Nanomaterials for Biomedical Applications

A special issue of Nanomaterials (ISSN 2079-4991). This special issue belongs to the section "Biology and Medicines".

Deadline for manuscript submissions: closed (31 May 2021) | Viewed by 68901

Special Issue Editors


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Guest Editor
1. School of Mechanical and Manufacturing Engineering, Dublin City University, D09 NA55 Dublin, Ireland
2. Centre for Medical Engineering Research, Dublin City University, D09 NA55 Dublin, Ireland
Interests: biomaterials; tissue engineering; tissue regeneration; drug delivery; biomedical engineering
Special Issues, Collections and Topics in MDPI journals

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Co-Guest Editor

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Co-Guest Editor
School of Mechanical and Manufacturing Engineering, Dublin City University, D09 NA55 Dublin, Ireland
Interests: cartilage; tissue engineering; scaffolds; bone repair; biomaterials; bioprinting
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear colleagues,

We would like to invite you to contribute a short communication, full article, or review to this Special Issue, entitled “Nanomaterials for Biomedical Applications”.

Nanomaterials have become one of the most advanced research fields in the disciplines of chemistry, engineering, solid-state physics, biology and medicine. One explanation for this interest is that nanomaterials demonstrate innovative and frequently advantageous properties compared to conventional materials, which generate the capacity for new technological applications. The use of nanomaterials within the biomedical field offers the potential for many ground-breaking opportunities in the treatment and repair of diseased or damaged tissue or bone cancer as a consequence of bone, cardiac and neurodegenerative disorders, cancer, infection and other diseases. The nanoparticle-based biomaterials and medical devices that have been extensively investigated are predominantly either purely inorganic or organic materials. Specific examples include organic nanomaterials such as dendrimers, hyper-branched organic polymers, liposomes, micelles nanocrystals and polymeric hydrogel nanoparticles have been widely used as therapeutic and imaging agents. More recently, the development of inorganic nanomaterials such as metallic-based nanoparticles, superparamagnetic iron oxide nanoparticles and quantum dots have also generated attention for biomedical applications.

In another applicable example, composite (or hybrid) nanoparticles are comprised of inorganic and organic phases that are capable of not only maintaining the advantageous characteristics of both inorganic and organic nanomaterials, but also demonstrate novel benefits over the individual phases. For example, the potential to combine various organic and inorganic phases in an integrated manner allows for tailored tuning of the properties for biomedical applications. Composite-based nanoparticle systems have also been proposed for the targeted release of diagnostic agents, and also as stimuli-responsive nanocarriers for enhanced therapeutic response. The merging of these nanomaterials with research studies to identify genes, proteins and metabolites linked with human disease and the application of a system biology approach to design and develop new diagnostics tools and more focused therapies for patients, will significantly influence the future of healthcare research and development and clinical translation.

In this Special Issue of Nanomaterials, we expect contributions from a wide community of engineers and scientists working on diverse applications relating to the design, synthesis, characterisation, manufacture and translation of nanotechnology in biomedical engineering and interdisciplinary teams focusing on nanotechnology-enabled innovative solutions for biomedical research, diagnostics and advanced therapeutic approaches. As the safety of novel nanomaterials intended for the use in humans remains of primary importance, we also anticipate manuscripts dealing with these aspects of nanotechnology and nanomedicine in this Special Issue.

Prof. Nicholas Dunne
Dr. Tanya Levingstone
Prof. Helen McCarthy
Guest Editors

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Nanomaterials is an international peer-reviewed open access semimonthly journal published by MDPI.

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Keywords

  • biosensing
  • biomedical imaging
  • cancer
  • cardiovascular disease
  • diagnostics
  • infection
  • neurological diseases
  • orthopeadics
  • tissue regeneration
  • protein delivery
  • gene delivery
  • magnetic hyperthermia
  • photodynamic therapy
  • photothermal therapy
  • theranostics
  • nanoparticle synthesis and characterisation
  • nanoparticle manufacture and processing
  • nanoparticle safety

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Published Papers (17 papers)

