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Authors = Vuk Uskoković ORCID = 0000-0003-3256-1606

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13 pages, 4139 KiB  
Article
Microstructural, Morphological, and Magnetic Effects of NiFe2O4 Shell Formation Around Nanospherical ZnFe2O4 Cores
by Marija Šuljagić, Vuk Uskoković, Lukasz Kilanski, Sabina Lewinska, Abdul Khaliq, Anna Ślawska-Waniewska, Aleksandar Kremenović, Vladimir Pavlović, Dejan A. Jeremić and Ljubica Andjelković
Magnetochemistry 2025, 11(1), 2; https://doi.org/10.3390/magnetochemistry11010002 - 5 Jan 2025
Viewed by 1554
Abstract
First-row transition metal oxides have relatively modest magnetic properties compared to those of permanent magnets based on rare earth elements. However, there is a hope that this gap might be bridged via proper compositional and structural adjustments. Bi-magnetic nanostructures with homogeneous interfaces often [...] Read more.
First-row transition metal oxides have relatively modest magnetic properties compared to those of permanent magnets based on rare earth elements. However, there is a hope that this gap might be bridged via proper compositional and structural adjustments. Bi-magnetic nanostructures with homogeneous interfaces often exhibit a combination or synergy of properties of both phases, resulting in improved performance compared to their monophasic magnetic counterparts. To gain a deeper insight into these complex structures, a bi-magnetic nanostructured material composed of superparamagnetic nanoparticles comprising a zinc ferrite core and a nickel ferrite shell was synthesized using the seed-mediated growth approach. The resulting ZnFe2O4@NiFe2O4 core–shell nanoparticles were characterized using a series of experimental techniques and were compared to the ZnFe2O4 cores. Most importantly, the formation of the NiFe2O4 shell around the ZnFe2O4 core improved the net crystallinity of the material and altered the particle morphology by reducing the convexity of the surface. Simultaneously, the magnetic measurements demonstrated the coherence of the interface between the core and the shell. These effects combined led to improved spin coupling and stronger magnetism, as evidenced by higher saturation magnetization and the doubling of the blocking temperature for the ZnFe2O4@NiFe2O4 core–shell particles relative to the ZnFe2O4 cores. Full article
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13 pages, 2156 KiB  
Article
Tunable Release of Calcium from Chitosan-Coated Bioglass
by Vuk Uskoković, Gabriel Abuna, Joseph Ryan Hampton and Saulo Geraldeli
Pharmaceutics 2024, 16(1), 39; https://doi.org/10.3390/pharmaceutics16010039 - 27 Dec 2023
Cited by 8 | Viewed by 1839
Abstract
Bioglass presents a standard biomaterial for regeneration of hard tissues in orthopedics and dentistry. The notable osteo-inductive properties of bioglass are largely due to the release of calcium ions from it. However, this release is not easily controllable and can often be excessive, [...] Read more.
