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Nanomaterials for Tissue Engineering Applications

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Materials Science".

Deadline for manuscript submissions: closed (5 September 2020) | Viewed by 37223

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Prof. Dr. Jyh-Ping Chen

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Department of Chemical and Materials Engineering, Chang Gung University, Taoyuan 33302, Taiwan
Interests: drug delivery; tissue engineering; nanobiotechnology
Special Issues, Collections and Topics in MDPI journals

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Dear Colleagues,

As nanotechnology applications in medicine have attracted worldwide interest, nanotechnological approaches to tissue engineering could also lead to many innovative solutions for repairing tissue damage. Employing three-dimensional scaffolds in tissue engineering is a key element among recent advancements in tissue engineering and biomaterial research. As scaffold materials, nanomaterials have gained popularity due to their many advantages over conventional techniques for tissue repair. Nanomaterials have shown superior performance over conventional materials for tissue engineering applications, such as in bone regeneration, cartilage repair, tendon/ligament regeneration, vascular tissue engineering, skin regeneration, nerve tissue engineering, corneal regeneration, etc. The ability of nanomaterials to mimic the native extracellular matrix and their ability to aid in cellular activity make these materials suitable candidates for scaffold fabrication. For instance, the high surface-to-volume ratio of nanofibers provides good cellular adhesion and rapid cell attachment on the material's surface. Interconnected pores within nanofiber membranes could facilitate nutrient and oxygen transfer. Indeed, recent nanotechnological developments have offered opportunities to greatly improve the properties of tissue-engineered scaffolds, and nanoscience approaches are suggesting some novel substitutes that could more precisely mimic the in vivo conditions of natural tissues.

This Special Issue will therefore focus on various tissue engineering approaches for the regeneration of different tissues/organs, with an emphasis on nanomaterials used in different aspects of tissue engineering and their role in tissue regeneration.

Prof. Dr. Jyh-Ping Chen
Guest Editor

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Keywords

tissue engineering
scaffolds
biodegradable materials
nanostructured biomaterials
regenerative medicine
bone
cartilage repair
tendon
skin

Related Special Issue

Nanomaterials for Tissue Engineering Applications 3.0 in International Journal of Molecular Sciences (3 articles)

Published Papers (10 papers)

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Research

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13 pages, 5054 KiB

Open AccessArticle

Investigation of Bone Growth in Additive-Manufactured Pedicle Screw Implant by Using Ti-6Al-4V and Bioactive Glass Powder Composite

by Tu-Ngoc Lam, Minh-Giam Trinh, Chih-Chieh Huang, Pei-Ching Kung, Wei-Chin Huang, Wei Chang, Lia Amalia, Hsu-Hsuan Chin, Nien-Ti Tsou, Shao-Ju Shih, San-Yuan Chen, Chun-Chieh Wang, Pei-I Tsai, Meng-Huang Wu and E-Wen Huang

Int. J. Mol. Sci. 2020, 21(20), 7438; https://doi.org/10.3390/ijms21207438 - 09 Oct 2020

Cited by 8 | Viewed by 3755

Abstract

In this study, we optimized the geometry and composition of additive-manufactured pedicle screws. Metal powders of titanium-aluminum-vanadium (Ti-6Al-4V) were mixed with reactive glass-ceramic biomaterials of bioactive glass (BG) powders. To optimize the geometry of pedicle screws, we applied a novel numerical approach to proposing the optimal shape of the healing chamber to promote biological healing. We examined the geometry and composition effects of pedicle screw implants on the interfacial autologous bone attachment and bone graft incorporation through in vivo studies. The addition of an optimal amount of BG to Ti-6Al-4V leads to a lower elastic modulus of the ceramic-metal composite material, effectively reducing the stress-shielding effects. Pedicle screw implants with optimal shape design and made of the composite material of Ti-6Al-4V doped with BG fabricated through additive manufacturing exhibit greater osseointegration and a more rapid bone volume fraction during the fracture healing process 120 days after implantation, per in vivo studies. Full article

(This article belongs to the Special Issue Nanomaterials for Tissue Engineering Applications)