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20 pages, 4061 KiB  
Article
Computational Indicator Approach for Assessment of Nanotoxicity of Two-Dimensional Nanomaterials
by Alexey A. Tsukanov, Boris Turk, Olga Vasiljeva and Sergey G. Psakhie
Nanomaterials 2022, 12(4), 650; https://doi.org/10.3390/nano12040650 - 15 Feb 2022
Cited by 15 | Viewed by 2542
Abstract
The increasing growth in the development of various novel nanomaterials and their biomedical applications has drawn increasing attention to their biological safety and potential health impact. The most commonly used methods for nanomaterial toxicity assessment are based on laboratory experiments. In recent years, [...] Read more.
The increasing growth in the development of various novel nanomaterials and their biomedical applications has drawn increasing attention to their biological safety and potential health impact. The most commonly used methods for nanomaterial toxicity assessment are based on laboratory experiments. In recent years, with the aid of computer modeling and data science, several in silico methods for the cytotoxicity prediction of nanomaterials have been developed. An affordable, cost-effective numerical modeling approach thus can reduce the need for in vitro and in vivo testing and predict the properties of designed or developed nanomaterials. We propose here a new in silico method for rapid cytotoxicity assessment of two-dimensional nanomaterials of arbitrary chemical composition by using free energy analysis and molecular dynamics simulations, which can be expressed by a computational indicator of nanotoxicity (CIN2D). We applied this approach to five well-known two-dimensional nanomaterials promising for biomedical applications: graphene, graphene oxide, layered double hydroxide, aloohene, and hexagonal boron nitride nanosheets. The results corroborate the available laboratory biosafety data for these nanomaterials, supporting the applicability of the developed method for predictive nanotoxicity assessment of two-dimensional nanomaterials. Full article
(This article belongs to the Special Issue Nanomaterials for Biomedical Applications)
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19 pages, 8055 KiB  
Article
Nanoscale Strontium-Substituted Hydroxyapatite Pastes and Gels for Bone Tissue Regeneration
by Caroline J. Harrison, Paul V. Hatton, Piergiorgio Gentile and Cheryl A. Miller
Nanomaterials 2021, 11(6), 1611; https://doi.org/10.3390/nano11061611 - 19 Jun 2021
Cited by 13 | Viewed by 3690
Abstract
Injectable nanoscale hydroxyapatite (nHA) systems are highly promising biomaterials to address clinical needs in bone tissue regeneration, due to their excellent biocompatibility, bioinspired nature, and ability to be delivered in a minimally invasive manner. Bulk strontium-substituted hydroxyapatite (SrHA) is reported to encourage bone [...] Read more.
Injectable nanoscale hydroxyapatite (nHA) systems are highly promising biomaterials to address clinical needs in bone tissue regeneration, due to their excellent biocompatibility, bioinspired nature, and ability to be delivered in a minimally invasive manner. Bulk strontium-substituted hydroxyapatite (SrHA) is reported to encourage bone tissue growth by stimulating bone deposition and reducing bone resorption, but there are no detailed reports describing the preparation of a systematic substitution up to 100% at the nanoscale. The aim of this work was therefore to fabricate systematic series (0–100 atomic% Sr) of SrHA pastes and gels using two different rapid-mixing methodological approaches, wet precipitation and sol-gel. The full range of nanoscale SrHA materials were successfully prepared using both methods, with a measured substitution very close to the calculated amounts. As anticipated, the SrHA samples showed increased radiopacity, a beneficial property to aid in vivo or clinical monitoring of the material in situ over time. For indirect methods, the greatest cell viabilities were observed for the 100% substituted SrHA paste and gel, while direct viability results were most likely influenced by material disaggregation in the tissue culture media. It was concluded that nanoscale SrHAs were superior biomaterials for applications in bone surgery, due to increased radiopacity and improved biocompatibility. Full article
(This article belongs to the Special Issue Nanomaterials for Biomedical Applications)
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17 pages, 3738 KiB  
Article
Cryochemical Production of Drug Nanoforms: Particle Size and Crystal Phase Control of the Antibacterial Medication 2,3-Quinoxalinedimethanol-1,4-dioxide (Dioxidine)
by Tatyana I. Shabatina, Yurii N. Morosov, Andrey V. Soloviev, Andrey V. Shabatin, Olga I. Vernaya and Michail Y. Melnikov
Nanomaterials 2021, 11(6), 1588; https://doi.org/10.3390/nano11061588 - 17 Jun 2021
Cited by 8 | Viewed by 2161
Abstract
Increasing the effectiveness of known, well-tested drugs is a promising low-cost alternative to the search for new drug molecular forms. Powerful approaches to solve this problem are (a) an active drug particle size reduction down to the nanoscale and (b) thermodynamically metastable but [...] Read more.