Bioglass presents a standard biomaterial for regeneration of hard tissues in orthopedics and dentistry. The notable osteo-inductive properties of bioglass are largely due to the release of calcium ions from it. However, this release is not easily controllable and can often be excessive, especially during the initial interaction of the biomaterial with the surrounding tissues. Consequently, this excessive release can deplete the calcium content of the bioglass, ultimately reducing its overall bioactivity. In this study, we have tested if applying biopolymer chitosan coatings of different thicknesses would be able to mitigate and regulate the calcium ion release from monodisperse bioglass nanoparticles. Calcium release was assessed for four different chitosan coating thicknesses at different time points over the period of 28 days using a fluorescence quencher. Expectedly, chitosan-coated particles released less calcium as the concentration of chitosan in the coating solution increased, presumably due to the increased thickness of the chitosan coating around the bioglass particles. The mechanism of release remained constant for each coating thickness, corresponding to anomalous, non-Fickian diffusion, but the degree of anomalousness increased with the deposition of chitosan. Zeta potential testing showed an expected increase in the positive double layer charge following the deposition of the chitosan coating due to the surface exposure of the amine groups of chitosan. Less intuitively, the zeta potential became less positive as thickness of the chitosan coating increased, attesting to the lower density of the surface charges within thicker coatings than within the thinner ones. Overall, the findings of this study demonstrate that chitosan coating efficiently prevents the early release of calcium from bioglass. This coating procedure also allows for the tuning of the calcium release kinetics by controlling the chitosan concentration in the parent solution. Full article
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33 pages, 4929 KiB  
Conference Report
YUCOMAT 2023: An International Advisory Board Member’s Digest
by Vuk Uskoković
Mater. Proc. 2023, 16(1), 1; https://doi.org/10.3390/materproc2023016001 - 24 Oct 2023
Viewed by 4438
Abstract
The 24th edition of the Yugoslav Conference on Materials (YUCOMAT) organized annually by the Materials Research Society of Serbia (MRS-Serbia) was held in Herceg Novi, Montenegro, from 4 September to 8 September 2023. The conference attracted 212 participants and nearly 200 presenters, 17 [...] Read more.
The 24th edition of the Yugoslav Conference on Materials (YUCOMAT) organized annually by the Materials Research Society of Serbia (MRS-Serbia) was held in Herceg Novi, Montenegro, from 4 September to 8 September 2023. The conference attracted 212 participants and nearly 200 presenters, 17 of which were plenary speakers, while the rest were assigned regular oral or poster presentations. The participants came from over 20 different countries of the world, the most represented among which were Serbia, Ukraine, Poland, Czech Republic, United States, Montenegro, Lithuania, Italy, Republic of Korea, Romania, Germany, and China. Outside of the five plenary sessions at YUCOMAT and a special session dedicated to MXenes, the conference was divided to five symposia: (i) advanced methods in synthesis and processing of materials; (ii) advanced materials for high-technology applications; (iii) nanostructured materials; (iv) eco-materials and eco-technologies; and (v) biomaterials. In this report, a member of the International Advisory Board of MRS-Serbia gives a digest of the conference, alongside providing a few historical remarks. Full article
(This article belongs to the Proceedings of YUCOMAT 2023: The 24th Annual Conference on Material Science)
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43 pages, 1379 KiB  
Review
Current and Future Technologies for the Detection of Antibiotic-Resistant Bacteria
by Dina Yamin, Vuk Uskoković, Abubakar Muhammad Wakil, Mohammed Dauda Goni, Shazana Hilda Shamsuddin, Fatin Hamimi Mustafa, Wadha A. Alfouzan, Mohammed Alissa, Amer Alshengeti, Rana H. Almaghrabi, Mona A. Al Fares, Mohammed Garout, Nawal A. Al Kaabi, Ahmad A. Alshehri, Hamza M. Ali, Ali A. Rabaan, Fatimah Abdullah Aldubisi, Chan Yean Yean and Nik Yusnoraini Yusof
Diagnostics 2023, 13(20), 3246; https://doi.org/10.3390/diagnostics13203246 - 18 Oct 2023
Cited by 66 | Viewed by 14044
Abstract
Antibiotic resistance is a global public health concern, posing a significant threat to the effectiveness of antibiotics in treating bacterial infections. The accurate and timely detection of antibiotic-resistant bacteria is crucial for implementing appropriate treatment strategies and preventing the spread of resistant strains. [...] Read more.
