Nanotechnology and Additive Manufacturing for Hard Tissue Regeneration

A special issue of Nanomaterials (ISSN 2079-4991). This special issue belongs to the section "Synthesis, Interfaces and Nanostructures".

Deadline for manuscript submissions: closed (30 November 2021) | Viewed by 21841

Special Issue Editor


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Guest Editor
Department of Biomedical Sciences, College of Life and Health Sciences, Chubu University, 1200 Matsumoto cho, Kasugai, Aichi 487-8501, Japan
Interests: surface modification; chemical and heat treatment; Ti and its alloys; orthopedics and dental implants; bone bonding; antibacterial activity; apatite formation; drug release; porous body; selective laser melting

Special Issue Information

Dear Colleagues,

The role of nanotechnology and additive manufacturing in hard-tissue regeneration has significantly increased. Bone formation, bone bonding, cell viability, cell differentiation, mineralization, inflammation, and other key processes in hard-tissue regeneration are highly dependent on nano-structured surfaces and/or scaffolds. In addition, nanotopology and surface chemistry affect antibacterial activity. A new generation of smart biomaterials improving hard-tissue regeneration while preventing infection is highly desired.

For this Special Issue, we are especially interested in surface modifications of metals, ceramics, and polymers, synthesis of scaffolds, characterization of hard-tissue regeneration processes, and possible applications based on nanotechnology. Manuscripts reporting nanotechnologies applicable to custom-made biomaterials with tailored outer and/or inner structures are also welcome.

Dr. Seiji Yamaguchi
Guest Editor

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Keywords

  • Bone formation
  • Bone bonding
  • Mineralization
  • Cell culture
  • Surface modification
  • Additive manufacturing
  • Drug delivery
  • Antibacterial activity
  • Scaffold

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Published Papers (5 papers)

