International Journal of Molecular Sciences

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19 pages, 16015 KiB

Open AccessArticle

Superior Osteo-Inductive and Osteo-Conductive Properties of Trabecular Titanium vs. PEEK Scaffolds on Human Mesenchymal Stem Cells: A Proof of Concept for the Use of Fusion Cages

by Enrico Ragni, Carlotta Perucca Orfei, Alessandro Bidossi, Elena De Vecchi, Natale Francaviglia, Alberto Romano, Gianluca Maestretti, Fulvio Tartara and Laura de Girolamo

Int. J. Mol. Sci. 2021, 22(5), 2379; https://doi.org/10.3390/ijms22052379 - 27 Feb 2021

Cited by 9 | Viewed by 2814

Abstract

Fusion cages composed of titanium and its alloys are emerging as valuable alternative to standard polyetheretherketone (PEEK) ones routinely used in cervical and lumbar spine surgery. Aim of this study was to evaluate osteo-inductive and osteo-conductive ability of an innovative trabecular titanium (T-Ti) [...] Read more.

Fusion cages composed of titanium and its alloys are emerging as valuable alternative to standard polyetheretherketone (PEEK) ones routinely used in cervical and lumbar spine surgery. Aim of this study was to evaluate osteo-inductive and osteo-conductive ability of an innovative trabecular titanium (T-Ti) scaffold on human mesenchymal stem cells (hMSCs), in both absence and presence of biochemical osteogenic stimuli. Same abilities were assessed on PEEK and standard 2D plastic surface, the latter meant as gold-standard for in vitro differentiation studies. hMSCs adhered and colonized both T-Ti and PEEK scaffolds. In absence of osteogenic factors, T-Ti triggered osteogenic induction of MSCs, as demonstrated by alkaline phosphatase activity and calcium deposition increments, while PEEK and standard 2D did not. Addition of osteogenic stimuli reinforced osteogenic differentiation of hMSCs cultured on T-Ti in a significantly higher manner with respect to standard 2D plastic culture surfaces, whereas PEEK almost completely abolished the process. T-Ti driven differentiation towards osteoblasts was confirmed by gene and marker expression analyses, even in absence of osteogenic stimuli. These results clearly indicate superior in vitro osteo-inductive and osteo-conductive capacity of T-Ti compared to PEEK, and make ground for further studies supporting the use of T-Ti cages to improve bone fusion. Full article

(This article belongs to the Special Issue Cell-Biomaterial Interaction 2020)

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15 pages, 3226 KiB

Open AccessArticle

Biomimetic Mineralization Promotes Viability and Differentiation of Human Mesenchymal Stem Cells in a Perfusion Bioreactor

by Gloria Belén Ramírez-Rodríguez, Ana Rita Pereira, Marietta Herrmann, Jan Hansmann, José Manuel Delgado-López, Simone Sprio, Anna Tampieri and Monica Sandri

Int. J. Mol. Sci. 2021, 22(3), 1447; https://doi.org/10.3390/ijms22031447 - 1 Feb 2021

Cited by 14 | Viewed by 3338

Abstract

In bone tissue engineering, the design of 3D systems capable of recreating composition, architecture and micromechanical environment of the native extracellular matrix (ECM) is still a challenge. While perfusion bioreactors have been proposed as potential tool to apply biomechanical stimuli, its use has [...] Read more.

In bone tissue engineering, the design of 3D systems capable of recreating composition, architecture and micromechanical environment of the native extracellular matrix (ECM) is still a challenge. While perfusion bioreactors have been proposed as potential tool to apply biomechanical stimuli, its use has been limited to a low number of biomaterials. In this work, we propose the culture of human mesenchymal stem cells (hMSC) in biomimetic mineralized recombinant collagen scaffolds with a perfusion bioreactor to simultaneously provide biochemical and biophysical cues guiding stem cell fate. The scaffolds were fabricated by mineralization of recombinant collagen in the presence of magnesium (RCP.MgAp). The organic matrix was homogeneously mineralized with apatite nanocrystals, similar in composition to those found in bone. X-Ray microtomography images revealed isotropic porous structure with optimum porosity for cell ingrowth. In fact, an optimal cell repopulation through the entire scaffolds was obtained after 1 day of dynamic seeding in the bioreactor. Remarkably, RCP.MgAp scaffolds exhibited higher cell viability and a clear trend of up-regulation of osteogenic genes than control (non-mineralized) scaffolds. Results demonstrate the potential of the combination of biomimetic mineralization of recombinant collagen in presence of magnesium and dynamic culture of hMSC as a promising strategy to closely mimic bone ECM. Full article

(This article belongs to the Special Issue Cell-Biomaterial Interaction 2020)