Antibiotic resistance is a global public health concern, posing a significant threat to the effectiveness of antibiotics in treating bacterial infections. The accurate and timely detection of antibiotic-resistant bacteria is crucial for implementing appropriate treatment strategies and preventing the spread of resistant strains. This manuscript provides an overview of the current and emerging technologies used for the detection of antibiotic-resistant bacteria. We discuss traditional culture-based methods, molecular techniques, and innovative approaches, highlighting their advantages, limitations, and potential future applications. By understanding the strengths and limitations of these technologies, researchers and healthcare professionals can make informed decisions in combating antibiotic resistance and improving patient outcomes. Full article
(This article belongs to the Section Diagnostic Microbiology and Infectious Disease)
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14 pages, 1442 KiB  
Communication
Paving Way for a Paradigm Shift in Oncology: Curing Cancer by Loving It?
by Vuk Uskoković
Micro 2023, 3(3), 749-762; https://doi.org/10.3390/micro3030053 - 21 Sep 2023
Viewed by 1716
Abstract
Plateaus in the efficacy of traditional methods for the treatment of cancer reached in the last decades call for the exploration of alternative models as their potential clinical complements. Here, the classical view of cancer as a tissue that is to be eradicated [...] Read more.
Plateaus in the efficacy of traditional methods for the treatment of cancer reached in the last decades call for the exploration of alternative models as their potential clinical complements. Here, the classical view of cancer as a tissue that is to be eradicated by methods describable by a compendium of militaristic metaphors is being challenged with a provocative idea: what if cancer can be cured with love condensed down to the level of molecular and cell biology? Correspondingly, the idea that love mimics the traits of the objects of its affection and helps them grow was translated to the level of cell biology by incorporating anti-apoptotic properties in healthy cells and promoting tumorigenesis in cancerous cells. Both the indirect and direct co-culture of the two cell types demonstrated hindered growth of cancer cells relative to that of their primary counterparts when these cellular modifications inspired by love for cancer were being implemented. The two experimental models reported here are emphasized as crude and simplistic methods derived from the idea that cancer may be best treated by being loved at the cellular and molecular biology levels. More comprehensive and effective methods may emanate from continued exploration and expansion of the intriguing and innovative avenue for cancer management proposed here. Full article
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2 pages, 155 KiB  
Editorial
Grand Challenges in Materials Science: A Special Issue
by Vuk Uskoković
Materials 2023, 16(18), 6109; https://doi.org/10.3390/ma16186109 - 7 Sep 2023
Viewed by 1420
Abstract
Materials science has and will continue to be a science at a crossroads [...] Full article
(This article belongs to the Special Issue Grand Challenges in Materials Science)
14 pages, 1626 KiB  
Article
Supplementation of Polymeric Reservoirs with Redox-Responsive Metallic Nanoparticles as a New Concept for the Smart Delivery of Insulin in Diabetes
by Vuk Uskoković
Materials 2023, 16(2), 786; https://doi.org/10.3390/ma16020786 - 13 Jan 2023
Cited by 5 | Viewed by 2594
Abstract
Type 1 diabetes is caused by the inability of the pancreatic beta cells to produce sufficient amounts of insulin, an anabolic hormone promoting the absorption of the blood glucose by various cells in the body, primarily hepatocytes and skeletal muscle cells. This form [...] Read more.