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25 pages, 4559 KiB

Open AccessArticle

Immobilization of BMP-2 and VEGF within Multilayered Polydopamine-Coated Scaffolds and the Resulting Osteogenic and Angiogenic Synergy of Co-Cultured Human Mesenchymal Stem Cells and Human Endothelial Progenitor Cells

by Maria Godoy-Gallardo, Núria Portolés-Gil, Ana M. López-Periago, Concepción Domingo and Leticia Hosta-Rigau

Int. J. Mol. Sci. 2020, 21(17), 6418; https://doi.org/10.3390/ijms21176418 - 03 Sep 2020

Cited by 27 | Viewed by 3942

Abstract

We have previously reported the fabrication of a polycaprolactone and hydroxyapatite composite scaffold incorporating growth factors to be used for bone regeneration. Two growth factors were incorporated employing a multilayered coating based on polydopamine (PDA). In particular, Bone morphogenetic protein-2 (BMP-2) was bound onto the inner PDA layer while vascular endothelial growth factor (VEGF) was immobilized onto the outer one. Herein, the in vitro release of both growth factors is evaluated. A fastest VEGF delivery followed by a slow and more sustained release of BMP-2 was demonstrated, thus fitting the needs for bone tissue engineering applications. Due to the relevance of the crosstalk between bone-promoting and vessel-forming cells during bone healing, the functionalized scaffolds are further assessed on a co-culture setup of human mesenchymal stem cells and human endothelial progenitor cells. Osteogenic and angiogenic gene expression analysis indicates a synergistic effect between the growth factor-loaded scaffolds and the co-culture conditions. Taken together, these results indicate that the developed scaffolds hold great potential as an efficient platform for bone-tissue applications. Full article

(This article belongs to the Special Issue Nanomaterials for Tissue Engineering Applications)

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27 pages, 8543 KiB

Open AccessArticle

Frame Coating of Single-Walled Carbon Nanotubes in Collagen on PET Fibers for Artificial Joint Ligaments

by Alexander Yu. Gerasimenko, Natalia N. Zhurbina, Nadezhda G. Cherepanova, Anna E. Semak, Vadim V. Zar, Yulia O. Fedorova, Elena M. Eganova, Alexander A. Pavlov, Dmitry V. Telyshev, Sergey V. Selishchev and Olga E. Glukhova

Int. J. Mol. Sci. 2020, 21(17), 6163; https://doi.org/10.3390/ijms21176163 - 26 Aug 2020

Cited by 16 | Viewed by 4422

Abstract

The coating formation technique for artificial knee ligaments was proposed, which provided tight fixation of ligaments of polyethylene terephthalate (PET) fibers as a result of the healing of the bone channel in the short-term period after implantation. The coating is a frame structure of single-walled carbon nanotubes (SWCNT) in a collagen matrix, which is formed by layer-by-layer solidification of an aqueous dispersion of SWCNT with collagen during spin coating and controlled irradiation with IR radiation. Quantum mechanical method SCC DFTB, with a self-consistent charge, was used. It is based on the density functional theory and the tight-binding approximation. The method established the optimal temperature and time for the formation of the equilibrium configurations of the SWCNT/collagen type II complexes to ensure maximum binding energies between the nanotube and the collagen. The highest binding energies were observed in complexes with SWCNT nanometer diameter in comparison with subnanometer SWCNT. The coating had a porous structure—pore size was 0.5—6 μm. The process of reducing the mass and volume of the coating with the initial biodegradation of collagen after contact with blood plasma was demonstrated. This is proved by exceeding the intensity of the SWCNT peaks G and D after contact with the blood serum in the Raman spectrum and by decreasing the intensity of the main collagen bands in the SWCNT/collagen complex frame coating. The number of pores and their size increased to 20 μm. The modification of the PET tape with the SWCNT/collagen coating allowed to increase its hydrophilicity by 1.7 times compared to the original PET fibers and by 1.3 times compared to the collagen coating. A reduced hemolysis level of the PET tape coated with SWCNT/collagen was achieved. The SWCNT/collagen coating provided 2.2 times less hemolysis than an uncoated PET implant. MicroCT showed the effective formation of new bone and dense connective tissue around the implant. A decrease in channel diameter from 2.5 to 1.7 mm was detected at three and, especially, six months after implantation of a PET tape with SWCNT/collagen coating. MicroCT allowed us to identify areas for histological sections, which demonstrated the favorable interaction of the PET tape with the surrounding tissues. In the case of using the PET tape coated with SWCNT/collagen, more active growth of connective tissue with mature collagen fibers in the area of implantation was observed than in the case of only collagen coating. The stimulating effect of SWCNT/collagen on the formation of bone trabeculae around and inside the PET tape was evident in three and six months after implantation. Thus, a PET tape with SWCNT/collagen coating has osteoconductivity as well as a high level of hydrophilicity and hemocompatibility. Full article