Increasing the effectiveness of known, well-tested drugs is a promising low-cost alternative to the search for new drug molecular forms. Powerful approaches to solve this problem are (a) an active drug particle size reduction down to the nanoscale and (b) thermodynamically metastable but kinetically stable crystal modifications of drug acquisition. The combined cryochemical method has been used for size and structural modifications of the antibacterial drug 2,3-quinoxalinedimethanol-1,4-dioxide (dioxidine). The main stage of the proposed technique includes the formation of a molecular vapor of the drug substance, combined with a carrier gas (CO2) flow, followed by a fast condensation of the drug substance and CO2 molecules on a cooled-by-liquid nitrogen surface of preparative cryostate. It was established that the molecular chemical structure of the drug substance remained unchanged during cryochemical modification; however, it led to a significant decrease of the drug particles’ size down to nanosizes and changes in the crystal structures of the solid drug nanoforms obtained. Varying carrier gas (CO2) flow led to changes in their solid phase composition. A higher dissolution rate and changes in antibacterial activity were demonstrated for cryomodified dioxidine samples in comparison to the properties of the initial pharmacopeia dioxidine. Full article
(This article belongs to the Special Issue Nanomaterials for Biomedical Applications)
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20 pages, 3608 KiB  
Article
Photothermal Response Induced by Nanocage-Coated Artificial Extracellular Matrix Promotes Neural Stem Cell Differentiation
by Seunghyun Jung, Nathaniel Harris, Isabelle I. Niyonshuti, Samir V. Jenkins, Abdallah M. Hayar, Fumiya Watanabe, Azemat Jamshidi-Parsian, Jingyi Chen, Michael J. Borrelli and Robert J. Griffin
Nanomaterials 2021, 11(5), 1216; https://doi.org/10.3390/nano11051216 - 4 May 2021
Cited by 12 | Viewed by 3013
Abstract
Strategies to increase the proportion of neural stem cells that differentiate into neurons are vital for therapy of neurodegenerative disorders. In vitro, the extracellular matrix composition and topography have been found to be important factors in stem cell differentiation. We have developed a [...] Read more.
Strategies to increase the proportion of neural stem cells that differentiate into neurons are vital for therapy of neurodegenerative disorders. In vitro, the extracellular matrix composition and topography have been found to be important factors in stem cell differentiation. We have developed a novel artificial extracellular matrix (aECM) formed by attaching gold nanocages (AuNCs) to glass coverslips. After culturing rat neural stem cells (rNSCs) on these gold nanocage-coated surfaces (AuNC-aECMs), we observed that 44.6% of rNSCs differentiated into neurons compared to only 27.9% for cells grown on laminin-coated glass coverslips. We applied laser irradiation to the AuNC-aECMs to introduce precise amounts of photothermally induced heat shock in cells. Our results showed that laser-induced thermal stimulation of AuNC-aECMs further enhanced neuronal differentiation (56%) depending on the laser intensity used. Response to these photothermal effects increased the expression of heat shock protein 27, 70, and 90α in rNSCs. Analysis of dendritic complexity showed that this thermal stimulation promoted neuronal maturation by increasing dendrite length as thermal dose was increased. In addition, we found that cells growing on AuNC-aECMs post laser irradiation exhibited action potentials and increased the expression of voltage-gated Na+ channels compared to laminin-coated glass coverslips. These results indicate that the photothermal response induced in cells growing on AuNC-aECMs can be used to produce large quantities of functional neurons, with improved electrochemical properties, that can potentially be transplanted into a damaged central nervous system to provide replacement neurons and restore lost function. Full article
(This article belongs to the Special Issue Nanomaterials for Biomedical Applications)
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20 pages, 4530 KiB  
Article
Collagen Film Activation with Nanoscale IKVAV-Capped Dendrimers for Selective Neural Cell Response
by Jessica J. Kim, Daniel V. Bax, Robert Murphy, Serena M. Best and Ruth E. Cameron
Nanomaterials 2021, 11(5), 1157; https://doi.org/10.3390/nano11051157 - 28 Apr 2021
Cited by 7 | Viewed by 2710
Abstract
Biocompatible neural guidance conduits are alternatives to less abundant autologous tissue grafts for small nerve gap injuries. To address larger peripheral nerve injuries, it is necessary to design cell selective biomaterials that attract neuronal and/or glial cells to an injury site while preventing [...] Read more.
Biocompatible neural guidance conduits are alternatives to less abundant autologous tissue grafts for small nerve gap injuries. To address larger peripheral nerve injuries, it is necessary to design cell selective biomaterials that attract neuronal and/or glial cells to an injury site while preventing the intrusion of fibroblasts that cause inhibitory scarring. Here, we investigate a potential method for obtaining this selective cellular response by analysing the responses of rat Schwann cells and human dermal fibroblasts to isoleucine-lysine-valine-alanine-valine (IKVAV)-capped dendrimer-activated collagen films. A high quantity of nanoscale IKVAV-capped dendrimers incorporated onto pre-crosslinked collagen films promoted rat Schwann cell attachment and proliferation, and inhibited human dermal fibroblast proliferation. In addition, while pre-crosslinked dendrimer-activated films inhibited fibroblast proliferation, non-crosslinked dendrimer-activated films and films that were crosslinked after dendrimer-activation (post-crosslinked films) did not. The different cellular responses to pre-crosslinked and post-crosslinked films highlight the importance of having fully exposed, non-covalently bound biochemical motifs (pre-crosslinked films) directing certain cellular responses. These results also suggest that high concentrations of nanoscale IKVAV motifs can inhibit fibroblast attachment to biological substrates, such as collagen, which inherently attract fibroblasts. Therefore, this work points toward the potential of IKVAV-capped dendrimer-activated collagen biomaterials in limiting neuropathy caused by fibrotic scarring at peripheral nerve injury sites. Full article