Type 1 diabetes is caused by the inability of the pancreatic beta cells to produce sufficient amounts of insulin, an anabolic hormone promoting the absorption of the blood glucose by various cells in the body, primarily hepatocytes and skeletal muscle cells. This form of impaired metabolism has been traditionally treated with subcutaneous insulin injections. However, because one such method of administration does not directly correspond to the glucose concentrations in the blood and may fail to reduce hyperglycemia or cause hypoglycemia, the delivery of insulin in a glucose-dependent manner has been researched intensely in the present and past. This study tested the novel idea that the supplementation of polymeric reservoirs containing insulin with metallic nanoparticle precursors responsive to the redox effect of glucose could be used to create triggers for the release of insulin in direct response to the concentration of glucose in the tissue. For that purpose, manganese oxide nanoparticles were dispersed inside a poly(ε-caprolactone) matrix loaded with an insulin proxy and the resulting composite was exposed to different concentrations of glucose. The release of the insulin proxy occurred in direct proportion to the concentration of glucose in the medium. Mechanistically, as per the central hypothesis of the study, glucose reduced the manganese cations contained within the metal oxide phase, forming finer and more dissipative zero-valent metallic nanoparticles, thus disrupting the polymeric network, opening up pores in the matrix and facilitating the release of the captured drug. The choice of manganese for this study over other metals was justified by its use as a supplement for protection against diabetes. Numerical analysis of the release mechanism revealed an increasingly nonlinear and anomalous release accompanied by a higher diffusion rate at the expense of chain rigidity as the glucose concentration increased. Future studies should focus on rendering the glucose-controlled release (i) feasible within the physiological pH range and (ii) sensitive to physiologically relevant glucose concentrations. These technical improvements of the fundamental new concept proven here may bring it closer to a real-life application for the mitigation of symptoms of hyperglycemia in patients with diabetes. Full article
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14 pages, 1360 KiB  
Review
The Immunosuppressive Effect of TNFR2 Expression in the Colorectal Cancer Microenvironment
by Nurul Hakimah Mohd Salim, Ali Mussa, Naveed Ahmed, Suhana Ahmad, Chan Yean Yean, Rosline Hassan, Vuk Uskoković, Rohimah Mohamud and Nur Asyilla Che Jalil
Biomedicines 2023, 11(1), 173; https://doi.org/10.3390/biomedicines11010173 - 10 Jan 2023
Cited by 10 | Viewed by 3728
Abstract
Colorectal cancer (CRC) represents one of the most common causes of death among cancers worldwide. Its incidence has been increasing among the young population. Many risk factors contribute to the development and progression of CRC and about 70% of them are sporadic. The [...] Read more.
Colorectal cancer (CRC) represents one of the most common causes of death among cancers worldwide. Its incidence has been increasing among the young population. Many risk factors contribute to the development and progression of CRC and about 70% of them are sporadic. The CRC microenvironment is highly heterogeneous and represents a very complex immunosuppressive platform. Many cytokines and their receptors are vital participants in this immunosuppressive microenvironment. Tumor necrosis factors (TNFs) and TNF receptor 2 (TNFR2) are critical players in the development of CRC. TNFR2 was observed to have increased the immunosuppressive activity of CRC cells via regulatory T cells (T regs) and myeloid-derived suppressor cells (MDSC) in the CRC microenvironment. However, the exact mechanism of TNFR2 in regulating the CRC prognosis remains elusive. Here, we discuss the role of TNFR2 in immune escape mechanism of CRC in the immunosuppressive cells, including Tregs and MDSCs, and the complex signaling pathways that facilitate the development of CRC. It is suggested that extensive studies on TNFR2 downstream signaling must be done, since TNFR2 has a high potential to be developed into a therapeutic agent and cancer biomarker in the future. Full article
(This article belongs to the Special Issue Molecular Research on Colorectal Cancer)
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14 pages, 21307 KiB  
Conference Report
Conference Report: YUCOMAT 2022 & XII World Round Table Conference on Sintering
by Vuk Uskoković
Mater. Proc. 2022, 12(1), 1; https://doi.org/10.3390/materproc2022012001 - 29 Nov 2022
Viewed by 2241
Abstract
Yugoslav Conference on Materials (YUCOMAT) and World Round Table Conference on Sintering (WRTCS) are conferences with a long tradition, having first been held in 1995 and 1969, respectively. From 29 August to 2 September 2022, the Materials Research Society of Serbia (MRS-Serbia) and [...] Read more.