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25 pages, 5875 KiB

Open AccessArticle

Synthesis and Characterization of Mesoporous Mg- and Sr-Doped Nanoparticles for Moxifloxacin Drug Delivery in Promising Tissue Engineering Applications

by Georgia K. Pouroutzidou, Liliana Liverani, Anna Theocharidou, Ioannis Tsamesidis, Maria Lazaridou, Evi Christodoulou, Anastasia Beketova, Christina Pappa, Konstantinos S. Triantafyllidis, Antonios D. Anastasiou, Lambrini Papadopoulou, Dimitrios N. Bikiaris, Aldo R. Boccaccini and Eleana Kontonasaki

Int. J. Mol. Sci. 2021, 22(2), 577; https://doi.org/10.3390/ijms22020577 - 8 Jan 2021

Cited by 37 | Viewed by 5048

Abstract

Mesoporous silica-based nanoparticles (MSNs) are considered promising drug carriers because of their ordered pore structure, which permits high drug loading and release capacity. The dissolution of Si and Ca from MSNs can trigger osteogenic differentiation of stem cells towards extracellular matrix calcification, while [...] Read more.

Mesoporous silica-based nanoparticles (MSNs) are considered promising drug carriers because of their ordered pore structure, which permits high drug loading and release capacity. The dissolution of Si and Ca from MSNs can trigger osteogenic differentiation of stem cells towards extracellular matrix calcification, while Mg and Sr constitute key elements of bone biology and metabolism. The aim of this study was the synthesis and characterization of sol–gel-derived MSNs co-doped with Ca, Mg and Sr. Their physico-chemical properties were investigated by X-ray diffraction (XRD), scanning electron microscopy with energy dispersive X-ray analysis (SEM/EDX), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), X-ray fluorescence spectroscopy (XRF), Brunauer Emmett Teller and Brunauer Joyner Halenda (BET/BJH), dynamic light scattering (DLS) and ζ-potential measurements. Moxifloxacin loading and release profiles were assessed with high performance liquid chromatography (HPLC) cell viability on human periodontal ligament fibroblasts and their hemolytic activity in contact with human red blood cells (RBCs) at various concentrations were also investigated. Doped MSNs generally retained their textural characteristics, while different compositions affected particle size, hemolytic activity and moxifloxacin loading/release profiles. All co-doped MSNs revealed the formation of hydroxycarbonate apatite on their surface after immersion in simulated body fluid (SBF) and promoted mitochondrial activity and cell proliferation. Full article

(This article belongs to the Special Issue Cell-Biomaterial Interaction 2020)

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16 pages, 1987 KiB

Open AccessArticle

Evaluation of the Physicochemical Properties, Pharmacokinetics, and In Vitro Anticancer Effects of Docetaxel and Osthol Encapsulated in Methoxy Poly(ethylene glycol)-b-Poly(caprolactone) Polymeric Micelles

by Min Jeong Jo, Yu Jin Lee, Chun-Woong Park, Youn Bok Chung, Jin-Seok Kim, Mi Kyeong Lee and Dae Hwan Shin

Int. J. Mol. Sci. 2021, 22(1), 231; https://doi.org/10.3390/ijms22010231 - 28 Dec 2020

Cited by 15 | Viewed by 3413

Abstract

Docetaxel (DTX), a taxane-based anticancer drug, and osthol (OTH), a coumarin-derivative compound, have shown anticancer effects against different types of cancers through various mechanisms. However, these drugs have low solubility in water and low oral bioavailability, and thus their clinical application is difficult. [...] Read more.

Docetaxel (DTX), a taxane-based anticancer drug, and osthol (OTH), a coumarin-derivative compound, have shown anticancer effects against different types of cancers through various mechanisms. However, these drugs have low solubility in water and low oral bioavailability, and thus their clinical application is difficult. To overcome these problems, we encapsulated DTX and OTH in methoxy poly(ethylene glycol)-b-poly(caprolactone) (mPEG-b-PCL) and conducted studies in vitro and in vivo. We selected a 1:4 ratio as the optimal ratio of DTX and OTH, through combination index analysis in A549 cancer cells, and prepared micelles to evaluate the encapsulation efficiency, drug loading, particle size, and zeta potential. The in vitro drug-release profile showed that DTX/OTH-loaded mPEG-b-PCL micelles could slowly release DTX and OTH. In the clonogenic assay, DTX/OTH-loaded mPEG-b-PCL micelles showed 3.7 times higher inhibitory effect than the DTX/OTH solution. Pharmacokinetic studies demonstrated that micelles in combination with DTX and OTH exhibited increased area under curve and decreased clearance values, as compared with single micelles. Full article

(This article belongs to the Special Issue Cell-Biomaterial Interaction 2020)

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11 pages, 1819 KiB

Open AccessArticle

Recontamination of Healthcare Surfaces by Repeated Wiping with Biocide-Loaded Wipes: “One Wipe, One Surface, One Direction, Dispose” as Best Practice in the Clinical Environment

by Nicholas W. M. Edwards, Emma L. Best, Parikshit Goswami, Mark H. Wilcox and Stephen J. Russell

Int. J. Mol. Sci. 2020, 21(24), 9659; https://doi.org/10.3390/ijms21249659 - 18 Dec 2020

Cited by 8 | Viewed by 2577

Abstract

The wiping of high-touch healthcare surfaces made of metals, ceramics and plastics to remove bacteria is an accepted tool in combatting the transmission of healthcare-associated infections (HCAIs). In practice, surfaces may be repeatedly wiped using a single wipe, and the potential for recontamination [...] Read more.