(This article belongs to the Special Issue Nanomaterials for Biomedical Applications)
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19 pages, 5889 KiB  
Article
SiO2-Ag Composite as a Highly Virucidal Material: A Roadmap that Rapidly Eliminates SARS-CoV-2
by Marcelo Assis, Luiz Gustavo P. Simoes, Guilherme C. Tremiliosi, Dyovani Coelho, Daniel T. Minozzi, Renato I. Santos, Daiane C. B. Vilela, Jeziel Rodrigues do Santos, Lara Kelly Ribeiro, Ieda Lucia Viana Rosa, Lucia Helena Mascaro, Juan Andrés and Elson Longo
Nanomaterials 2021, 11(3), 638; https://doi.org/10.3390/nano11030638 - 4 Mar 2021
Cited by 46 | Viewed by 7749
Abstract
COVID-19, as the cause of a global pandemic, has resulted in lockdowns all over the world since early 2020. Both theoretical and experimental efforts are being made to find an effective treatment to suppress the virus, constituting the forefront of current global safety [...] Read more.
COVID-19, as the cause of a global pandemic, has resulted in lockdowns all over the world since early 2020. Both theoretical and experimental efforts are being made to find an effective treatment to suppress the virus, constituting the forefront of current global safety concerns and a significant burden on global economies. The development of innovative materials able to prevent the transmission, spread, and entry of COVID-19 pathogens into the human body is currently in the spotlight. The synthesis of these materials is, therefore, gaining momentum, as methods providing nontoxic and environmentally friendly procedures are in high demand. Here, a highly virucidal material constructed from SiO2-Ag composite immobilized in a polymeric matrix (ethyl vinyl acetate) is presented. The experimental results indicated that the as-fabricated samples exhibited high antibacterial activity towards Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) as well as towards SARS-CoV-2. Based on the present results and radical scavenger experiments, we propose a possible mechanism to explain the enhancement of the biocidal activity. In the presence of O2 and H2O, the plasmon-assisted surface mechanism is the major reaction channel generating reactive oxygen species (ROS). We believe that the present strategy based on the plasmonic effect would be a significant contribution to the design and preparation of efficient biocidal materials. This fundamental research is a precedent for the design and application of adequate technology to the next-generation of antiviral surfaces to combat SARS-CoV-2. Full article
(This article belongs to the Special Issue Nanomaterials for Biomedical Applications)
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20 pages, 6011 KiB  
Article
Antibacterial Properties of Plasma-Activated Perfluorinated Substrates with Silver Nanoclusters Deposition
by Petr Slepička, Silvie Rimpelová, Nikola Slepičková Kasálková, Dominik Fajstavr, Petr Sajdl, Zdeňka Kolská and Václav Švorčík
Nanomaterials 2021, 11(1), 182; https://doi.org/10.3390/nano11010182 - 13 Jan 2021
Cited by 11 | Viewed by 2653
Abstract
This article is focused on the evaluation of surface properties of polytetrafluoroethylene (PTFE) nanotextile and a tetrafluoroethylene-perfluoro(alkoxy vinyl ether) (PFA) film and their surface activation with argon plasma treatment followed with silver nanoclusters deposition. Samples were subjected to plasma modification for a different [...] Read more.
This article is focused on the evaluation of surface properties of polytetrafluoroethylene (PTFE) nanotextile and a tetrafluoroethylene-perfluoro(alkoxy vinyl ether) (PFA) film and their surface activation with argon plasma treatment followed with silver nanoclusters deposition. Samples were subjected to plasma modification for a different time exposure, silver deposition for different time periods, or their combination. As an alternative approach, the foils were coated with poly-L-lactic acid (PLLA) and silver. The following methods were used to study the surface properties of the polymers: goniometry, atomic force microscopy, and X-ray photoelectron microscopy. By combining the aforementioned methods for material surface modification, substrates with antibacterial properties eliminating the growth of Gram-positive and Gram-negative bacteria were prepared. Studies of antimicrobial activity showed that PTFE plasma-modified samples coated with PLLA and deposited with a thin layer of Ag had a strong antimicrobial effect, which was also observed for the PFA material against the bacterial strain of S. aureus. Significant antibacterial effect against S. aureus, Proteus sp. and E. coli has been demonstrated on PTFE nanotextile plasma-treated for 240 s, coated with PLLA, and subsequently sputtered with thin Ag layer. Full article
(This article belongs to the Special Issue Nanomaterials for Biomedical Applications)
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16 pages, 2384 KiB  
Article
Improving the Intercellular Uptake and Osteogenic Potency of Calcium Phosphate via Nanocomplexation with the RALA Peptide
by Michelle O’Doherty, Eoghan J. Mulholland, Philip Chambers, Sreekanth Pentlavalli, Monika Ziminska, Marine J. Chalanqui, Hannah M. Pauly, Binulal N. Sathy, Tammy H. Donahue, Daniel J. Kelly, Nicholas Dunne and Helen O. McCarthy
Nanomaterials 2020, 10(12), 2442; https://doi.org/10.3390/nano10122442 - 7 Dec 2020
Cited by 6 | Viewed by 3008
Abstract
Calcium phosphate-base materials (e.g., alpha tri-calcium phosphate (α–TCP)) have been shown to promote osteogenic differentiation of stem/progenitor cells, enhance osteoblast osteogenic activity and mediate in vivo bone tissue formation. However, variable particle size and hydrophilicity of the calcium phosphate result in an extremely [...] Read more.