Yugoslav Conference on Materials (YUCOMAT) and World Round Table Conference on Sintering (WRTCS) are conferences with a long tradition, having first been held in 1995 and 1969, respectively. From 29 August to 2 September 2022, the Materials Research Society of Serbia (MRS-Serbia) and the International Institute for the Science of Sintering organized the two conferences jointly, in the town in which they had been inaugurally held: Herceg-Novi, Montenegro. The joint conference attracted around 200 participants, 20 of which were plenary speakers, while the rest were assigned regular oral or poster presentations. The participants came from 25 different countries of the world, the most represented among which were Serbia, Ukraine, Czech Republic, Poland, and the United States. Outside of the four plenary sessions at YUCOMAT and two at the WRTCS, the conference was divided to five symposia: (i) advanced methods in synthesis and processing of materials; (ii) advanced materials for high-technology applications; (iii) nanostructured materials; (iv) eco-materials and eco-technologies; and (v) biomaterials. Here, one of this year’s plenary lecturers at YUCOMAT and a member of the International Advisory Board for the MRS-Serbia gives a formally solicited and unbiased view of the conference, discussing its successful aspects and aspects worth revisiting, alongside providing a few historical remarks. Full article
(This article belongs to the Proceedings of Stand Alone Papers 2022)
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31 pages, 11644 KiB  
Article
Altering Microbiomes with Hydroxyapatite Nanoparticles: A Metagenomic Analysis
by Vuk Uskoković and Victoria M. Wu
Materials 2022, 15(17), 5824; https://doi.org/10.3390/ma15175824 - 24 Aug 2022
Cited by 4 | Viewed by 3039
Abstract
Hydroxyapatite (HAp), the most abundant biological material among mammals, has been recently demonstrated to possess moderate antibacterial properties. Metagenomics provides a series of tools for analyzing the simultaneous interaction of materials with larger communities of microbes, which may aid in optimizing the antibacterial [...] Read more.
Hydroxyapatite (HAp), the most abundant biological material among mammals, has been recently demonstrated to possess moderate antibacterial properties. Metagenomics provides a series of tools for analyzing the simultaneous interaction of materials with larger communities of microbes, which may aid in optimizing the antibacterial activity of a material such as HAp. Here, a microbiome intrinsic to the sample of sandy soil collected from the base of an African Natal plum (Carissa macrocarpa) shrub surrounding the children’s sandbox at the Arrowhead Park in Irvine, California was challenged with HAp nanoparticles and analyzed with next-generation sequencing for hypervariable 16S ribosomal DNA base pair homologies. HAp nanoparticles overwhelmingly reduced the presence of Gram-negative phyla, classes, orders, families, genera and species, and consequently elevated the relative presence of their Gram-positive counterparts. Thermodynamic, electrostatic and chemical bonding arguments were combined in a model proposed to explain this selective affinity. The ability of amphiphilic surface protrusions of lipoteichoic acid in Gram-positive bacteria and mycolic acid in mycobacteria to increase the dispersibility of the bacterial cells and assist in their resistance to capture by the solid phase is highlighted. Within the Gram-negative group, the variability of the distal, O-antigen portion of the membrane lipopolysaccharide was shown to be excessive and the variability of its proximal, lipid A portion insufficient to explain the selectivity based on chemical sequence arguments. Instead, flagella-driven motility proves to be a factor favoring the evasion of binding to HAp. HAp displayed a preference toward binding to less pathogenic bacteria than those causative of disease in humans, while taxa having a positive agricultural effect were largely captured by HAp, indicating an evolutionary advantage this may have given it as a biological material. The capacity to selectively sequester Gram-negative microorganisms and correspondingly alter the composition of the microbiome may open up a new avenue in environmental and biomedical applications of HAp. Full article
(This article belongs to the Special Issue Advances in Antimicrobial Strategies Based on Nanoparticles)
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18 pages, 4654 KiB  
Article
When Nothing Turns Itself Inside out and Becomes Something: Coating Poly(Lactic-Co-Glycolic Acid) Spheres with Hydroxyapatite Nanoparticles vs. the Other Way Around
by Vuk Uskoković and Victoria M. Wu
J. Funct. Biomater. 2022, 13(3), 102; https://doi.org/10.3390/jfb13030102 - 23 Jul 2022
Cited by 6 | Viewed by 2972
Abstract
To stabilize drugs physisorbed on the surface of hydroxyapatite (HAp) nanoparticles and prevent burst release, these nanoparticles are commonly coated with polymers. Bioactive HAp, however, becomes shielded from the surface of such core/shell entities, which partially defeats the purpose of using it. The [...] Read more.