(This article belongs to the Special Issue Nanomaterials for Tissue Engineering Applications)

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25 pages, 6541 KiB

Open AccessArticle

Nanoparticles and Colloidal Hydrogels of Chitosan–Caseinate Polyelectrolyte Complexes for Drug-Controlled Release Applications

by Aastha Lall, Arnaud Kamdem Tamo, Ingo Doench, Laurent David, Paula Nunes de Oliveira, Christian Gorzelanny and Anayancy Osorio-Madrazo

Int. J. Mol. Sci. 2020, 21(16), 5602; https://doi.org/10.3390/ijms21165602 - 05 Aug 2020

Cited by 36 | Viewed by 4506

Abstract

Chitosan–caseinate nanoparticles were synthesized by polyelectrolyte complex (PEC) formation. Caseinate is an anionic micellar nanocolloid in aqueous solutions, which association with the polycationic chitosan yielded polyelectrolyte complexes with caseinate cores surrounded by a chitosan corona. The pre-structuration of caseinate micelles facilitates the formation of natural polyelectrolyte nanoparticles with good stability and sizes around 200 nm. Such natural nanoparticles can be loaded with molecules for applications in drug-controlled release. In the nanoparticles processing, parameters such as the chitosan degree of acetylation (DA) and molecular weight, order of addition of the polyelectrolytes chitosan (polycation) and caseinate (polyanion), and added weight ratio of polycation:polyanion were varied, which were shown to influence the structure of the polyelectrolyte association, the nanoparticle size and zeta potential. Attenuated total reflection-Fourier transform infrared (ATR-FTIR) analyses revealed the chemical structure of hydrogel colloidal systems consisting of nanoparticles that contain chitosan and caseinate. Transmission electron microscopy (TEM) allowed further characterization of the spherical morphology of the nanoparticles. Furtherly, insulin was chosen as a model drug to study the application of the nanoparticles as a safe biodegradable nanocarrier system for drug-controlled release. An insulin entrapment efficiency of 75% was achieved in the chitosan-caseinate nanoparticles. Full article

(This article belongs to the Special Issue Nanomaterials for Tissue Engineering Applications)

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12 pages, 3430 KiB

Open AccessArticle

Preliminary In Vitro Evaluation of Chitosan–Graphene Oxide Scaffolds on Osteoblastic Adhesion, Proliferation, and Early Differentiation

by Sonia How Ming Wong, Siew Shee Lim, Timm Joyce Tiong, Pau Loke Show, Hayyiratul Fatimah Mohd Zaid and Hwei-San Loh

Int. J. Mol. Sci. 2020, 21(15), 5202; https://doi.org/10.3390/ijms21155202 - 22 Jul 2020

Cited by 16 | Viewed by 2833

Abstract

An ideal scaffold should be biocompatible, having appropriate microstructure, excellent mechanical strength yet degrades. Chitosan exhibits most of these exceptional properties, but it is always associated with sub-optimal cytocompatibility. This study aimed to incorporate graphene oxide at wt % of 0, 2, 4, and 6 into chitosan matrix via direct blending of chitosan solution and graphene oxide, freezing, and freeze drying. Cell fixation, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide, alkaline phosphatase colorimetric assays were conducted to assess cell adhesion, proliferation, and early differentiation of MG63 on chitosan–graphene oxide scaffolds respectively. The presence of alkaline phosphatase, an early osteoblast differentiation marker, was further detected in chitosan–graphene oxide scaffolds using western blot. These results strongly supported that chitosan scaffolds loaded with graphene oxide at 2 wt % mediated cell adhesion, proliferation, and early differentiation due to the presence of oxygen-containing functional groups of graphene oxide. Therefore, chitosan scaffolds loaded with graphene oxide at 2 wt % showed the potential to be developed into functional bone scaffolds. Full article

