International Journal of Molecular Sciences

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11 pages, 1916 KiB

Open AccessArticle

Purification of Boron Nitride Nanotubes Enhances Biological Application Properties

by Soul-Hee Lee, Myung Jong Kim, Seokhoon Ahn and Byumseok Koh

Int. J. Mol. Sci. 2020, 21(4), 1529; https://doi.org/10.3390/ijms21041529 - 24 Feb 2020

Cited by 31 | Viewed by 5096

Abstract

Commercially available boron nitride nanotubes (BNNTs) and their purified form (pBNNTs) were dispersed in aqueous solutions with various dispersants, and their cytotoxicity and drug encapsulation capacity were monitored. Our data suggest that pBNNTs showed an average increase in dispersibility of 37.3% in aqueous [...] Read more.

Commercially available boron nitride nanotubes (BNNTs) and their purified form (pBNNTs) were dispersed in aqueous solutions with various dispersants, and their cytotoxicity and drug encapsulation capacity were monitored. Our data suggest that pBNNTs showed an average increase in dispersibility of 37.3% in aqueous solution in the presence of 10 different dispersants. In addition, 100 μg of pBNNTs induced an average decrease in cytotoxicity of 27.4% compared to same amount of BNNTs in normal cell lines. The same amount of pBNNTs can encapsulate 10.4-fold more drug (camptothecin) compared to BNNTs. These data suggest that the purification of BNNTs improves several of their properties, which can be applied to biological experiments and are thus essential in the biological application of BNNTs. Full article

(This article belongs to the Special Issue Cell-Biomaterial Interaction 2019)

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15 pages, 4193 KiB

Open AccessArticle

Effects of Encapsulated Cells on the Physical–Mechanical Properties and Microstructure of Gelatin Methacrylate Hydrogels

by Srikumar Krishnamoorthy, Behnam Noorani and Changxue Xu

Int. J. Mol. Sci. 2019, 20(20), 5061; https://doi.org/10.3390/ijms20205061 - 12 Oct 2019

Cited by 65 | Viewed by 8996

Abstract

Gelatin methacrylate (GelMA) has been gaining popularity in recent years as a photo-crosslinkable biomaterial widely used in a variety of bioprinting and tissue engineering applications. Several studies have established the effects of process-based and material-based parameters on the physical–mechanical properties and microstructure of [...] Read more.

Gelatin methacrylate (GelMA) has been gaining popularity in recent years as a photo-crosslinkable biomaterial widely used in a variety of bioprinting and tissue engineering applications. Several studies have established the effects of process-based and material-based parameters on the physical–mechanical properties and microstructure of GelMA hydrogels. However, the effect of encapsulated cells on the physical–mechanical properties and microstructure of GelMA hydrogels has not been fully understood. In this study, 3T3 fibroblasts were encapsulated at different cell densities within the GelMA hydrogels and incubated over 96 h. The effects of encapsulated cells were investigated in terms of mechanical properties (tensile modulus and strength), physical properties (swelling and degradation), and microstructure (pore size). Cell viability was also evaluated to confirm that most cells were alive during the incubation. It was found that with an increase in cell density, the mechanical properties decreased, while the degradation and the pore size increased. Full article

(This article belongs to the Special Issue Cell-Biomaterial Interaction 2019)

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14 pages, 3570 KiB

Open AccessArticle

Solid Nanocrystals of Rebamipide Promote Recovery from Indomethacin-Induced Gastrointestinal Bleeding

by Noriaki Nagai, Ryusuke Sakamoto, Seiji Yamamoto, Saori Deguchi, Hiroko Otake and Tadatoshi Tanino

Int. J. Mol. Sci. 2019, 20(20), 4990; https://doi.org/10.3390/ijms20204990 - 9 Oct 2019

Cited by 4 | Viewed by 3354

Abstract

Indomethacin (IMC)-induced gastrointestinal (GI) injuries are more common in rheumatoid arthritis (RA) patients than in other IMC users, and the overexpression of nitric oxide (NO) via inducible NO synthase (iNOS) is related to the seriousness of IMC-induced GI injuries. However, sufficient strategies to [...] Read more.

