Magnetic nanoparticles have attracted significant attention in various disciplines, including engineering and medicine. Microfluidic chips and lab-on-a-chip devices, with precise control over small volumes of fluids and tiny particles, are appropriate tools for the synthesis, manipulation, and evaluation of nanoparticles. Moreover, the controllability and automation offered by the microfluidic chips in combination with the unique capabilities of the magnetic nanoparticles and their ability to be remotely controlled and detected, have recently provided tremendous advances in biotechnology. In particular, microfluidic chips with magnetic nanoparticles serve as sensitive, high throughput, and portable devices for contactless detecting and manipulating DNAs, RNAs, living cells, and viruses. In this work, we review recent fundamental advances in the field with a focus on biomedical applications. First, we study novel microfluidic-based methods in synthesizing magnetic nanoparticles as well as microparticles encapsulating them. We review both continues-flow and droplet-based microreactors, including the ones based on the cross-flow, co-flow, and flow-focusing methods. Then, we investigate the microfluidic-based methods for manipulating tiny magnetic particles. These manipulation techniques include the ones based on external magnets, embedded micro-coils, and magnetic thin films. Finally, we review techniques invented for the detection and magnetic measurement of magnetic nanoparticles and magnetically labeled bioparticles. We include the advances in anisotropic magnetoresistive, giant magnetoresistive, tunneling magnetoresistive, and magnetorelaxometry sensors. Overall, this review covers a wide range of the field uniquely and provides essential information for designing "lab-on-a-chip" systems for synthesizing magnetic nanoparticles, labeling bioparticles with them, and sorting and detecting them on a single chip.

Microfluidic Synthesis, Control, and Sensing of Magnetic Nanoparticles: A Review.

Microfluidic technology is a relatively new field among the various conventional bulk techniques employed for nanomaterial synthesis. Nanoparticles (NPs) produced using such methods generally have poor surface features, morphology, uncontrolled size and broad size distributions. NPs especially used in the biomedical sector require a degree of control over their size, morphology, and polydispersity to improve their functionality. To synthesize such NPs, microfluidic devices are ideal as parameters such as mixing rates, flow rates, mixing volumes, multiphase reactions can be controlled on the micro/nanoscale. There are several strategies and challenges in the synthesis of nanoparticles from organic and inorganic materials in a microfluidic platform. The challenges faced during the design and implementation of these devices, such as the large scale production and interaction with soft lithography materials, which are overcome by the use of the bulk technique in conjugation with microfluidics, use of parallelisation of the processes with the search for new fabrication materials. On the other hand, organ-on-chip (OOC) are analytical microfluidic devices in which cell cutures are present and can mimic an organ along with its physio-chemical properties to study cell-nanoparticle interaction. There are several issues with the construction of such devices as cell cultures within the device can be affected by the fabrication materials. As such new biocompatible materials are being printed into more appropriate designs, utilized to contain said cultures and reduce the risk of error in the analysis of NP properties, such as efficiency and toxicity. This review aims to discuss the recent developments in the field of synthesis as well as toxicity and efficacy evaluations of biomedical nanoparticles using microfluidic technology. 

Recent developments in microfluidic technology for synthesis and toxicity-efficiency studies of biomedical nanomaterials

The introduction of nanoparticles into bone tissue engineering strategies is beneficial to govern cell fate into osteogenesis and the regeneration of large bone defects. The present study explored the role of nanoparticles to advance osteogenesis with a focus on the cellular and molecular pathways involved. Pubmed, Pubmed Central, Embase, Scopus, and Science Direct databases were explored for those published articles relevant to the involvement of nanoparticles in osteogenic cellular pathways. As multifunctional compounds, nanoparticles contribute to scaffold-free and scaffold-based tissue engineering strategies to progress osteogenesis and bone regeneration. They regulate inflammatory responses and osteo/angio/osteoclastic signaling pathways to generate an osteogenic niche. Besides, nanoparticles interact with biomolecules, enhance their half-life and bioavailability. Nanoparticles are promising candidates to promote osteogenesis. However, the interaction of nanoparticles with the biological milieu is somewhat complicated, and more considerations are recommended on the employment of nanoparticles in clinical applications because of NP-induced toxicities.

Application of nanoparticles in bone tissue engineering; a review on the molecular mechanisms driving osteogenesis.

Magnetic iron oxide nanoparticles (MNPs) have been developed and applied for a broad range of biomedical applications, such as diagnostic imaging, magnetic fluid hyperthermia, targeted drug delivery, gene therapy and tissue repair. As one key element, reproducible synthesis routes of MNPs are capable of controlling and adjusting structure, size, shape and magnetic properties are mandatory. In this review, we discuss advanced methods for engineering and utilizing MNPs, such as continuous synthesis approaches using microtechnologies and the biosynthesis of magnetosomes, biotechnological synthesized iron oxide nanoparticles from bacteria. We compare the technologies and resulting MNPs with conventional synthetic routes. Prominent biomedical applications of the MNPs such as diagnostic imaging, magnetic fluid hyperthermia, targeted drug delivery and magnetic actuation in micro/nanorobots will be presented.