(This article belongs to the Special Issue Nanomaterials for Tissue Engineering Applications)

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18 pages, 3243 KiB

Open AccessArticle

New Insight into Natural Extracellular Matrix: Genipin Cross-Linked Adipose-Derived Stem Cell Extracellular Matrix Gel for Tissue Engineering

by Batzaya Nyambat, Yankuba B. Manga, Chih-Hwa Chen, Uuganbayar Gankhuyag, Andi Pratomo WP, Mantosh Kumar Satapathy and Er-Yuan Chuang

Int. J. Mol. Sci. 2020, 21(14), 4864; https://doi.org/10.3390/ijms21144864 - 09 Jul 2020

Cited by 25 | Viewed by 4559

Abstract

The cell-derived extracellular matrix (ECM) is associated with a lower risk of pathogen transfer, and it possesses an ideal niche with growth factors and complex fibrillar proteins for cell attachment and growth. However, the cell-derived ECM is found to have poor biomechanical properties, and processing of cell-derived ECM into gels is scarcely studied. The gel provides platforms for three-dimensional cell culture, as well as injectable biomaterials, which could be delivered via a minimally invasive procedure. Thus, in this study, an adipose-derived stem cell (ADSC)-derived ECM gel was developed and cross-linked by genipin to address the aforementioned issue. The genipin cross-linked ADSC ECM gel was fabricated via several steps, including rabbit ADSC culture, cell sheets, decellularization, freeze–thawing, enzymatic digestion, neutralization of pH, and cross-linking. The physicochemical characteristics and cytocompatibility of the gel were evaluated. The results demonstrated that the genipin cross-linking could significantly enhance the mechanical properties of the ADSC ECM gel. Furthermore, the ADSC ECM was found to contain collagen, fibronectin, biglycan, and transforming growth factor (TGF)-β1, which could substantially maintain ADSC, skin, and ligament fibroblast cell proliferation. This cell-derived natural material could be suitable for future regenerative medicine and tissue engineering application. Full article

(This article belongs to the Special Issue Nanomaterials for Tissue Engineering Applications)

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14 pages, 2786 KiB

Open AccessArticle

A Microarray Screening Platform with an Experimental Conditions Gradient Generator for the High-Throughput Synthesis of Micro/Nanosized Calcium Phosphates

by Xiaoyu Li, Zhifeng Shi, Lei Liu, Guanglin Zhu, Jianhua Zhou, Xuetao Shi and Yingjun Wang

Int. J. Mol. Sci. 2020, 21(11), 3939; https://doi.org/10.3390/ijms21113939 - 30 May 2020

Viewed by 1961

Abstract

Calcium phosphates (CaP) represent an impressive kind of biomedical material due to their excellent biocompatibility, bioactivity, and biodegradability. Their morphology and structure highly influence their properties and applications. Whilst great progress has been made in research on biomedical materials, there is still a need to develop a method that can rapidly synthesize and screen micro/nanosized biomedical materials. Here, we utilized a microarray screening platform that could provide the high-throughput synthesis of biomedical materials and screen the vital reaction conditions. With this screening platform, 9 × 9 sets of parallel experiments could be conducted simultaneously with one- or two-dimensions of key reaction condition gradients. We used this platform to establish a one-dimensional gradient of the pH and citrate concentration and a two-dimensional gradient of both the Ca/P ratio and pH to synthesize CaP particles with various morphologies. This screening platform also shows the potential to be extended to other reaction systems for rapid high-throughput screening. Full article

(This article belongs to the Special Issue Nanomaterials for Tissue Engineering Applications)