Calcium phosphate-base materials (e.g., alpha tri-calcium phosphate (α–TCP)) have been shown to promote osteogenic differentiation of stem/progenitor cells, enhance osteoblast osteogenic activity and mediate in vivo bone tissue formation. However, variable particle size and hydrophilicity of the calcium phosphate result in an extremely low bioavailability. Therefore, an effective delivery system is required that can encapsulate the calcium phosphate, improve cellular entry and, consequently, elicit a potent osteogenic response in osteoblasts. In this study, collagenous matrix deposition and extracellular matrix mineralization of osteoblast lineage cells were assessed to investigate osteogenesis following intracellular delivery of α-TCP nanoparticles. The nanoparticles were formed via condensation with a novel, cationic 30 mer amphipathic peptide (RALA). Nanoparticles prepared at a mass ratio of 5:1 demonstrated an average particle size of 43 nm with a zeta potential of +26 mV. The average particle size and zeta potential remained stable for up to 28 days at room temperature and across a range of temperatures (4–37 °C). Cell viability decreased 24 h post-transfection following RALA/α-TCP nanoparticle treatment; however, recovery ensued by Day 7. Immunocytochemistry staining for Type I collagen up to Day 21 post-transfection with RALA/α-TCP nanoparticles (NPs) in MG-63 cells exhibited a significant enhancement in collagen expression and deposition compared to an untreated control. Furthermore, in porcine mesenchymal stem cells (pMSCs), there was enhanced mineralization compared to α–TCP alone. Taken together these data demonstrate that internalization of RALA/α-TCP NPs elicits a potent osteogenic response in both MG-63 and pMSCs. Full article
(This article belongs to the Special Issue Nanomaterials for Biomedical Applications)
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17 pages, 5526 KiB  
Article
Highly Efficient Antimicrobial Activity of CuxFeyOz Nanoparticles against Important Human Pathogens
by Lu Zhu, David W. Pearson, Stéphane L. Benoit, Jing Xie, Jitendra Pant, Yanjun Yang, Arnab Mondal, Hitesh Handa, Jane Y. Howe, Yen-Con Hung, Jorge E. Vidal, Robert J. Maier and Yiping Zhao
Nanomaterials 2020, 10(11), 2294; https://doi.org/10.3390/nano10112294 - 20 Nov 2020
Cited by 7 | Viewed by 3281
Abstract
The development of innovative antimicrobial materials is crucial in thwarting infectious diseases caused by microbes, as drug-resistant pathogens are increasing in both number and capacity to detoxify the antimicrobial drugs used today. An ideal antimicrobial material should inhibit a wide variety of bacteria [...] Read more.
The development of innovative antimicrobial materials is crucial in thwarting infectious diseases caused by microbes, as drug-resistant pathogens are increasing in both number and capacity to detoxify the antimicrobial drugs used today. An ideal antimicrobial material should inhibit a wide variety of bacteria in a short period of time, be less or not toxic to normal cells, and the fabrication or synthesis process should be cheap and easy. We report a one-step microwave-assisted hydrothermal synthesis of mixed composite CuxFeyOz (Fe2O3/Cu2O/CuO/CuFe2O) nanoparticles (NPs) as an excellent antimicrobial material. The 1 mg/mL CuxFeyOz NPs with the composition 36% CuFeO2, 28% Cu2O and 36% Fe2O3 have a general antimicrobial activity greater than 5 log reduction within 4 h against nine important human pathogenic bacteria (including drug-resistant bacteria as well as Gram-positive and Gram-negative strains). For example, they induced a >9 log reduction in Escherichia coli B viability after 15 min of incubation, and an ~8 log reduction in multidrug-resistant Klebsiella pneumoniae after 4 h incubation. Cytotoxicity tests against mouse fibroblast cells showed about 74% viability when exposed to 1 mg/mL CuxFeyOz NPs for 24 h, compared to the 20% viability for 1 mg/mL pure Cu2O NPs synthesized by the same method. These results show that the CuxFeyOz composite NPs are a highly efficient, low-toxicity and cheap antimicrobial material that has promising potential for applications in medical and food safety. Full article
(This article belongs to the Special Issue Nanomaterials for Biomedical Applications)
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17 pages, 2564 KiB  
Article
Effect of TiO2 Nanotube Pore Diameter on Human Mesenchymal Stem Cells and Human Osteoblasts
by Juan Shong Khaw, Christopher R. Bowen and Sarah H. Cartmell
Nanomaterials 2020, 10(11), 2117; https://doi.org/10.3390/nano10112117 - 25 Oct 2020
Cited by 23 | Viewed by 2766
Abstract
The pore diameter of uniformly structured nanotubes can significantly change the behaviour of cells. Recent studies demonstrated that the activation of integrins is affected not by only the surface chemistry between the cell-material interfaces, but also by the features of surface nanotopography, including [...] Read more.
The pore diameter of uniformly structured nanotubes can significantly change the behaviour of cells. Recent studies demonstrated that the activation of integrins is affected not by only the surface chemistry between the cell-material interfaces, but also by the features of surface nanotopography, including nanotube diameter. While research has been carried out in this area, there has yet to be a single systemic study to date that succinctly compares the response of both human stem cells and osteoblasts to a range of TiO2 nanotube pore diameters using controlled experiments in a single laboratory. In this paper, we investigate the influence of surface nanotopography on cellular behaviour and osseointegrative properties through a systemic study involving human mesenchymal stem cells (hMSCs) and human osteoblasts (HOBs) on TiO2 nanotubes of 20 nm, 50 nm and 100 nm pore diameters using in-vitro assessments. This detailed study demonstrates the interrelationship between cellular behaviour and nanotopography, revealing that a 20 nm nanotube pore diameter is preferred by hMSCs for the induction of osteogenic differentiation, while 50 nm nanotubular structures are favourable by HOBs for osteoblastic maturation. Full article