The wiping of high-touch healthcare surfaces made of metals, ceramics and plastics to remove bacteria is an accepted tool in combatting the transmission of healthcare-associated infections (HCAIs). In practice, surfaces may be repeatedly wiped using a single wipe, and the potential for recontamination may be affected by various factors. Accordingly, we studied how the surface to be wiped, the type of fibre in the wipe and how the presence of liquid biocide affected the degree of recontamination. Experiments were conducted using metal, ceramic and plastic healthcare surfaces, and two different wipe compositions (hygroscopic and hydrophilic), with and without liquid biocide. Despite initially high removal efficiencies of >70% during initial wiping, all healthcare surfaces were recontaminated with E. coli, S. aureus and E. faecalis when wiped more than once using the same wipe. Recontamination occurred regardless of the fibre composition of the wipe or the presence of a liquid biocide. The extent of recontamination by E. coli, S. aureus and E. faecalis bacteria also increased when metal healthcare surfaces possessed a higher microscale roughness (<1 μm), as determined by Atomic Force Microscopy (AFM). The high propensity for healthcare surfaces to be re-contaminated following initial wiping suggests that a “One wipe, One surface, One direction, Dispose” policy should be implemented and rigorously enforced. Full article

(This article belongs to the Special Issue Cell-Biomaterial Interaction 2020)

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23 pages, 3987 KiB

Open AccessArticle

Unpatterned Bioactive Poly(Butylene 1,4-Cyclohexanedicarboxylate)-Based Film Fast Induced Neuronal-Like Differentiation of Human Bone Marrow-Mesenchymal Stem Cells

by Francesco Morena, Chiara Argentati, Michelina Soccio, Ilaria Bicchi, Francesca Luzi, Luigi Torre, Andrea Munari, Carla Emiliani, Matteo Gigli, Nadia Lotti, Ilaria Armentano and Sabata Martino

Int. J. Mol. Sci. 2020, 21(23), 9274; https://doi.org/10.3390/ijms21239274 - 4 Dec 2020

Cited by 11 | Viewed by 2448

Abstract

Herein, we present poly(butylene 1,4-cyclohexanedicarboxylate) (PBCE) films characterized by an unpatterned microstructure and a specific hydrophobicity, capable of boosting a drastic cytoskeleton architecture remodeling, culminating with the neuronal-like differentiation of human bone marrow-mesenchymal stem cells (hBM-MSCs). We have used two different filming procedures [...] Read more.

Herein, we present poly(butylene 1,4-cyclohexanedicarboxylate) (PBCE) films characterized by an unpatterned microstructure and a specific hydrophobicity, capable of boosting a drastic cytoskeleton architecture remodeling, culminating with the neuronal-like differentiation of human bone marrow-mesenchymal stem cells (hBM-MSCs). We have used two different filming procedures to prepare the films, solvent casting (PBCE) and compression-moulding (PBCE*). PBCE film had a rough and porous surface with spherulite-like aggregations (Ø = 10–20 μm) and was characterized by a water contact angle = 100°. PBCE* showed a smooth and continuous surface without voids and visible spherulite-like aggregations and was more hydrophobic (WCA = 110°). Both surface characteristics were modulated through the copolymerization of different amounts of ether-oxygen-containing co-units into PBCE chemical structure. We showed that only the surface characteristics of PBCE-solvent-casted films steered hBM-MSCs toward a neuronal-like differentiation. hBM-MSCs lost their canonical mesenchymal morphology, acquired a neuronal polarized shape with a long cell protrusion (≥150 μm), expressed neuron-specific class III β-tubulin and microtubule-associated protein 2 neuronal markers, while nestin, a marker of uncommitted stem cells, was drastically silenced. These events were observed as early as 2-days after cell seeding. Of note, the phenomenon was totally absent on PBCE* film, as hBM-MSCs maintained the mesenchymal shape and behavior and did not express neuronal/glial markers. Full article

(This article belongs to the Special Issue Cell-Biomaterial Interaction 2020)

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10 pages, 4481 KiB

Open AccessArticle

Smooth Muscle Cell Responses to Poly(ε-Caprolactone) Triacrylate Networks with Different Crosslinking Time

by Jing Wang, Li Liu, Aoning Wang, Xiang Liu, Yi Zhang, Zhoulu Wang and Jinbo Dou

Int. J. Mol. Sci. 2020, 21(23), 8932; https://doi.org/10.3390/ijms21238932 - 25 Nov 2020

Viewed by 1944

Abstract

Poly(ε-caprolactone) triacrylate (PCLTA) is attractive in tissue engineering because of its good biocompatibility and processability. The crosslinking time strongly influences PCLTAs cellular behaviors. To investigate these influences, PCLTAs with different molecular weights were crosslinked under UV light for times ranging from 1 to [...] Read more.