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14 pages, 8981 KiB

Open AccessArticle

Nanoliposomes from Agro-Resources as Promising Delivery Systems for Chondrocytes

by Arnaud Bianchi, Émilie Velot, Hervé Kempf, Kamil Elkhoury, Laura Sanchez-Gonzalez, Michel Linder, Cyril Kahn and Elmira Arab-Tehrany

Int. J. Mol. Sci. 2020, 21(10), 3436; https://doi.org/10.3390/ijms21103436 - 13 May 2020

Cited by 11 | Viewed by 2837

Abstract

Investigations in cartilage biology have been hampered by the limited capacity of chondrocytes, especially in rats and humans, to be efficiently transfected. Liposomes are a promising delivery system due to their lipid bilayer structure similar to a biological membrane. Here we used natural rapeseed lecithin, which contains a high level of mono- and poly-unsaturated fatty acids, to evaluate the cytocompatibility of these phospholipids as future potential carriers of biomolecules in joint regenerative medicine. Results show that appropriate concentrations of nanoliposome rapeseed lecithin under 500 µg/mL were safe for chondrocytes and did not induce any alterations of their phenotype. Altogether, these results sustain that they could represent a novel natural carrier to deliver active substances into cartilage cells. Full article

(This article belongs to the Special Issue Nanomaterials for Tissue Engineering Applications)

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Review

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27 pages, 2157 KiB

Open AccessReview

Advancement of Nanobiomaterials to Deliver Natural Compounds for Tissue Engineering Applications

by Sathish Sundar Dhilip Kumar and Heidi Abrahamse

Int. J. Mol. Sci. 2020, 21(18), 6752; https://doi.org/10.3390/ijms21186752 - 15 Sep 2020

Cited by 13 | Viewed by 3432

Abstract

Recent advancement in nanotechnology has provided a wide range of benefits in the biological sciences, especially in the field of tissue engineering and wound healing. Nanotechnology provides an easy process for designing nanocarrier-based biomaterials for the purpose and specific needs of tissue engineering applications. Naturally available medicinal compounds have unique clinical benefits, which can be incorporated into nanobiomaterials and enhance their applications in tissue engineering. The choice of using natural compounds in tissue engineering improves treatment modalities and can deal with side effects associated with synthetic drugs. In this review article, we focus on advances in the use of nanobiomaterials to deliver naturally available medicinal compounds for tissue engineering application, including the types of biomaterials, the potential role of nanocarriers, and the various effects of naturally available medicinal compounds incorporated scaffolds in tissue engineering. Full article

(This article belongs to the Special Issue Nanomaterials for Tissue Engineering Applications)

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29 pages, 4050 KiB

Open AccessReview

Nanostructured Materials for Artificial Tissue Replacements

by Jana Pryjmaková, Markéta Kaimlová, Tomáš Hubáček, Václav Švorčík and Jakub Siegel

Int. J. Mol. Sci. 2020, 21(7), 2521; https://doi.org/10.3390/ijms21072521 - 05 Apr 2020

Cited by 27 | Viewed by 3931

Abstract

This paper review current trends in applications of nanomaterials in tissue engineering. Nanomaterials applicable in this area can be divided into two groups: organic and inorganic. Organic nanomaterials are especially used for the preparation of highly porous scaffolds for cell cultivation and are represented by polymeric nanofibers. Inorganic nanomaterials are implemented as they stand or dispersed in matrices promoting their functional properties while preserving high level of biocompatibility. They are used in various forms (e.g., nano- particles, -tubes and -fibers)—and when forming the composites with organic matrices—are able to enhance many resulting properties (biologic, mechanical, electrical and/or antibacterial). For this reason, this contribution points especially to such type of composite nanomaterials. Basic information on classification, properties and application potential of single nanostructures, as well as complex scaffolds suitable for 3D tissues reconstruction is provided. Examples of practical usage of these structures are demonstrated on cartilage, bone, neural, cardiac and skin tissue regeneration and replacements. Nanomaterials open up new ways of treatments in almost all areas of current tissue regeneration, especially in tissue support or cell proliferation and growth. They significantly promote tissue rebuilding by direct replacement of damaged tissues. Full article

(This article belongs to the Special Issue Nanomaterials for Tissue Engineering Applications)

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