(This article belongs to the Special Issue Nanomaterials for Biomedical Applications)
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18 pages, 4169 KiB  
Article
Perfluoropolyether Nanoemulsion Encapsulating Chlorin e6 for Sonodynamic and Photodynamic Therapy of Hypoxic Tumor
by Liang Hong, Artem M. Pliss, Ye Zhan, Wenhan Zheng, Jun Xia, Liwei Liu, Junle Qu and Paras N. Prasad
Nanomaterials 2020, 10(10), 2058; https://doi.org/10.3390/nano10102058 - 19 Oct 2020
Cited by 24 | Viewed by 4451
Abstract
Sonodynamic therapy (SDT) has emerged as an important modality for cancer treatment. SDT utilizes ultrasound excitation, which overcomes the limitations of light penetration in deep tumors, as encountered by photodynamic therapy (PDT) which uses optical excitations. A comparative study of these modalities using [...] Read more.
Sonodynamic therapy (SDT) has emerged as an important modality for cancer treatment. SDT utilizes ultrasound excitation, which overcomes the limitations of light penetration in deep tumors, as encountered by photodynamic therapy (PDT) which uses optical excitations. A comparative study of these modalities using the same sensitizer drug can provide an assessment of their effects. However, the efficiency of SDT and PDT is low in a hypoxic tumor environment, which limits their applications. In this study, we report a hierarchical nanoformulation which contains a Food and Drug Administration (FDA) approved sensitizer chlorin, e6, and a uniquely stable high loading capacity oxygen carrier, perfluoropolyether. This oxygen carrier possesses no measurable cytotoxicity. It delivers oxygen to overcome hypoxia, and at the same time, boosts the efficiency of both SDT and PDT. Moreover, we comparatively analyzed the efficiency of SDT and PDT for tumor treatment throughout the depth of the tissue. Our study demonstrates that the strengths of PDT and SDT could be combined into a single multifunctional nanoplatform, which works well in the hypoxia environment and overcomes the limitations of each modality. The combination of deep tissue penetration by ultrasound and high spatial activation by light for selective treatment of single cells will significantly enhance the scope for therapeutic applications. Full article
(This article belongs to the Special Issue Nanomaterials for Biomedical Applications)
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15 pages, 2602 KiB  
Article
Osteogenic and Anti-Inflammatory Behavior of Injectable Calcium Phosphate Loaded with Therapeutic Drugs
by Ines Fasolino, Alessandra Soriente, Luigi Ambrosio and Maria Grazia Raucci
Nanomaterials 2020, 10(9), 1743; https://doi.org/10.3390/nano10091743 - 3 Sep 2020
Cited by 10 | Viewed by 2814
Abstract
Bone fractures related to musculoskeletal disorders determine long-term disability in older people with a consequent significant economic burden. The recovery of pathologically impaired tissue architecture allows avoiding bone loss-derived consequences such as bone height reduction, deterioration of bone structure, inflamed bone pain, and [...] Read more.
Bone fractures related to musculoskeletal disorders determine long-term disability in older people with a consequent significant economic burden. The recovery of pathologically impaired tissue architecture allows avoiding bone loss-derived consequences such as bone height reduction, deterioration of bone structure, inflamed bone pain, and high mortality for thighbone fractures. Actually, standard therapy for osteoporosis treatment is based on the systemic administration of biphosphonates and anti-inflammatory drugs, which entail several side effects including gastrointestinal (GI) diseases, fever, and articular pain. Hence, the demand of innovative therapeutic approaches for locally treating bone lesions has been increasing in the last few years. In this scenario, the development of injectable materials loaded with therapeutically active agents (i.e., anti-inflammatory drugs, antibiotics, and peptides mimicking growth factors) could be an effective tool to treat bone loss and inflammation related to musculoskeletal diseases, including osteoporosis and osteoarthritis. According to this challenge, here, we propose three different compositions of injectable calcium phosphates (CaP) as new carrier materials of therapeutic compounds such as bisphosphonates (i.e., alendronate), anti-inflammatory drugs (i.e., diclofenac sodium), and natural molecules (i.e., harpagoside) for the local bone disease treatment. Biological quantitative analyses were performed for screening osteoinductive and anti-inflammatory properties of injectable drug-loaded systems. Meanwhile, cell morphological features were analyzed through scanning electron microscopy and confocal investigations. The results exhibited that the three systems exerted an osteoinductive effect during later phases of osteogenesis. Simultaneously, all compositions showed an anti-inflammatory activity on inflammation in vitro models. Full article
(This article belongs to the Special Issue Nanomaterials for Biomedical Applications)
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16 pages, 3883 KiB  
Article
Mucoadhesive Nanoparticles for Drug Delivery to the Anterior Eye