To stabilize drugs physisorbed on the surface of hydroxyapatite (HAp) nanoparticles and prevent burst release, these nanoparticles are commonly coated with polymers. Bioactive HAp, however, becomes shielded from the surface of such core/shell entities, which partially defeats the purpose of using it. The goal of this study was to assess the biological and pharmacokinetic effects of inverting this classical core/shell structure by coating poly(lactic-co-glycolic acid) (PLGA) spheres with HAp nanoparticles. The HAp shell did not hinder the release of vancomycin; rather, it increased the release rate to a minor degree, compared to that from undecorated PLGA spheres. The decoration of PLGA spheres with HAp induced lesser mineral deposition and lesser upregulation of osteogenic markers compared to those induced by the composite particles where HAp nanoparticles were embedded inside the PLGA spheres. This was explained by homeostatic mechanisms governing the cell metabolism, which ensure than the sensation of a product of this metabolism in the cell interior or exterior is met with the reduction in the metabolic activity. The antagonistic relationship between proliferation and bone production was demonstrated by the higher proliferation rate of cells challenged with HAp-coated PLGA spheres than of those treated with PLGA-coated HAp. It is concluded that the overwhelmingly positive response of tissues to HAp-coated biomaterials for bone replacement is unlikely to be due to the direct induction of new bone growth in osteoblasts adhering to the HAp coating. Rather, these positive effects are consequential to more elementary aspects of cell attachment, mechanotransduction, and growth at the site of contact between the HAp-coated material and the tissue. Full article
(This article belongs to the Special Issue Functionalized Biomimetic Calcium Phosphates 2.0)
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33 pages, 2264 KiB  
Review
High-Dose Vitamin C for Cancer Therapy
by Ali Mussa, Ros Akmal Mohd Idris, Naveed Ahmed, Suhana Ahmad, Ahmad Hafiz Murtadha, Tengku Ahmad Damitri Al Astani Tengku Din, Chan Yean Yean, Wan Faiziah Wan Abdul Rahman, Norhafiza Mat Lazim, Vuk Uskoković, Khalid Hajissa, Noor Fatmawati Mokhtar, Rohimah Mohamud and Rosline Hassan
Pharmaceuticals 2022, 15(6), 711; https://doi.org/10.3390/ph15060711 - 3 Jun 2022
Cited by 47 | Viewed by 14998
Abstract
In recent years, the idea that Vitamin C (Vit-C) could be utilized as a form of anti-cancer therapy has generated many contradictory arguments. Recent insights into the physiological characteristics of Vit-C, its pharmacokinetics, and results from preclinical reports, however, suggest that high-dose Vit-C [...] Read more.
