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Special Issue "Biomaterials for Soft and Hard Tissue Regeneration"

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 (30 September 2019).

Special Issue Editors

Dr. Mike Barbeck
E-Mail Website
Guest Editor
Department of Oral and Maxillofacial Surgery, University Hospital Hamburg- Eppendorf, D-20246 Hamburg, Germany
Interests: bone substitutes; collagen-based biomaterials for soft and hard tissue regeneration; foreign body response to biomaterials; inflammation; degradation processes of biomaterials; phagocytosis; vascularization; histology; immunohistochemistry; histomorphometry
Dr. Ole Jung
E-Mail Website
Guest Editor
Department of Oral Maxillofacial Surgery, Division of Regenerative Orofacial Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany
Interests: magnesium, magnesium corrosion, magnesium degradation, surfaces for biomaterials, surface kinetics, surface interactios, bone regeneration, in vitro standardization
Prof. Dr. Reiner Schnettler
E-Mail Website
Guest Editor
Department of Oral Maxillofacial Surgery, Division of Regenerative Orofacial Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany
Interests: tissue engineering; cell–material interactions; cell–cell interactions; cell interactions/crosstalk; drug delivery bone substitutes; ossoinduction; osseoconduction; osteogenesis
Prof. Dr. Volker Alt
E-Mail Website
Guest Editor
Department of Trauma Surgery, Justus-Liebig-University Giessen, Rudolf-Buchheim-Str. 7, 35385 Giessen, Germany
Interests: tissue engineering, bone tissue repair, in vivo, bone substitutes, metals for in vivo application, foreign body response

Special Issue Information

Dear Colleagues,

The regeneration of hard and soft tissues aided by biomaterials is of great clinical relevance. A variety of biomaterials for both soft and hard tissue indications are already available as well as a large number of adaptations that are continually being developed. Moreover, radically new and smart materials as well as manufacturing methods are in the focus of biomaterial research. Altogether, these biomaterials are engineered to be bioactive or bioresorbable, whilst also promoting tissue regeneration to the state of a restitutio ad integrum. For both the analysis of scientific issues that are still unsolved and for the evaluation of the biocompatibility of biomaterials, preclinical in vitro and in vivo studies, as well as clinical investigations are mandatory.

The regeneration of hard and soft tissues aided by biomaterials is of great clinical relevance. A variety of biomaterials for both soft and hard tissue indications are already available as well as a large number of adaptations that are continually being developed. Moreover, radically new and smart materials as well as manufacturing methods are in the focus of biomaterial research. Altogether, these biomaterials are engineered to be bioactive or bioresorbable, whilst also promoting tissue regeneration to the state of a restitutio ad integrum. For both the analysis of scientific issues that are still unsolved and for the evaluation of the biocompatibility of biomaterials, preclinical in vitro and in vivo studies, as well as clinical investigations are mandatory.

In this special issue, we would like to present new insights into the underlying cellular and molecular interactions of biomaterials for hard and soft tissue regeneration. Particularly, this special issue seeks for studies describing radically new and smart materials, innovative material processing techniques as well as interactions of materials of both classes with the immune system and relations of immune responses to biomaterials with healing processes. Thus, contributions (reviews and/or original papers) on new biomaterials for hard and soft tissue regeneration and cellular or molecular interactions with biomaterials are welcome.

Dr. Mike Barbeck
Dr. Ole Jung
Prof. Dr. Reiner Schnettler
Prof. Dr. Volker Alt
Guest Editors

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • hard and soft tissue regeneration
  • smart biomaterials
  • innovative material processing techniques
  • immune responses to biomaterials
  • molecular interactions with smart biomaterials

Published Papers (8 papers)