by Nicole Mangiacotte, Graeme Prosperi-Porta, Lina Liu, Megan Dodd and Heather Sheardown
Nanomaterials 2020, 10(7), 1400; https://doi.org/10.3390/nano10071400 - 18 Jul 2020
Cited by 8 | Viewed by 3957
Abstract
While the use of topical drops for the delivery of drugs to the anterior of the eye is well accepted, it is far from efficient with as little as 5% of the drug instilled on the eye actually reaching the target tissue. The [...] Read more.
While the use of topical drops for the delivery of drugs to the anterior of the eye is well accepted, it is far from efficient with as little as 5% of the drug instilled on the eye actually reaching the target tissue. The ability to prolong the residence time on the eye is desirable. Based on the acceptability of 2-hydroxyethyl methacrylate based polymers in contact lens applications, the current work focuses on the development of a poly(2-hydroxyethyl methacrylate (HEMA)) nanoparticle system. The particles were modified to allow for degradation and to permit mucoadhesion. Size and morphological analysis of the final polymer products showed that nano-sized, spherical particles were produced. FTIR spectra demonstrated that the nanoparticles comprised poly(HEMA) and that 3-(acrylamido)phenylboronic acid (3AAPBA), as a mucoadhesive, was successfully incorporated. Degradation of nanoparticles containing N,N′-bis(acryloyl)cystamine (BAC) after incubation with DL-dithiothreitol (DTT) was confirmed by a decrease in turbidity and through transmission electron microscopy (TEM). Nanoparticle mucoadhesion was shown through an in-vitro zeta potential analysis. Full article
(This article belongs to the Special Issue Nanomaterials for Biomedical Applications)
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19 pages, 3084 KiB  
Article
Endothelial Cell Targeting by cRGD-Functionalized Polymeric Nanoparticles under Static and Flow Conditions
by Lucía Martínez-Jothar, Arjan D. Barendrecht, Anko M. de Graaff, Sabrina Oliveira, Cornelus F. van Nostrum, Raymond M. Schiffelers, Wim E. Hennink and Marcel H. A. M. Fens
Nanomaterials 2020, 10(7), 1353; https://doi.org/10.3390/nano10071353 - 10 Jul 2020
Cited by 22 | Viewed by 4220
Abstract
Since αvβ3 integrin is a key component of angiogenesis in health and disease, Arg-Gly-Asp (RGD) peptide-functionalized nanocarriers have been investigated as vehicles for targeted delivery of drugs to the αvβ3 integrin-overexpressing neovasculature of tumors. In this work, [...] Read more.
Since αvβ3 integrin is a key component of angiogenesis in health and disease, Arg-Gly-Asp (RGD) peptide-functionalized nanocarriers have been investigated as vehicles for targeted delivery of drugs to the αvβ3 integrin-overexpressing neovasculature of tumors. In this work, PEGylated nanoparticles (NPs) based on poly(lactic-co-glycolic acid) (PLGA) functionalized with cyclic-RGD (cRGD), were evaluated as nanocarriers for the targeting of angiogenic endothelium. For this purpose, NPs (~300 nm) functionalized with cRGD with different surface densities were prepared by maleimide-thiol chemistry and their interactions with human umbilical vein endothelial cells (HUVECs) were evaluated under different conditions using flow cytometry and microscopy. The cell association of cRGD-NPs under static conditions was time-, concentration- and cRGD density-dependent. The interactions between HUVECs and cRGD-NPs dispersed in cell culture medium under flow conditions were also time- and cRGD density-dependent. When washed red blood cells (RBCs) were added to the medium, a 3 to 8-fold increase in NPs association to HUVECs was observed. Moreover, experiments conducted under flow in the presence of RBC at physiologic hematocrit and shear rate, are a step forward in the prediction of in vivo cell–particle association. This approach has the potential to assist development and high-throughput screening of new endothelium-targeted nanocarriers. Full article
(This article belongs to the Special Issue Nanomaterials for Biomedical Applications)
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14 pages, 4822 KiB  
Article
Antibacterial Activity of Silver Nanoparticles (AgNP) Confined to Mesostructured, Silica-Based Calcium Phosphate against Methicillin-Resistant Staphylococcus aureus (MRSA)
by Jung-Chang Kung, Wei-Hsun Wang, Chung-Lin Lee, Hao-Che Hsieh and Chi-Jen Shih
Nanomaterials 2020, 10(7), 1264; https://doi.org/10.3390/nano10071264 - 28 Jun 2020
Cited by 17 | Viewed by 2980
Abstract
Staphylococcus aureus, which is commonly found in hospitals, has become a major problem in infection control. In this study, Ag/80S bioactive ceramics used for enhanced antibacterial applications have been developed. An in vitro bioactivity test of the Ag/80S bioactive ceramic powders was [...] Read more.
Staphylococcus aureus, which is commonly found in hospitals, has become a major problem in infection control. In this study, Ag/80S bioactive ceramics used for enhanced antibacterial applications have been developed. An in vitro bioactivity test of the Ag/80S bioactive ceramic powders was performed in a phosphate-buffered saline (PBS). To explore the antibacterial activity of the Ag/80S bioactive ceramic powders, the Kirby-Bauer susceptibility test, the kinetics of microbial growth analysis and the colony-forming capacity assay were used to determine their minimum inhibitory concentration (MIC) against methicillin-resistant Staphylococcus aureus (MRSA). The results confirmed that the Ag/80S bioactive ceramic powders have antibacterial activity against MRSA (ATCC 33592) and MRSA (ATCC 49476). Full article
(This article belongs to the Special Issue Nanomaterials for Biomedical Applications)
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Review