Advances in Magnetic Nanoparticles Engineering for Biomedical Applications-A Review.

In recent years, nanotechnology has led to significant scientific and technological advances in diverse fields, specifically within the field of medicine. Owing to the revolutionary implications in drug delivery, nanotechnology-based drug delivery systems have gained an increasing research interest in the current medical field. A variety of nanomaterials with unique physical, chemical and biological properties have been engineered to develop new drug delivery systems for the local, sustained and targeted delivery of drugs with improved therapeutic efficiency and less or no toxicity, representing a very promising approach for the effective management of diseases. The utility of nanotechnology, particularly in the field of orthopedics, is a topic of extensive research. Nanotechnology has a great potential to revolutionize treatment, diagnostics, and research in the field of orthopedics. Nanophase drug delivery has shown great promise in their ability to deliver drugs at nanoscale for a variety of orthopedic applications. In this review, we discuss recent advances in the field of nanostructured drug delivery systems for orthopedic applications.

/pdf/nanotechnology-based-drug-delivery-systems-in-orthopedics-3xgzgak0cu.pdf

Nanotechnology-based drug delivery systems in orthopedics.

Nanostructures are capable of major changes in our life. However, the game changing properties of experimental nanostructures mostly are not repeatable for the industry and it is not easy to produce the amount of nanoparticles necessary for the industrial world. Repeatable methods, which do not require highly trained personnel, for industrial-scale production should be developed to transfer the academic research to the use of people. Although there are various successful microfluidics devices that have been designed for microstructures synthesis, the synthesis of the nanostructures is not an enlightened area and there is a need for research to reach a better state. Especially, the development and design of microfluidics devices for biopolymeric nanoparticles are very important. The biopolymeric nanoparticles have uses in both nanotechnology and nanomedicine especially as theragnostic tools. In this study, a microfluidic device has been modeled, designed, and manufactured for especially iron oxide core chitosan nanoparticles. The microfluidics channels were manufactured by 3D printing. After nanoparticles synthesized by manufactured device, these particles were characterized, and their properties were examined. In addition to the flow rate, chemical concentrations, and pH, the structure of the microfluidics channel and hurdles have effects on the particle size and particle size distribution. Best results were obtained with 120-120ml/h flow rates and 0.06-0.03% concentrations at pH 4.5 for chitosan-tripolyphosphate couple. The nanoparticles that were produced in microchannels with hurdles under these conditions have a DLS measurement of 190±15 nm in diameter with 69% intensity. In conclusion, the 3D printed microfluidic channels are able to synthesize nanoparticles in a reproducible way with or without iron oxide core.

Synthesis of iron oxide core chitosan nanoparticles in a 3D printed microfluidic device

Polymethyl methacrylate (PMMA), called as bone cement, has been used in implant surgery, initially in dental practices, then in arthroplasty surgery for decades. Bone cement is a highly preferred c...

Borate mineral loading into acrylic bone cements to gain cost-effectivity, enhanced antibacterial resistivity, and better cellular integration properties

Immunoaffinity silica nanoparticles as efficient nanoprobes for selectively capturing transferrin molecules

A Comparative Investigation of Nanofiber- and Cryogel-Based Scaffolds for Mesenchymal Stem Cells from Different Tissues

In recent years, there has been an increase in nanoparticle research towards creating better release systems that can maintains the effective dosage over desired periods. Conventional nanoparticle systems have not been successful for this goal. Thus, the aim of this study is to evaluate the sequential release profiles of hybrid materials, combining nanoparticles, hydrogels and bone cement, for the treatment of arthroplasty infections. In this study, Vancomycin, which is one of the most used antibiotics in orthopedics, was loaded to alginate-chitosan nanoparticles. These drug-loaded nanoparticles were dispersed in an alginate gel and the gel covered the polymethylmethacrylate bone cement. After the crosslinking of the gel around the bone cement, the sequential release profile was evaluated for 60 days in vitro. The results of the morphological, chemical characterization and encapsulations studies showed that different loadings of drugs resulted in different encapsulation efficiencies. Although the release profile from the nanoparticles was as expected, the sequential release profile of the combined system has a Fickian type release for a longer time period. In conclusion, the results indicate that combining different release systems can alter the release profile of the system.

Development of a Sequential Antibiotic Releasing System for Two-Stage Total Joint Replacement Surgery.

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