Indomethacin (IMC)-induced gastrointestinal (GI) injuries are more common in rheumatoid arthritis (RA) patients than in other IMC users, and the overexpression of nitric oxide (NO) via inducible NO synthase (iNOS) is related to the seriousness of IMC-induced GI injuries. However, sufficient strategies to prevent IMC-induced GI injuries have not yet been established. In this study, we designed dispersions of rebamipide (RBM) solid nanocrystals (particle size: 30–190 nm) by a bead mill method (RBM-NDs), and investigated whether the oral administration of RBM-NDs is useful to prevent IMC-induced GI injuries. The RBM nanocrystals were spherical and had a solubility 4.71-fold greater than dispersions of traditional RBM powder (RBM-TDs). In addition, the RBM-NDs were stable for 1 month after preparation. The RBM contents in the stomach, jejunum, and ileum of rats orally administered RBM-NDs were significantly higher than in rats administered RBM-TDs. Moreover, the oral administration of RBM-NDs decreased the NO levels via iNOS and area of the GI lesions in IMC-stimulated RA (adjuvant-induced arthritis rat) rats in comparison with the oral administration of RBM-TDs. Thus, we show that the oral administration of RBM-NDs provides a high drug supply to the GI mucosa, resulting in a therapeutic effect on IMC-induced GI injuries. Solid nanocrystalline RBM preparations may offer effective therapy for RA patients. Full article

(This article belongs to the Special Issue Cell-Biomaterial Interaction 2019)

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11 pages, 3864 KiB

Open AccessArticle

Hydrogel-Mediated DOX⋅HCl/PTX Delivery System for Breast Cancer Therapy

by Hoon Hyun, Young Bum Yoo, So Yeon Kim, Hyun Sun Ko, Heung Jae Chun and Dae Hyeok Yang

Int. J. Mol. Sci. 2019, 20(19), 4671; https://doi.org/10.3390/ijms20194671 - 20 Sep 2019

Cited by 18 | Viewed by 3540

Abstract

We used a hydrogel-mediated dual drug delivery approach, based on an injectable glycol chitosan (GC) hydrogel, doxorubicin hydrochloride (DOX⋅HCl), and a complex of beta-cyclodextrin (β-CD) and paclitaxel (PTX) (GDCP) for breast cancer therapy in vitro and in vivo. The hydrogel was swollen over [...] Read more.

We used a hydrogel-mediated dual drug delivery approach, based on an injectable glycol chitosan (GC) hydrogel, doxorubicin hydrochloride (DOX⋅HCl), and a complex of beta-cyclodextrin (β-CD) and paclitaxel (PTX) (GDCP) for breast cancer therapy in vitro and in vivo. The hydrogel was swollen over 3 days and remained so thereafter. After an initial burst period of 7 hours, the two drugs were released in a sustained manner for 7 days. The in vitro cell viability test showed that GDCP had a better anticancer effect than well plate and DOX⋅HCl/PTX (DP). In addition, the in vivo tests, which evaluated the anticancer effect, systemic toxicity, and histology, proved the feasibility of GDCP as a clinical therapy for breast cancer. Full article

(This article belongs to the Special Issue Cell-Biomaterial Interaction 2019)

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11 pages, 4329 KiB

Open AccessArticle

A New Approach for Glyco-Functionalization of Collagen-Based Biomaterials

by Ines Figuereido, Alice Paiotta, Roberta Dal Magro, Francesca Tinelli, Roberta Corti, Francesca Re, Valeria Cassina, Enrico Caneva, Francesco Nicotra and Laura Russo

Int. J. Mol. Sci. 2019, 20(7), 1747; https://doi.org/10.3390/ijms20071747 - 9 Apr 2019

Cited by 8 | Viewed by 3952

Abstract

The cell microenvironment plays a pivotal role in mediating cell adhesion, survival, and proliferation in physiological and pathological states. The relevance of extracellular matrix (ECM) proteins in cell fate control is an important issue to take into consideration for both tissue engineering and [...] Read more.