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Research

Open AccessArticle
Cytocompatibility of Titanium, Zirconia and Modified PEEK after Surface Treatment Using UV Light or Non-Thermal Plasma
Int. J. Mol. Sci. 2019, 20(22), 5596; https://doi.org/10.3390/ijms20225596 - 08 Nov 2019
Abstract
A number of modifications have been developed in order to enhance surface cytocompatibility for prosthetic support of dental implants. Among them, ultraviolet (UV) light and non-thermal plasma (NTP) treatment are promising methods. The objective of this study was to compare the effects of [...] Read more.
A number of modifications have been developed in order to enhance surface cytocompatibility for prosthetic support of dental implants. Among them, ultraviolet (UV) light and non-thermal plasma (NTP) treatment are promising methods. The objective of this study was to compare the effects of UV light and NTP on machined titanium, zirconia and modified polyetheretherketone (PEEK, BioHPP) surfaces in vitro. Machined samples of titanium, zirconia and BioHPP were treated by UV light and NTP of argon or oxygen for 12 min each. Non-treated disks were set as controls. A mouse fibroblast and a human gingival fibroblast cell line were used for in vitro experiments. After 2, 24 and 48 h of incubation, the attachment, viability and cytotoxicity of cells on surfaces were assessed. Results: Titanium, zirconia and BioHPP surfaces treated by UV light and oxygen plasma were more favorable to the early attachment of soft-tissue cells than non-treated surfaces, and the number of cells on those treated surfaces was significantly increased after 2, 24 and 48 h of incubation (p < 0.05). However, the effects of argon plasma treatment on the cytocompatibility of soft tissue cells varied with the type of cells and the treated material. UV light and oxygen plasma treatments may improve the attachment of fibroblast cells on machined titanium, zirconia and PEEK surfaces, that are materials for prosthetic support of dental implants. Full article
(This article belongs to the Special Issue Biomaterials for Soft and Hard Tissue Regeneration)
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Open AccessArticle
Graphene Oxide Enhances Chitosan-Based 3D Scaffold Properties for Bone Tissue Engineering
Int. J. Mol. Sci. 2019, 20(20), 5077; https://doi.org/10.3390/ijms20205077 - 13 Oct 2019
Abstract
The main goal of bone tissue engineering (BTE) is to refine and repair major bone defects based on bioactive biomaterials with distinct properties that can induce and support bone tissue formation. Graphene and its derivatives, such as graphene oxide (GO), display optimal properties [...] Read more.
The main goal of bone tissue engineering (BTE) is to refine and repair major bone defects based on bioactive biomaterials with distinct properties that can induce and support bone tissue formation. Graphene and its derivatives, such as graphene oxide (GO), display optimal properties for BTE, being able to support cell growth and proliferation, cell attachment, and cytoskeleton development as well as the activation of osteogenesis and bone development pathways. Conversely, the presence of GO within a polymer matrix produces favorable changes to scaffold morphologies that facilitate cell attachment and migration i.e., more ordered morphologies, greater surface area, and higher total porosity. Therefore, there is a need to explore the potential of GO for tissue engineering applications and regenerative medicine. Here, we aim to promote one novel scaffold based on a natural compound of chitosan, improved with 3 wt.% GO, for BTE approaches, considering its good biocompatibility, remarkable 3D characteristics, and ability to support stem cell differentiation processes towards the bone lineage. Full article
(This article belongs to the Special Issue Biomaterials for Soft and Hard Tissue Regeneration)
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Open AccessArticle
In Vivo Simulation of Magnesium Degradability Using a New Fluid Dynamic Bench Testing Approach
Int. J. Mol. Sci. 2019, 20(19), 4859; https://doi.org/10.3390/ijms20194859 - 30 Sep 2019
Abstract
The degradation rate of magnesium (Mg) alloys is a key parameter to develop Mg-based biomaterials and ensure in vivo-mechanical stability as well as to minimize hydrogen gas production, which otherwise can lead to adverse effects in clinical applications. However, in vitro and in [...] Read more.
The degradation rate of magnesium (Mg) alloys is a key parameter to develop Mg-based biomaterials and ensure in vivo-mechanical stability as well as to minimize hydrogen gas production, which otherwise can lead to adverse effects in clinical applications. However, in vitro and in vivo results of the same material often differ largely. In the present study, a dynamic test bench with several single bioreactor cells was constructed to measure the volume of hydrogen gas which evolves during magnesium degradation to indicate the degradation rate in vivo. Degradation medium comparable with human blood plasma was used to simulate body fluids. The media was pumped through the different bioreactor cells under a constant flow rate and 37 °C to simulate physiological conditions. A total of three different Mg groups were