Poly(ε-caprolactone) triacrylate (PCLTA) is attractive in tissue engineering because of its good biocompatibility and processability. The crosslinking time strongly influences PCLTAs cellular behaviors. To investigate these influences, PCLTAs with different molecular weights were crosslinked under UV light for times ranging from 1 to 20 min. The crosslinking efficiency of PCLTA increased with decreasing the molecular weight and increasing crosslinking time which could increase the gel fraction and network stiffness and decrease the swelling ratio. Then, the PCLTA networks crosslinked for different time were used as substrates for culturing rat aortic smooth muscle cells (SMCs). SMC attachment and proliferation all increased when the PCLTA molecular weight increased from 8k to 10k and then to 20k at the same crosslinking time. For the same PCLTA, SMC attachment, proliferation, and focal adhesions increased with increasing the crosslinking time, in particular, between the substrates crosslinked for less than 3 min and longer than 5 min. This work will provide a good experimental basis for the application of PCLTA. Full article

(This article belongs to the Special Issue Cell-Biomaterial Interaction 2020)

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15 pages, 8378 KiB

Open AccessArticle

Coumarin-Modified CQDs for Biomedical Applications—Two-Step Synthesis and Characterization

by Łukasz Janus, Julia Radwan-Pragłowska, Marek Piątkowski and Dariusz Bogdał

Int. J. Mol. Sci. 2020, 21(21), 8073; https://doi.org/10.3390/ijms21218073 - 29 Oct 2020

Cited by 15 | Viewed by 3950

Abstract

Waste biomass such as lignin constitutes a great raw material for eco-friendly carbon quantum dots (CQDs) synthesis, which find numerous applications in various fields of industry and medicine. Carbon nanodots, due to their unique luminescent properties as well as water-solubility and biocompatibility, are [...] Read more.

Waste biomass such as lignin constitutes a great raw material for eco-friendly carbon quantum dots (CQDs) synthesis, which find numerous applications in various fields of industry and medicine. Carbon nanodots, due to their unique luminescent properties as well as water-solubility and biocompatibility, are superior to traditional organic dyes. Thus, obtainment of CQDs with advanced properties can contribute to modern diagnosis and cell visualization method development. In this article, a new type of coumarin-modified CQD was obtained via a hybrid, two-step pathway consisting of hydrothermal carbonization and microwave-assisted surface modification with coumarin-3-carboxylic acid and 7-(Diethylamino) coumarin-3-carboxylate. The ready products were characterized over their chemical structure and morphology. The nanomaterials were confirmed to have superior fluorescence characteristics and quantum yield up to 18.40%. They also possessed the ability of biomolecules and ion detection due to the fluorescence quenching phenomena. Their lack of cytotoxicity to L929 mouse fibroblasts was confirmed by XTT assay. Moreover, the CQDs were proven over their applicability in real-time bioimaging. Obtained results clearly demonstrated that proposed surface-modified carbon quantum dots may become a powerful tool applicable in nanomedicine and pharmacy. Full article

(This article belongs to the Special Issue Cell-Biomaterial Interaction 2020)

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23 pages, 3620 KiB

Open AccessArticle

Proposing Urothelial and Muscle In Vitro Cell Models as a Novel Approach for Assessment of Long-Term Toxicity of Nanoparticles

by Matej Skočaj, Maruša Bizjak, Klemen Strojan, Jasna Lojk, Mateja Erdani Kreft, Katarina Miš, Sergej Pirkmajer, Vladimir Boštjan Bregar, Peter Veranič and Mojca Pavlin

Int. J. Mol. Sci. 2020, 21(20), 7545; https://doi.org/10.3390/ijms21207545 - 13 Oct 2020

Cited by 5 | Viewed by 2338

Abstract

Many studies evaluated the short-term in vitro toxicity of nanoparticles (NPs); however, long-term effects are still not adequately understood. Here, we investigated the potential toxic effects of biomedical (polyacrylic acid and polyethylenimine coated magnetic NPs) and two industrial (SiO₂ and TiO₂ [...] Read more.