The cell microenvironment plays a pivotal role in mediating cell adhesion, survival, and proliferation in physiological and pathological states. The relevance of extracellular matrix (ECM) proteins in cell fate control is an important issue to take into consideration for both tissue engineering and cell biology studies. The glycosylation of ECM proteins remains, however, largely unexplored. In order to investigate the physio-pathological effects of differential ECM glycosylation, the design of affordable chemoselective methods for ECM components glycosylation is desirable. We will describe a new chemoselective glycosylation approach exploitable in aqueous media and on non-protected substrates, allowing rapid access to glyco-functionalized biomaterials. Full article

(This article belongs to the Special Issue Cell-Biomaterial Interaction 2019)

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18 pages, 3830 KiB

Open AccessArticle

Effect of Polymer Phase Transition Behavior on Temperature-Responsive Polymer-Modified Liposomes for siRNA Transfection

by Kenichi Nagase, Momoko Hasegawa, Eri Ayano, Yoshie Maitani and Hideko Kanazawa

Int. J. Mol. Sci. 2019, 20(2), 430; https://doi.org/10.3390/ijms20020430 - 19 Jan 2019

Cited by 50 | Viewed by 5895

Abstract

Small interfering RNAs (siRNAs) have been attracting significant attention owing to their gene silencing properties, which can be utilized to treat intractable diseases. In this study, two temperature-responsive liposomal siRNA carriers were prepared by modifying liposomes with different polymers—poly(N-isopropylacrylamide-co- [...] Read more.

Small interfering RNAs (siRNAs) have been attracting significant attention owing to their gene silencing properties, which can be utilized to treat intractable diseases. In this study, two temperature-responsive liposomal siRNA carriers were prepared by modifying liposomes with different polymers—poly(N-isopropylacrylamide-co-N,N-dimethylaminopropyl acrylamide) (P(NIPAAm-co-DMAPAAm)) and poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide) P(NIPAAm-co-DMAAm). The phase transition of P(NIPAAm-co-DMAPAAm) was sharper than that of P(NIPAAm-co-DMAAm), which is attributed to the lower co-monomer content. The temperature dependent fixed aqueous layer thickness (FALT) of the prepared liposomes indicated that modifying liposomes with P(NIPAAm-co-DMAPAAm) led to a significant change in the thickness of the fixed aqueous monolayer between 37 °C and 42 °C; while P(NIPAAm-co-DMAAm) modification led to FALT changes over a broader temperature range. The temperature-responsive liposomes exhibited cellular uptake at 42 °C, but were not taken up by cells at 37 °C. This is likely because the thermoresponsive hydrophilic/hydrophobic changes at the liposome surface induced temperature-responsive cellular uptake. Additionally, siRNA transfection of cells for the prevention of luciferase and vascular endothelial growth factor (VEGF) expression was modulated by external temperature changes. P(NIPAAm-co-DMAPAAm) modified liposomes in particular exhibited effective siRNA transfection properties with low cytotoxicity compared with P(NIPAAm-co-DMAAm) modified analogues. These results indicated that the prepared temperature-responsive liposomes could be used as effective siRNA carriers whose transfection properties can be modulated by temperature. Full article

(This article belongs to the Special Issue Cell-Biomaterial Interaction 2019)

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Review

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28 pages, 2317 KiB

Open AccessReview

Recent Trends in Decellularized Extracellular Matrix Bioinks for 3D Printing: An Updated Review

by Kevin Dzobo, Keolebogile Shirley Caroline M. Motaung and Adetola Adesida

Int. J. Mol. Sci. 2019, 20(18), 4628; https://doi.org/10.3390/ijms20184628 - 18 Sep 2019

Cited by 168 | Viewed by 12068

Abstract

The promise of regenerative medicine and tissue engineering is founded on the ability to regenerate diseased or damaged tissues and organs into functional tissues and organs or the creation of new tissues and organs altogether. In theory, damaged and diseased tissues and organs [...] Read more.