In recent years, the idea that Vitamin C (Vit-C) could be utilized as a form of anti-cancer therapy has generated many contradictory arguments. Recent insights into the physiological characteristics of Vit-C, its pharmacokinetics, and results from preclinical reports, however, suggest that high-dose Vit-C could be effectively utilized in the management of various tumor types. Studies have shown that the pharmacological action of Vit-C can attack various processes that cancerous cells use for their growth and development. Here, we discuss the anti-cancer functions of Vit-C, but also the potential for the use of Vit-C as an epigenetic regulator and immunotherapy enhancer. We also provide a short overview of the current state of systems for scavenging reactive oxygen species (ROS), especially in the context of their influencing high-dose Vit-C toxicity for the inhibition of cancer growth. Even though the mechanisms of Vit-C action are promising, they need to be supported with robust randomized and controlled clinical trials. Moreover, upcoming studies should focus on how to define the most suitable cancer patient populations for high-dose Vit-C treatments and develop effective strategies that combine Vit-C with various concurrent cancer treatment regimens. Full article
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25 pages, 42241 KiB  
Article
Radioprotective Role of Vitamins C and E against the Gamma Ray-Induced Damage to the Chemical Structure of Bovine Serum Albumin
by Hajar Zarei, Mostean Bahreinipour, Yahya Sefidbakht, Shokouh Rezaei, Rouhollah Gheisari, Susan Kabudanian Ardestani, Vuk Uskoković and Hiroshi Watabe
Antioxidants 2021, 10(12), 1875; https://doi.org/10.3390/antiox10121875 - 24 Nov 2021
Cited by 10 | Viewed by 3442
Abstract
Radioprotective effects of vitamin C and vitamin E as a water-soluble and a lipid-soluble agent, respectively, were investigated at the molecular level during the imposition of gamma radiation-induced structural changes to bovine serum albumin (BSA) at the therapeutic dose of 3 Gy. Secondary [...] Read more.
Radioprotective effects of vitamin C and vitamin E as a water-soluble and a lipid-soluble agent, respectively, were investigated at the molecular level during the imposition of gamma radiation-induced structural changes to bovine serum albumin (BSA) at the therapeutic dose of 3 Gy. Secondary and tertiary structural changes of control and irradiated BSA samples were investigated using circular dichroism and fluorescence spectroscopy. The preirradiation tests showed nonspecific and reversible binding of vitamins C and E to BSA. Secondary and tertiary structures of irradiated BSA considerably changed in the absence of the vitamins. Upon irradiation, α-helices of BSA transitioned to beta motifs and random coils, and the fluorescence emission intensity decreased relative to nonirradiated BSA. In the presence of the vitamins C or E, however, the irradiated BSA was protected from these structural changes caused by reactive oxygen species (ROS). The two vitamins exhibited different patterns of attachment to the protein surface, as inspected by blind docking, and their mechanisms of protection were different. The hydrophilicity of vitamin C resulted in the predominant scavenging of ROS in the solvent, whereas hydrophobic vitamin E localized on the nonpolar patches of the BSA surface, where it did not only form a barrier for diffusing ROS but also encountered them as an antioxidant and neutralized them thanks to the moderate BSA binding constant. Very low concentrations of vitamins C or E (0.005 mg/mL) appear to be sufficient to prevent the oxidative damage of BSA. Full article
(This article belongs to the Special Issue Reactive Oxygen Species in Different Biological Processes)
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23 pages, 5639 KiB  
Article
Blowup of Accidental Images as a Passageway to Discovery: Insights into the Interaction between Hydroxyapatite Nanoparticles and Human Mesenchymal Stem Cells
by Vuk Uskoković
Appl. Sci. 2020, 10(22), 8204; https://doi.org/10.3390/app10228204 - 19 Nov 2020
Cited by 8 | Viewed by 2865
Abstract
Despite decades of research into the interaction between cells and nanoparticles, there is a lack of consensus regarding how specific physicochemical characteristics of the nanoparticles, including chemical composition, crystallinity, size, morphology, charge, and aspect ratio, among others, govern their internalization and intracellular fate. [...] Read more.
