the safe range. As coil sensitivity decreases, such as with standard voltmeters at 10⁻⁸ V or 10⁻⁶ V, the MNP concentration required for detection rises, approaching or even exceeding potentially toxic levels. Additionally, the physical size of MNPs plays a role; larger nanoparticles (e.g., 50 nm radius) require fewer total particles for detection at the same sensitivity than smaller particles like those with a 2.5 nm radius. For instance, at a coil sensitivity of 10⁻¹⁰ V, a 2.5 nm particle requires approximately 10¹² particles, whereas a 50-nm particle only needs 10⁸. This highlights the importance of optimizing both detection sensitivity and particle size to balance effective detection with safety. Conclusion This computational model demonstrates the feasibility of using superparamagnetic nanoparticles in real-time, non-invasive diagnostic systems.
... Within benchtop settings, the biocompatibility of iron-oxidebased MNPs has been extensively studied and is found to be biologically safe [180]. However, to enable confidence in the translation of these MNP-mediated applications there needs to be further studies into long-term effects in patients in vivo, or those arising from more extensive usage in future therapies. ...
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