The promise of regenerative medicine and tissue engineering is founded on the ability to regenerate diseased or damaged tissues and organs into functional tissues and organs or the creation of new tissues and organs altogether. In theory, damaged and diseased tissues and organs can be regenerated or created using different configurations and combinations of extracellular matrix (ECM), cells, and inductive biomolecules. Regenerative medicine and tissue engineering can allow the improvement of patients’ quality of life through availing novel treatment options. The coupling of regenerative medicine and tissue engineering with 3D printing, big data, and computational algorithms is revolutionizing the treatment of patients in a huge way. 3D bioprinting allows the proper placement of cells and ECMs, allowing the recapitulation of native microenvironments of tissues and organs. 3D bioprinting utilizes different bioinks made up of different formulations of ECM/biomaterials, biomolecules, and even cells. The choice of the bioink used during 3D bioprinting is very important as properties such as printability, compatibility, and physical strength influence the final construct printed. The extracellular matrix (ECM) provides both physical and mechanical microenvironment needed by cells to survive and proliferate. Decellularized ECM bioink contains biochemical cues from the original native ECM and also the right proportions of ECM proteins. Different techniques and characterization methods are used to derive bioinks from several tissues and organs and to evaluate their quality. This review discusses the uses of decellularized ECM bioinks and argues that they represent the most biomimetic bioinks available. In addition, we briefly discuss some polymer-based bioinks utilized in 3D bioprinting. Full article

(This article belongs to the Special Issue Cell-Biomaterial Interaction 2019)

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33 pages, 3708 KiB

Open AccessReview

Molecular-Level Interactions between Engineered Materials and Cells

by Yoon-ha Jang, Xuelin Jin, Prabakaran Shankar, Jung Heon Lee, Kyubong Jo and Kwang-il Lim

Int. J. Mol. Sci. 2019, 20(17), 4142; https://doi.org/10.3390/ijms20174142 - 25 Aug 2019

Cited by 13 | Viewed by 6221

Abstract

Various recent experimental observations indicate that growing cells on engineered materials can alter their physiology, function, and fate. This finding suggests that better molecular-level understanding of the interactions between cells and materials may guide the design and construction of sophisticated artificial substrates, potentially [...] Read more.

Various recent experimental observations indicate that growing cells on engineered materials can alter their physiology, function, and fate. This finding suggests that better molecular-level understanding of the interactions between cells and materials may guide the design and construction of sophisticated artificial substrates, potentially enabling control of cells for use in various biomedical applications. In this review, we introduce recent research results that shed light on molecular events and mechanisms involved in the interactions between cells and materials. We discuss the development of materials with distinct physical, chemical, and biological features, cellular sensing of the engineered materials, transfer of the sensing information to the cell nucleus, subsequent changes in physical and chemical states of genomic DNA, and finally the resulting cellular behavior changes. Ongoing efforts to advance materials engineering and the cell–material interface will eventually expand the cell-based applications in therapies and tissue regenerations. Full article

(This article belongs to the Special Issue Cell-Biomaterial Interaction 2019)

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18 pages, 496 KiB

Open AccessReview

Functional Protein-Based Bioinspired Nanomaterials: From Coupled Proteins, Synthetic Approaches, Nanostructures to Applications

by Dong Zhang and Yi Wang

Int. J. Mol. Sci. 2019, 20(12), 3054; https://doi.org/10.3390/ijms20123054 - 22 Jun 2019

Cited by 14 | Viewed by 4855

Abstract

Protein-based bioinspired nanomaterials (PBNs) combines the advantage of the size, shape, and surface chemistry of nanomaterials, the morphology and functions of natural materials, and the physical and chemical properties of various proteins. Recently, there are many exciting developments on biomimetic nanomaterials using proteins [...] Read more.