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Research

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20 pages, 4805 KiB  
Article
Iodine-Loaded Calcium Titanate for Bone Repair with Sustainable Antibacterial Activity Prepared by Solution and Heat Treatment
by Seiji Yamaguchi, Phuc Thi Minh Le, Seine A. Shintani, Hiroaki Takadama, Morihiro Ito, Sara Ferraris and Silvia Spriano
Nanomaterials 2021, 11(9), 2199; https://doi.org/10.3390/nano11092199 - 26 Aug 2021
Cited by 12 | Viewed by 2863
Abstract
In the orthopedic and dental fields, simultaneously conferring titanium (Ti) and its alloy implants with antibacterial and bone-bonding capabilities is an outstanding challenge. In the present study, we developed a novel combined solution and heat treatment that controllably incorporates 0.7% to 10.5% of [...] Read more.
In the orthopedic and dental fields, simultaneously conferring titanium (Ti) and its alloy implants with antibacterial and bone-bonding capabilities is an outstanding challenge. In the present study, we developed a novel combined solution and heat treatment that controllably incorporates 0.7% to 10.5% of iodine into Ti and its alloys by ion exchange with calcium ions in a bioactive calcium titanate. The treated metals formed iodine-containing calcium-deficient calcium titanate with abundant Ti-OH groups on their surfaces. High-resolution XPS analysis revealed that the incorporated iodine ions were mainly positively charged. The surface treatment also induced a shift in the isoelectric point toward a higher pH, which indicated a prevalence of basic surface functionalities. The Ti loaded with 8.6% iodine slowly released 5.6 ppm of iodine over 90 days and exhibited strong antibacterial activity (reduction rate >99%) against methicillin-resistant Staphylococcus aureus (MRSA), S. aureus, Escherichia coli, and S. epidermidis. A long-term stability test of the antibacterial activity on MRSA showed that the treated Ti maintained a >99% reduction until 3 months, and then it gradually decreased after 6 months (to a 97.3% reduction). There was no cytotoxicity in MC3T3-E1 or L929 cells, whereas apatite formed on the treated metal in a simulated body fluid within 3 days. It is expected that the iodine-carrying Ti and its alloys will be particularly useful for orthopedic and dental implants since they reliably bond to bone and prevent infection owing to their apatite formation, cytocompatibility, and sustainable antibacterial activity. Full article
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13 pages, 9733 KiB  
Article
Contact Guidance Effect and Prevention of Microfouling on a Beta Titanium Alloy Surface Structured by Electron-Beam Technology
by Sara Ferraris, Fernando Warchomicka, Jacopo Barberi, Andrea Cochis, Alessandro Calogero Scalia and Silvia Spriano
Nanomaterials 2021, 11(6), 1474; https://doi.org/10.3390/nano11061474 - 2 Jun 2021
Cited by 14 | Viewed by 3101
Abstract
Nano- and micro-structuring of implantable materials constitute a promising approach to introduce mechanical contact guidance effect, drive cells colonization, as well as to prevent bacteria adhesion and biofilm aggregation, through antifouling topography. Accordingly, this paper aims to extend the application of e-beam surface [...] Read more.
Nano- and micro-structuring of implantable materials constitute a promising approach to introduce mechanical contact guidance effect, drive cells colonization, as well as to prevent bacteria adhesion and biofilm aggregation, through antifouling topography. Accordingly, this paper aims to extend the application of e-beam surface texturing and nano-structuring to the beta titanium alloys, which are of great interest for biomedical implants because of the low Young modulus and the reduction of the stress shielding effect. The paper shows that surface texturing on the micro-scale (micro-grooves) is functional to a contact guidance effect on gingival fibroblasts. Moreover, nano-structuring, derived from the e-beam surface treatment, is effective to prevent microfouling. In fact, human fibroblasts were cultivated directly onto grooved specimens showing to sense the surface micro-structure thus spreading following the grooves’ orientation. Moreover, Staphylococcus aureus colonies adhesion was prevented by the nano-topographies in comparison to the mirror-polished control, thus demonstrating promising antifouling properties. Furthermore, the research goes into detail to understand the mechanism of microfouling prevention due to nano-topography and microstructure. Full article
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17 pages, 3817 KiB  
Article
Extracellular Vesicle-Based Coatings Enhance Bioactivity of Titanium Implants—SurfEV
by Taisa Nogueira Pansani, Thanh Huyen Phan, Qingyu Lei, Alexey Kondyurin, Bill Kalionis and Wojciech Chrzanowski
Nanomaterials 2021, 11(6), 1445; https://doi.org/10.3390/nano11061445 - 29 May 2021
Cited by 11 | Viewed by 4404
Abstract
Extracellular vesicles (EVs) are nanoparticles released by cells that contain a multitude of biomolecules, which act synergistically to signal multiple cell types. EVs are ideal candidates for promoting tissue growth and regeneration. The tissue regenerative potential of EVs raises the tantalizing possibility that [...] Read more.
Extracellular vesicles (EVs) are nanoparticles released by cells that contain a multitude of biomolecules, which act synergistically to signal multiple cell types. EVs are ideal candidates for promoting tissue growth and regeneration. The tissue regenerative potential of EVs raises the tantalizing possibility that immobilizing EVs on implant surfaces could potentially generate highly bioactive and cell-instructive surfaces that would enhance implant integration into the body. Such surfaces could address a critical limitation of current implants, which do not promote bone tissue formation or bond bone. Here, we developed bioactive titanium surface coatings (SurfEV) using two types of EVs: secreted by decidual mesenchymal stem cells (DEVs) and isolated from fermented papaya fluid (PEVs). For each EV type, we determined the size, morphology, and molecular composition. High concentrations of DEVs enhanced cell proliferation, wound closure, and migration distance of osteoblasts. In contrast, the cell proliferation and wound closure decreased with increasing concentration of PEVs. DEVs enhanced Ca/P deposition on the titanium surface, which suggests improvement in bone bonding ability of the implant (i.e., osteointegration). EVs also increased production of Ca and P by osteoblasts and promoted the deposition of mineral phase, which suggests EVs play key roles in cell mineralization. We also found that DEVs stimulated the secretion of secondary EVs observed by the presence of protruding structures on the cell membrane. We concluded that, by functionalizing implant surfaces with specialized EVs, we will be able to enhance implant osteointegration by improving hydroxyapatite formation directly at the surface and potentially circumvent aseptic loosening of implants. Full article
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16 pages, 4767 KiB  
Article
Bioactivation Treatment with Mixed Acid and Heat on Titanium Implants Fabricated by Selective Laser Melting Enhances Preosteoblast Cell Differentiation
by Phuc Thi Minh Le, Seine A. Shintani, Hiroaki Takadama, Morihiro Ito, Tatsuya Kakutani, Hisashi Kitagaki, Shuntaro Terauchi, Takaaki Ueno, Hiroyuki Nakano, Yoichiro Nakajima, Kazuya Inoue, Tomiharu Matsushita and Seiji Yamaguchi
Nanomaterials 2021, 11(4), 987; https://doi.org/10.3390/nano11040987 - 12 Apr 2021
Cited by 10 | Viewed by 2580
Abstract
Selective laser melting (SLM) is a promising technology capable of producing individual characteristics with a high degree of surface roughness for implants. These surfaces can be modified so as to increase their osseointegration, bone generation and biocompatibility, features which are critical to their [...] Read more.
Selective laser melting (SLM) is a promising technology capable of producing individual characteristics with a high degree of surface roughness for implants. These surfaces can be modified so as to increase their osseointegration, bone generation and biocompatibility, features which are critical to their clinical success. In this study, we evaluated the effects on preosteoblast proliferation and differentiation of titanium metal (Ti) with a high degree of roughness (Ra = 5.4266 ± 1.282 µm) prepared by SLM (SLM-Ti) that was also subjected to surface bioactive treatment by mixed acid and heat (MAH). The results showed that the MAH treatment further increased the surface roughness, wettability and apatite formation capacity of SLM-Ti, features which are useful for cell attachment and bone bonding. Quantitative measurement of osteogenic-related gene expression by RT-PCR indicated that the MC3T3-E1 cells on the SLM-Ti MAH surface presented a stronger tendency towards osteogenic differentiation at the genetic level through significantly increased expression of Alp, Ocn, Runx2 and Opn. We conclude that bio-activated SLM-Ti enhanced preosteoblast differentiation. These findings suggest that the mixed acid and heat treatment on SLM-Ti is promising method for preparing the next generation of orthopedic and dental implants because of its apatite formation and cell differentiation capability. Full article
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Review