Many studies evaluated the short-term in vitro toxicity of nanoparticles (NPs); however, long-term effects are still not adequately understood. Here, we investigated the potential toxic effects of biomedical (polyacrylic acid and polyethylenimine coated magnetic NPs) and two industrial (SiO₂ and TiO₂) NPs following different short-term and long-term exposure protocols on two physiologically different in vitro models that are able to differentiate: L6 rat skeletal muscle cell line and biomimetic normal porcine urothelial (NPU) cells. We show that L6 cells are more sensitive to NP exposure then NPU cells. Transmission electron microscopy revealed an uptake of NPs into L6 cells but not NPU cells. In L6 cells, we obtained a dose-dependent reduction in cell viability and increased reactive oxygen species (ROS) formation after 24 h. Following continuous exposure, more stable TiO₂ and polyacrylic acid (PAA) NPs increased levels of nuclear factor Nrf2 mRNA, suggesting an oxidative damage-associated response. Furthermore, internalized magnetic PAA and TiO₂ NPs hindered the differentiation of L6 cells. We propose the use of L6 skeletal muscle cells and NPU cells as a novel approach for assessment of the potential long-term toxicity of relevant NPs that are found in the blood and/or can be secreted into the urine. Full article

(This article belongs to the Special Issue Cell-Biomaterial Interaction 2020)

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15 pages, 2312 KiB

Open AccessArticle

Analysis of the Direct and Indirect Effects of Nanoparticle Exposure on Microglial and Neuronal Cells In Vitro

by Jasna Lojk, Lea Babič, Petra Sušjan, Vladimir Boštjan Bregar, Mojca Pavlin, Iva Hafner-Bratkovič and Peter Veranič

Int. J. Mol. Sci. 2020, 21(19), 7030; https://doi.org/10.3390/ijms21197030 - 24 Sep 2020

Cited by 2 | Viewed by 2453

Abstract

Environmental or biomedical exposure to nanoparticles (NPs) can results in translocation and accumulation of NPs in the brain, which can lead to health-related problems. NPs have been shown to induce toxicity to neuronal cells through several direct mechanisms, but only a few studies [...] Read more.

Environmental or biomedical exposure to nanoparticles (NPs) can results in translocation and accumulation of NPs in the brain, which can lead to health-related problems. NPs have been shown to induce toxicity to neuronal cells through several direct mechanisms, but only a few studies have also explored the indirect effects of NPs, through consequences due to the exposure of neighboring cells to NPs. In this study, we analysed possible direct and indirect effects of NPs (polyacrylic acid (PAA) coated cobalt ferrite NP, TiO₂ P25 and maghemite NPs) on immortalized mouse microglial cells and differentiated CAD mouse neuronal cells in monoculture (direct toxicity) or in transwell co-culture system (indirect toxicity). We showed that although the low NP concentrations (2–25 µg/mL) did not induce changes in cell viability, cytokine secretion or NF-κB activation of microglial cells, even low NP concentrations of 10 µg/mL can affect the cells and change their secretion of protein stress mediators. These can in turn influence neuronal cells in indirect exposure model. Indirect toxicity of NPs is an important and not adequately assessed mechanism of NP toxicity, since it not only affects cells on the exposure sites, but through secretion of signaling mediators, can also affect cells that do not come in direct contact with NPs. Full article

(This article belongs to the Special Issue Cell-Biomaterial Interaction 2020)

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14 pages, 3776 KiB

Open AccessArticle

GO Nanosheets: Promising Nano Carrier for the S29, 1-(2-Chloro-2-(4-chlorophenyl-ethyl)-N-(4-fluorobenzyl)-1H-pyrazolo[3,4-d] pyrimidin-4-amine, Therapeutic Agent in Neuroblastoma

by Stefania Mardente, Michele Aventaggiato, Emanuela Mari, Antonio Francioso, Marco Tafani, Luciana Mosca, Alessandra Zicari, Igor Malyshev, Larisa Kuznetsova and Federica Valentini

Int. J. Mol. Sci. 2020, 21(17), 6430; https://doi.org/10.3390/ijms21176430 - 3 Sep 2020

Cited by 2 | Viewed by 2515

Abstract

Graphene oxide (GO) derivatives are reported as a valid alternative to conventional carriers of therapeutic agents, because they have a large surface area, an excellent electrical and thermal conductivity and a great capacity for selective binding of drugs and therapeutics, due to the [...] Read more.