Protein-based bioinspired nanomaterials (PBNs) combines the advantage of the size, shape, and surface chemistry of nanomaterials, the morphology and functions of natural materials, and the physical and chemical properties of various proteins. Recently, there are many exciting developments on biomimetic nanomaterials using proteins for different applications including, tissue engineering, drug delivery, diagnosis and therapy, smart materials and structures, and water collection and separation. Protein-based biomaterials with high biocompatibility and biodegradability could be modified to obtain the healing effects of natural organisms after injury by mimicking the extracellular matrix. For cancer and other diseases that are difficult to cure now, new therapeutic methods involving different kinds of biomaterials are studied. The nanomaterials with surface modification, which can achieve high drug loading, can be used as drug carriers to enhance target and trigger deliveries. For environment protection and the sustainability of the world, protein-based nanomaterials are also applied for water treatment. A wide range of contaminants from natural water source, such as organic dyes, oil substances, and multiple heavy ions, could be absorbed by protein-based nanomaterials. This review summarizes the formation and application of functional PBNs, and the details of their nanostructures, the proteins involved, and the synthetic approaches are addressed. Full article

(This article belongs to the Special Issue Cell-Biomaterial Interaction 2019)

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16 pages, 4718 KiB

Open AccessReview

From Acellular Matrices to Smart Polymers: Degradable Scaffolds that are Transforming the Shape of Urethral Tissue Engineering

by Tariq O. Abbas, Huseyin C. Yalcin and Cristian P. Pennisi

Int. J. Mol. Sci. 2019, 20(7), 1763; https://doi.org/10.3390/ijms20071763 - 10 Apr 2019

Cited by 30 | Viewed by 7109

Abstract

Several congenital and acquired conditions may result in severe narrowing of the urethra in men, which represent an ongoing surgical challenge and a significant burden on both health and quality of life. In the field of urethral reconstruction, tissue engineering has emerged as [...] Read more.

Several congenital and acquired conditions may result in severe narrowing of the urethra in men, which represent an ongoing surgical challenge and a significant burden on both health and quality of life. In the field of urethral reconstruction, tissue engineering has emerged as a promising alternative to overcome some of the limitations associated with autologous tissue grafts. In this direction, preclinical as well as clinical studies, have shown that degradable scaffolds are able to restore the normal urethral architecture, supporting neo-vascularization and stratification of the tissue. While a wide variety of degradable biomaterials are under scrutiny, such as decellularized matrices, natural, and synthetic polymers, the search for scaffold materials that could fulfill the clinical performance requirements continues. In this article, we discuss the design requirements of the scaffold that appear to be crucial to better resemble the structural, physical, and biological properties of the native urethra and are expected to support an adequate recovery of the urethral function. In this context, we review the biological performance of the degradable polymers currently applied for urethral reconstruction and outline the perspectives on novel functional polymers, which could find application in the design of customized urethral constructs. Full article

(This article belongs to the Special Issue Cell-Biomaterial Interaction 2019)

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42 pages, 1344 KiB

Open AccessReview

Biomaterials: Foreign Bodies or Tuners for the Immune Response?

by Erminia Mariani, Gina Lisignoli, Rosa Maria Borzì and Lia Pulsatelli

Int. J. Mol. Sci. 2019, 20(3), 636; https://doi.org/10.3390/ijms20030636 - 1 Feb 2019

Cited by 459 | Viewed by 16566

Abstract

The perspectives of regenerative medicine are still severely hampered by the host response to biomaterial implantation, despite the robustness of technologies that hold the promise to recover the functionality of damaged organs and tissues. In this scenario, the cellular and molecular events that [...] Read more.