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40 pages, 4501 KiB  
Review
Electrospun Nanofibers for Improved Angiogenesis: Promises for Tissue Engineering Applications
by Simin Nazarnezhad, Francesco Baino, Hae-Won Kim, Thomas J. Webster and Saeid Kargozar
Nanomaterials 2020, 10(8), 1609; https://doi.org/10.3390/nano10081609 - 17 Aug 2020
Cited by 78 | Viewed by 7867
Abstract
Angiogenesis (or the development of new blood vessels) is a key event in tissue engineering and regenerative medicine; thus, a number of biomaterials have been developed and combined with stem cells and/or bioactive molecules to produce three-dimensional (3D) pro-angiogenic constructs. Among the various [...] Read more.
Angiogenesis (or the development of new blood vessels) is a key event in tissue engineering and regenerative medicine; thus, a number of biomaterials have been developed and combined with stem cells and/or bioactive molecules to produce three-dimensional (3D) pro-angiogenic constructs. Among the various biomaterials, electrospun nanofibrous scaffolds offer great opportunities for pro-angiogenic approaches in tissue repair and regeneration. Nanofibers made of natural and synthetic polymers are often used to incorporate bioactive components (e.g., bioactive glasses (BGs)) and load biomolecules (e.g., vascular endothelial growth factor (VEGF)) that exert pro-angiogenic activity. Furthermore, seeding of specific types of stem cells (e.g., endothelial progenitor cells) onto nanofibrous scaffolds is considered as a valuable alternative for inducing angiogenesis. The effectiveness of these strategies has been extensively examined both in vitro and in vivo and the outcomes have shown promise in the reconstruction of hard and soft tissues (mainly bone and skin, respectively). However, the translational of electrospun scaffolds with pro-angiogenic molecules or cells is only at its beginning, requiring more research to prove their usefulness in the repair and regeneration of other highly-vascularized vital tissues and organs. This review will cover the latest progress in designing and developing pro-angiogenic electrospun nanofibers and evaluate their usefulness in a tissue engineering and regenerative medicine setting. Full article
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