Graphene oxide (GO) derivatives are reported as a valid alternative to conventional carriers of therapeutic agents, because they have a large surface area, an excellent electrical and thermal conductivity and a great capacity for selective binding of drugs and therapeutics, due to the functionalization of their surfaces, edges and sides. In this work GO nanosheets, synthesized by electrochemical exfoliation of graphite (patent N 102015000023739, Tor Vergata University), were investigated as possible carriers of an anticancer drug, the S29, an inhibitor of a cytoplasmic tyrosine kinase (c-SRC) on a neuroblastoma cell line (SK N BE 2 cells). Neuroblastoma is a heterogenous tumor whose characteristics range from spontaneous regression to aggressive phenotypes that are due to different mutations that often occur in SRC family kinases. Inhibitors of tyrosine kinases are currently investigated for their anti-tumoral effects on aggressive neuroblastomas, but their uptake in cells and pharmacokinetics needs to be improved. In this work S29 was stably conjugated with highly water-dispersible GO nanoparticles. S29/GO complex formation was induced by 1h sonication and its stability was analyzed by chromatography coupled with spectrophotometry and mass spectrometry. The synthesized composite (GO-S29) was delivered into SK N BE 2 cells and its effects on cell viability, production of reactive oxygen species (ROS) and migration were studied. The results show that the compound GO-S29 exerts anti-tumoral effects on the neuroblastoma cell line, higher than both GO and S29 do alone and that GO has an additive effect on S29. Full article

(This article belongs to the Special Issue Cell-Biomaterial Interaction 2020)

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18 pages, 2125 KiB

Open AccessArticle

Towards Mimicking the Fetal Liver Niche: The Influence of Elasticity and Oxygen Tension on Hematopoietic Stem/Progenitor Cells Cultured in 3D Fibrin Hydrogels

by Christian Garcia-Abrego, Samantha Zaunz, Burak Toprakhisar, Ramesh Subramani, Olivier Deschaume, Stijn Jooken, Manmohan Bajaj, Herman Ramon, Catherine Verfaillie, Carmen Bartic and Jennifer Patterson

Int. J. Mol. Sci. 2020, 21(17), 6367; https://doi.org/10.3390/ijms21176367 - 2 Sep 2020

Cited by 11 | Viewed by 5097

Abstract

Hematopoietic stem/progenitor cells (HSPCs) are responsible for the generation of blood cells throughout life. It is believed that, in addition to soluble cytokines and niche cells, biophysical cues like elasticity and oxygen tension are responsible for the orchestration of stem cell fate. Although [...] Read more.

Hematopoietic stem/progenitor cells (HSPCs) are responsible for the generation of blood cells throughout life. It is believed that, in addition to soluble cytokines and niche cells, biophysical cues like elasticity and oxygen tension are responsible for the orchestration of stem cell fate. Although several studies have examined the effects of bone marrow (BM) niche elasticity on HSPC behavior, no study has yet investigated the effects of the elasticity of other niche sites like the fetal liver (FL), where HSPCs expand more extensively. In this study, we evaluated the effect of matrix stiffness values similar to those of the FL on BM-derived HSPC expansion. We first characterized the elastic modulus of murine FL tissue at embryonic day E14.5. Fibrin hydrogels with similar stiffness values as the FL (soft hydrogels) were compared with stiffer fibrin hydrogels (hard hydrogels) and with suspension culture. We evaluated the expansion of total nucleated cells (TNCs), Lin⁻/cKit⁺ cells, HSPCs (Lin⁻/Sca⁺/cKit⁺ (LSK) cells), and hematopoietic stem cells (HSCs: LSK- Signaling Lymphocyte Activated Molecule (LSK-SLAM) cells) when cultured in 5% O₂ (hypoxia) or in normoxia. After 10 days, there was a significant expansion of TNCs and LSK cells in all culture conditions at both levels of oxygen tension. LSK cells expanded more in suspension culture than in both fibrin hydrogels, whereas TNCs expanded more in suspension culture and in soft hydrogels than in hard hydrogels, particularly in normoxia. The number of LSK-SLAM cells was maintained in suspension culture and in the soft hydrogels but not in the hard hydrogels. Our results indicate that both suspension culture and fibrin hydrogels allow for the expansion of HSPCs and more differentiated progeny whereas stiff environments may compromise LSK-SLAM cell expansion. This suggests that further research using softer hydrogels with stiffness values closer to the FL niche is warranted. Full article

(This article belongs to the Special Issue Cell-Biomaterial Interaction 2020)

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14 pages, 4264 KiB

Open AccessArticle

Carbon Fibers as a New Type of Scaffold for Midbrain Organoid Development

by Anna Tejchman, Agnieszka Znój, Paula Chlebanowska, Aneta Frączek-Szczypta and Marcin Majka

Int. J. Mol. Sci. 2020, 21(17), 5959; https://doi.org/10.3390/ijms21175959 - 19 Aug 2020

Cited by 13 | Viewed by 3824

Abstract

The combination of induced pluripotent stem cell (iPSC) technology and 3D cell culture creates a unique possibility for the generation of organoids that mimic human organs in in vitro cultures. The use of iPS cells in organoid cultures enables the differentiation of cells [...] Read more.