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13 pages, 1056 KiB  
Review
Nanomaterial Databases: Data Sources for Promoting Design and Risk Assessment of Nanomaterials
by Zuowei Ji, Wenjing Guo, Sugunadevi Sakkiah, Jie Liu, Tucker A. Patterson and Huixiao Hong
Nanomaterials 2021, 11(6), 1599; https://doi.org/10.3390/nano11061599 - 18 Jun 2021
Cited by 27 | Viewed by 6339
Abstract
Nanomaterials have drawn increasing attention due to their tunable and enhanced physicochemical and biological performance compared to their conventional bulk materials. Owing to the rapid expansion of the nano-industry, large amounts of data regarding the synthesis, physicochemical properties, and bioactivities of nanomaterials have [...] Read more.
Nanomaterials have drawn increasing attention due to their tunable and enhanced physicochemical and biological performance compared to their conventional bulk materials. Owing to the rapid expansion of the nano-industry, large amounts of data regarding the synthesis, physicochemical properties, and bioactivities of nanomaterials have been generated. These data are a great asset to the scientific community. However, the data are on diverse aspects of nanomaterials and in different sources and formats. To help utilize these data, various databases on specific information of nanomaterials such as physicochemical characterization, biomedicine, and nano-safety have been developed and made available online. Understanding the structure, function, and available data in these databases is needed for scientists to select appropriate databases and retrieve specific information for research on nanomaterials. However, to our knowledge, there is no study to systematically compare these databases to facilitate their utilization in the field of nanomaterials. Therefore, we reviewed and compared eight widely used databases of nanomaterials, aiming to provide the nanoscience community with valuable information about the specific content and function of these databases. We also discuss the pros and cons of these databases, thus enabling more efficient and convenient utilization. Full article
(This article belongs to the Special Issue Nanomaterials for Biomedical Applications)
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30 pages, 10572 KiB  
Review
Engineered Extracellular Vesicles: Tailored-Made Nanomaterials for Medical Applications
by Kenny Man, Mathieu Y. Brunet, Marie-Christine Jones and Sophie C. Cox
Nanomaterials 2020, 10(9), 1838; https://doi.org/10.3390/nano10091838 - 15 Sep 2020
Cited by 71 | Viewed by 8351
Abstract
Extracellular vesicles (EVs) are emerging as promising nanoscale therapeutics due to their intrinsic role as mediators of intercellular communication, regulating tissue development and homeostasis. The low immunogenicity and natural cell-targeting capabilities of EVs has led to extensive research investigating their potential as novel [...] Read more.
Extracellular vesicles (EVs) are emerging as promising nanoscale therapeutics due to their intrinsic role as mediators of intercellular communication, regulating tissue development and homeostasis. The low immunogenicity and natural cell-targeting capabilities of EVs has led to extensive research investigating their potential as novel acellular tools for tissue regeneration or for the diagnosis of pathological conditions. However, the clinical use of EVs has been hindered by issues with yield and heterogeneity. From the modification of parental cells and naturally-derived vesicles to the development of artificial biomimetic nanoparticles or the functionalisation of biomaterials, a multitude of techniques have been employed to augment EVs therapeutic efficacy. This review will explore various engineering strategies that could promote EVs scalability and therapeutic effectiveness beyond their native utility. Herein, we highlight the current state-of-the-art EV-engineering techniques with discussion of opportunities and obstacles for each. This is synthesised into a guide for selecting a suitable strategy to maximise the potential efficacy of EVs as nanoscale therapeutics. Full article
(This article belongs to the Special Issue Nanomaterials for Biomedical Applications)
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