The perspectives of regenerative medicine are still severely hampered by the host response to biomaterial implantation, despite the robustness of technologies that hold the promise to recover the functionality of damaged organs and tissues. In this scenario, the cellular and molecular events that decide on implant success and tissue regeneration are played at the interface between the foreign body and the host inflammation, determined by innate and adaptive immune responses. To avoid adverse events, rather than the use of inert scaffolds, current state of the art points to the use of immunomodulatory biomaterials and their knowledge-based use to reduce neutrophil activation, and optimize M1 to M2 macrophage polarization, Th1 to Th2 lymphocyte switch, and Treg induction. Despite the fact that the field is still evolving and much remains to be accomplished, recent research breakthroughs have provided a broader insight on the correct choice of biomaterial physicochemical modifications to tune the reaction of the host immune system to implanted biomaterial and to favor integration and healing. Full article

(This article belongs to the Special Issue Cell-Biomaterial Interaction 2019)

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17 pages, 3169 KiB

Open AccessReview

Innovative Biomaterials for Bone Regrowth

by Maria Rosa Iaquinta, Elisa Mazzoni, Marco Manfrini, Antonio D’Agostino, Lorenzo Trevisiol, Riccardo Nocini, Leonardo Trombelli, Giovanni Barbanti-Brodano, Fernanda Martini and Mauro Tognon

Int. J. Mol. Sci. 2019, 20(3), 618; https://doi.org/10.3390/ijms20030618 - 31 Jan 2019

Cited by 119 | Viewed by 9083

Abstract

The regenerative medicine, a new discipline that merges biological sciences and the fundamental of engineering to develop biological substitutes, has greatly benefited from recent advances in the material engineering and the role of stem cells in tissue regeneration. Regenerative medicine strategies, involving the [...] Read more.

The regenerative medicine, a new discipline that merges biological sciences and the fundamental of engineering to develop biological substitutes, has greatly benefited from recent advances in the material engineering and the role of stem cells in tissue regeneration. Regenerative medicine strategies, involving the combination of biomaterials/scaffolds, cells, and bioactive agents, have been of great interest especially for the repair of damaged bone and bone regrowth. In the last few years, the life expectancy of our population has progressively increased. Aging has highlighted the need for intervention on human bone with biocompatible materials that show high performance for the regeneration of the bone, efficiently and in a short time. In this review, the different aspects of tissue engineering applied to bone engineering were taken into consideration. The first part of this review introduces the bone cellular biology/molecular genetics. Data on biomaterials, stem cells, and specific growth factors for the bone regrowth are reported in this review. Full article

(This article belongs to the Special Issue Cell-Biomaterial Interaction 2019)

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16 pages, 948 KiB

Open AccessReview

Exploiting PLGA-Based Biocompatible Nanoparticles for Next-Generation Tolerogenic Vaccines against Autoimmune Disease

by Giuseppe Cappellano, Cristoforo Comi, Annalisa Chiocchetti and Umberto Dianzani

Int. J. Mol. Sci. 2019, 20(1), 204; https://doi.org/10.3390/ijms20010204 - 8 Jan 2019

Cited by 96 | Viewed by 7986

Abstract

Tolerogenic vaccines are aimed at inhibiting antigen-specific immune responses. Antigen-loaded nanoparticles (NPs) have been recently emerged as ideal tools for tolerogenic vaccination because their composition, size, and capability of loading immunomodulatory molecules can be readily exploited to induce peripheral tolerance. Among polymeric NPs, [...] Read more.

Tolerogenic vaccines are aimed at inhibiting antigen-specific immune responses. Antigen-loaded nanoparticles (NPs) have been recently emerged as ideal tools for tolerogenic vaccination because their composition, size, and capability of loading immunomodulatory molecules can be readily exploited to induce peripheral tolerance. Among polymeric NPs, poly(lactic-co-glycolic acid) (PLGA) NPs have the advantage of currently holding approval for several applications in drug delivery, diagnostics, and other clinical uses by the Food and Drug Administration (FDA). PLGA-NPs are non-toxic and display excellent biocompatibility and biodegradability properties. Moreover, surface functionalization may improve their interaction with biological materials, thereby optimizing targeting and performance. PLGA-NPs are the most extensively studied in pre-clinical model in the field of tolerogenic vaccination. Thus, this review describes their potential applications in the treatment of autoimmune diseases. Full article

(This article belongs to the Special Issue Cell-Biomaterial Interaction 2019)

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