The combination of induced pluripotent stem cell (iPSC) technology and 3D cell culture creates a unique possibility for the generation of organoids that mimic human organs in in vitro cultures. The use of iPS cells in organoid cultures enables the differentiation of cells into dopaminergic neurons, also found in the human midbrain. However, long-lasting organoid cultures often cause necrosis within organoids. In this work, we present carbon fibers (CFs) for medical use as a new type of scaffold for organoid culture, comparing them to a previously tested copolymer poly-(lactic-co-glycolic acid) (PLGA) scaffold. We verified the physicochemical properties of CF scaffolds compared to PLGA in improving the efficiency of iPSC differentiation within organoids. The physicochemical properties of carbon scaffolds such as porosity, microstructure, or stability in the cellular environment make them a convenient material for creating in vitro organoid models. Through screening several genes expressed during the differentiation of organoids at crucial brain stages of development, we found that there is a correlation between PITX3, one of the key regulators of terminal differentiation, and the survival of midbrain dopaminergic (mDA) neurons and tyrosine hydroxylase (TH) gene expression. This makes organoids formed on carbon scaffolds an improved model containing mDA neurons convenient for studying midbrain-associated neurodegenerative diseases such as Parkinson’s disease. Full article

(This article belongs to the Special Issue Cell-Biomaterial Interaction 2020)

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Review

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28 pages, 5748 KiB

Open AccessReview

Silk Fibroin as a Functional Biomaterial for Tissue Engineering

by Weizhen Sun, David Alexander Gregory, Mhd Anas Tomeh and Xiubo Zhao

Int. J. Mol. Sci. 2021, 22(3), 1499; https://doi.org/10.3390/ijms22031499 - 2 Feb 2021

Cited by 283 | Viewed by 21421

Abstract

Tissue engineering (TE) is the approach to combine cells with scaffold materials and appropriate growth factors to regenerate or replace damaged or degenerated tissue or organs. The scaffold material as a template for tissue formation plays the most important role in TE. Among [...] Read more.

Tissue engineering (TE) is the approach to combine cells with scaffold materials and appropriate growth factors to regenerate or replace damaged or degenerated tissue or organs. The scaffold material as a template for tissue formation plays the most important role in TE. Among scaffold materials, silk fibroin (SF), a natural protein with outstanding mechanical properties, biodegradability, biocompatibility, and bioresorbability has attracted significant attention for TE applications. SF is commonly dissolved into an aqueous solution and can be easily reconstructed into different material formats, including films, mats, hydrogels, and sponges via various fabrication techniques. These include spin coating, electrospinning, freeze drying, physical, and chemical crosslinking techniques. Furthermore, to facilitate fabrication of more complex SF-based scaffolds with high precision techniques including micro-patterning and bio-printing have recently been explored. This review introduces the physicochemical and mechanical properties of SF and looks into a range of SF-based scaffolds that have been recently developed. The typical TE applications of SF-based scaffolds including bone, cartilage, ligament, tendon, skin, wound healing, and tympanic membrane, will be highlighted and discussed, followed by future prospects and challenges needing to be addressed. Full article

(This article belongs to the Special Issue Cell-Biomaterial Interaction 2020)

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28 pages, 5303 KiB

Open AccessReview

Advanced Multi-Dimensional Cellular Models as Emerging Reality to Reproduce In Vitro the Human Body Complexity

by Giada Bassi, Maria Aurora Grimaudo, Silvia Panseri and Monica Montesi

Int. J. Mol. Sci. 2021, 22(3), 1195; https://doi.org/10.3390/ijms22031195 - 26 Jan 2021

Cited by 38 | Viewed by 7985

Abstract

A hot topic in biomedical science is the implementation of more predictive in vitro models of human tissues to significantly improve the knowledge of physiological or pathological process, drugs discovery and screening. Bidimensional (2D) culture systems still represent good high-throughput options for basic [...] Read more.

A hot topic in biomedical science is the implementation of more predictive in vitro models of human tissues to significantly improve the knowledge of physiological or pathological process, drugs discovery and screening. Bidimensional (2D) culture systems still represent good high-throughput options for basic research. Unfortunately, these systems are not able to recapitulate the in vivo three-dimensional (3D) environment of native tissues, resulting in a poor in vitro–in vivo translation. In addition, intra-species differences limited the use of animal data for predicting human responses, increasing in vivo preclinical failures and ethical concerns. Dealing with these challenges, in vitro 3D technological approaches were recently bioengineered as promising platforms able to closely capture the complexity of in vivo normal/pathological tissues. Potentially, such systems could resemble tissue-specific extracellular matrix (ECM), cell–cell and cell–ECM interactions and specific cell biological responses to mechanical and physical/chemical properties of the matrix. In this context, this review presents the state of the art of the most advanced progresses of the last years. A special attention to the emerging technologies for the development of human 3D disease-relevant and physiological models, varying from cell self-assembly (i.e., multicellular spheroids and organoids) to the use of biomaterials and microfluidic devices has been given. Full article

(This article belongs to the Special Issue Cell-Biomaterial Interaction 2020)

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19 pages, 3322 KiB

Open AccessReview

Strategies for Using Polydopamine to Induce Biomineralization of Hydroxyapatite on Implant Materials for Bone Tissue Engineering

by Neha Kaushik, Linh Nhat Nguyen, June Hyun Kim, Eun Ha Choi and Nagendra Kumar Kaushik

Int. J. Mol. Sci. 2020, 21(18), 6544; https://doi.org/10.3390/ijms21186544 - 7 Sep 2020

Cited by 51 | Viewed by 6521

Abstract

In the field of tissue engineering, there are several issues to consider when designing biomaterials for implants, including cellular interaction, good biocompatibility, and biochemical activity. Biomimetic mineralization has gained considerable attention as an emerging approach for the synthesis of biocompatible materials with complex [...] Read more.