Despite decades of research into the interaction between cells and nanoparticles, there is a lack of consensus regarding how specific physicochemical characteristics of the nanoparticles, including chemical composition, crystallinity, size, morphology, charge, and aspect ratio, among others, govern their internalization and intracellular fate. Methodological novelties offer new perspectives on the same old problematics, and often translate into an improved understanding of the given topic. Inspired by an analogy with the theme of the movie, Lisbon Story, a conceptually unconventional method for gaining insight into the interaction between nanoparticles and cells is proposed here. It involves the random, “Take 1” capture of an atomic force micrograph showing the interaction of human mesenchymal stem cells and clusters of spherical hydroxyapatite nanoparticles with a broad distribution of sizes and shapes, the blowup of its segments, and their detailed qualitative inspection. This method led to the derivation of three illustrative hypotheses, some of which were refuted and some corroborated. Specifically, the presupposition that there is an inverse relationship between the cellular uptake efficiency and the size of nanoparticle clusters was confirmed, both empirically and through a literature meta-analysis, but the idea that the geometry of these clusters affects the uptake was refuted. The definite presence of morphological determinants of the cellular uptake at the level of elementary particles, not clusters thereof, however, was confirmed in an alternative experiment. Likewise, immunofluorescent studies demonstrated that relatively large and irregularly shaped nanoparticle clusters do get internalized and localized to the perinuclear area, where they engage in an intimate interaction with the cell nucleus. The proposed enhancement of the binding between cells and biomaterials by increasing the surface ruffling consequential to the nanoparticle uptake - in analogy with the enhanced cell adhesion achieved by introducing topographic irregularities to smooth biomaterial surfaces - was also confirmed by showing that the uptake improves the stem cell adhesion. The uptake also augmented the stem cell viability and the proliferative capacity of cells reseeded with this internal nanoparticle cargo on a fresh surface, albeit with moderate levels of statistical significance and the caveat of its presumed dependence on the cell type, the nanoparticle chemistry and dose, and the overall stage in the transition of the multipotent cells toward an osteoprogenitor lineage. Full article
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27 pages, 2890 KiB  
Review
Calcium Phosphate as a Key Material for Socially Responsible Tissue Engineering
by Vuk Uskoković and Victoria M. Wu
Materials 2016, 9(6), 434; https://doi.org/10.3390/ma9060434 - 1 Jun 2016
Cited by 37 | Viewed by 7155
Abstract
Socially responsible technologies are designed while taking into consideration the socioeconomic, geopolitical and environmental limitations of regions in which they will be implemented. In the medical context, this involves making therapeutic platforms more accessible and affordable to patients in poor regions of the [...] Read more.
Socially responsible technologies are designed while taking into consideration the socioeconomic, geopolitical and environmental limitations of regions in which they will be implemented. In the medical context, this involves making therapeutic platforms more accessible and affordable to patients in poor regions of the world wherein a given disease is endemic. This often necessitates going against the reigning trend of making therapeutic nanoparticles ever more structurally complex and expensive. However, studies aimed at simplifying materials and formulations while maintaining the functionality and therapeutic response of their more complex counterparts seldom provoke a significant interest in the scientific community. In this review we demonstrate that such compositional simplifications are meaningful when it comes to the design of a solution for osteomyelitis, a disease that is in its natural, non-postoperative form particularly prevalent in the underdeveloped parts of the world wherein poverty, poor sanitary conditions, and chronically compromised defense lines of the immune system are the norm. We show that calcium phosphate nanoparticles, which are inexpensive to make, could be chemically designed to possess the same functionality as a hypothetic mixture additionally composed of: (a) a bone growth factor; (b) an antibiotic for prophylactic or anti-infective purposes; (c) a bisphosphonate as an antiresorptive compound; (d) a viral vector to enable the intracellular delivery of therapeutics; (e) a luminescent dye; (f) a radiographic component; (g) an imaging contrast agent; (h) a magnetic domain; and (i) polymers as viscous components enabling the injectability of the material and acting as carriers for the sustained release of a drug. In particular, calcium phosphates could: (a) produce tunable drug release profiles; (b) take the form of viscous and injectable, self-setting pastes; (c) be naturally osteo-inductive and inhibitory for osteoclastogenesis; (d) intracellularly deliver bioactive compounds; (e) accommodate an array of functional ions; (f) be processed into macroporous constructs for tissue engineering; and (g) be naturally antimicrobial. All in all, we see in calcium phosphates the presence of a protean nature whose therapeutic potentials have been barely tapped into. Full article
(This article belongs to the Special Issue Selected papers from ISN2A2016)
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