In the field of tissue engineering, there are several issues to consider when designing biomaterials for implants, including cellular interaction, good biocompatibility, and biochemical activity. Biomimetic mineralization has gained considerable attention as an emerging approach for the synthesis of biocompatible materials with complex shapes, categorized organization, controlled shape, and size in aqueous environments. Understanding biomineralization strategies could enhance opportunities for novel biomimetic mineralization approaches. In this regard, mussel-inspired biomaterials have recently attracted many researchers due to appealing features, such as strong adhesive properties on moist surfaces, improved cell adhesion, and immobilization of bioactive molecules via catechol chemistry. This molecular designed approach has been a key point in combining new functionalities into accessible biomaterials for biomedical applications. Polydopamine (PDA) has emerged as a promising material for biomaterial functionalization, considering its simple molecular structure, independence of target materials, cell interactions for adhesion, and robust reactivity for resulting functionalization. In this review, we highlight the strategies for using PDA to induce the biomineralization of hydroxyapatite (HA) on the surface of various implant materials with good mechanical strength and corrosion resistance. We also discuss the interactions between the PDA-HA coating, and several cell types that are intricate in many biomedical applications, involving bone defect repair, bone regeneration, cell attachment, and antibacterial activity. Full article

(This article belongs to the Special Issue Cell-Biomaterial Interaction 2020)

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49 pages, 21510 KiB

Open AccessReview

Interactions of Zinc Oxide Nanostructures with Mammalian Cells: Cytotoxicity and Photocatalytic Toxicity

by Chengzhu Liao, Yuming Jin, Yuchao Li and Sie Chin Tjong

Int. J. Mol. Sci. 2020, 21(17), 6305; https://doi.org/10.3390/ijms21176305 - 31 Aug 2020

Cited by 80 | Viewed by 8660

Abstract

This article presents a state-of-the-art review and analysis of literature studies on the morphological structure, fabrication, cytotoxicity, and photocatalytic toxicity of zinc oxide nanostructures (nZnO) of mammalian cells. nZnO with different morphologies, e.g., quantum dots, nanoparticles, nanorods, and nanotetrapods are toxic to a [...] Read more.

This article presents a state-of-the-art review and analysis of literature studies on the morphological structure, fabrication, cytotoxicity, and photocatalytic toxicity of zinc oxide nanostructures (nZnO) of mammalian cells. nZnO with different morphologies, e.g., quantum dots, nanoparticles, nanorods, and nanotetrapods are toxic to a wide variety of mammalian cell lines due to in vitro cell–material interactions. Several mechanisms responsible for in vitro cytotoxicity have been proposed. These include the penetration of nZnO into the cytoplasm, generating reactive oxygen species (ROS) that degrade mitochondrial function, induce endoplasmic reticulum stress, and damage deoxyribonucleic acid (DNA), lipid, and protein molecules. Otherwise, nZnO dissolve extracellularly into zinc ions and the subsequent diffusion of ions into the cytoplasm can create ROS. Furthermore, internalization of nZnO and localization in acidic lysosomes result in their dissolution into zinc ions, producing ROS too in cytoplasm. These ROS-mediated responses induce caspase-dependent apoptosis via the activation of B-cell lymphoma 2 (Bcl2), Bcl2-associated X protein (Bax), CCAAT/enhancer-binding protein homologous protein (chop), and phosphoprotein p53 gene expressions. In vivo studies on a mouse model reveal the adverse impacts of nZnO on internal organs through different administration routes. The administration of ZnO nanoparticles into mice via intraperitoneal instillation and intravenous injection facilitates their accumulation in target organs, such as the liver, spleen, and lung. ZnO is a semiconductor with a large bandgap showing photocatalytic behavior under ultraviolet (UV) light irradiation. As such, photogenerated electron–hole pairs react with adsorbed oxygen and water molecules to produce ROS. So, the ROS-mediated selective killing for human tumor cells is beneficial for cancer treatment in photodynamic therapy. The photoinduced effects of noble metal doped nZnO for creating ROS under UV and visible light for killing cancer cells are also addressed. Full article

(This article belongs to the Special Issue Cell-Biomaterial Interaction 2020)

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