successively tested: Mg WE43, and two different WE43 plasma electrolytically oxidized (PEO) variants. The results were compared with other methods to detect magnesium degradation (pH, potentiodynamic polarization (PDP), cytocompatibility, SEM (scanning electron microscopy)). The non-ceramized specimens showed the highest degradation rates and vast standard deviations. In contrast, the two PEO samples demonstrated reduced degradation rates with diminished standard deviation. The pH values showed above-average constant levels between 7.4–7.7, likely due to the constant exchange of the fluids. SEM revealed severe cracks on the surface of WE43 after degradation, whereas the ceramized surfaces showed significantly decreased signs of corrosion. PDP results confirmed the improved corrosion resistance of both PEO samples. While WE43 showed slight toxicity in vitro, satisfactory cytocompatibility was achieved for the PEO test samples. In summary, the dynamic test bench constructed in this study enables reliable and simple measurement of Mg degradation to simulate the in vivo environment. Furthermore, PEO treatment of magnesium is a promising method to adjust magnesium degradation. Full article
(This article belongs to the Special Issue Biomaterials for Soft and Hard Tissue Regeneration)
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Open AccessArticle
A New Approach for the Fabrication of Cytocompatible PLLA-Magnetite Nanoparticle Composite Scaffolds
Int. J. Mol. Sci. 2019, 20(19), 4664; https://doi.org/10.3390/ijms20194664 - 20 Sep 2019
Abstract
Magnetic biomimetic scaffolds of poly(L-lactide) (PLLA) and nanoparticles of magnetite (nFe3O4) are prepared in a wide ratio of compositions by lyophilization for bone regeneration. The magnetic properties, cytotoxicity, and the in vitro degradation of these porous materials are closely [...] Read more.
Magnetic biomimetic scaffolds of poly(L-lactide) (PLLA) and nanoparticles of magnetite (nFe3O4) are prepared in a wide ratio of compositions by lyophilization for bone regeneration. The magnetic properties, cytotoxicity, and the in vitro degradation of these porous materials are closely studied. The addition of magnetite at 50 °C was found to produce an interaction reaction between the ester groups of the PLLA and the metallic cations of the magnetite, causing the formation of complexes. This fact was confirmed by the analysis of the infrared spectroscopy and the gel permeation chromatography test results. They, respectively, showed a displacement of the absorption bands of the carbonyl group (C=O) of the PLLA and a scission of the polymer chains. The iron from the magnetite acted as a catalyser of the macromolecular scission reaction, which determines the final biomedical applications of the scaffolds—it does so because the reaction shortens the degradation process without appearing to influence its toxicity. None of the samples studied in the tests presented cytotoxicity, even at 70% magnetite concentrations. Full article
(This article belongs to the Special Issue Biomaterials for Soft and Hard Tissue Regeneration)
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Open AccessArticle
Preparation of Gelatin and Gelatin/Hyaluronic Acid Cryogel Scaffolds for the 3D Culture of Mesothelial Cells and Mesothelium Tissue Regeneration
Int. J. Mol. Sci. 2019, 20(18), 4527; https://doi.org/10.3390/ijms20184527 - 12 Sep 2019
Abstract
Mesothelial cells are specific epithelial cells that are lined in the serosal cavity and internal organs. Nonetheless, few studies have explored the possibility to culture mesothelial cells in a three-dimensional (3D) scaffold for tissue engineering applications. Towards this end, we fabricated macroporous scaffolds [...] Read more.
Mesothelial cells are specific epithelial cells that are lined in the serosal cavity and internal organs. Nonetheless, few studies have explored the possibility to culture mesothelial cells in a three-dimensional (3D) scaffold for tissue engineering applications. Towards this end, we fabricated macroporous scaffolds from gelatin and gelatin/hyaluronic acid (HA) by cryogelation, and elucidated the influence of HA on cryogel properties and the cellular phenotype of mesothelial cells cultured within the 3D scaffolds. The incorporation of HA was found not to significantly change the pore size, porosity, water uptake kinetics, and swelling ratios of the cryogel scaffolds, but led to a faster scaffold degradation in the collagenase solution. Adding 5% HA in the composite cryogels also decreased the ultimate compressive stress (strain) and toughness of the scaffold, but enhanced the elastic modulus. From the in vitro cell culture, rat mesothelial cells showed quantitative cell viability in gelatin (G) and gelatin/HA (GH) cryogels. Nonetheless, mesothelial cells cultured in GH cryogels showed a change in the cell morphology and cytoskeleton arrangement, reduced cell proliferation rate, and downregulation of the mesothelium specific maker gene expression. The production of key mesothelium proteins E-cadherin and calretinin were also reduced in the GH cryogels. Choosing the best G cryogels for in vivo studies, the cell/cryogel construct was used for the transplantation of allograft mesothelial cells for mesothelium reconstruction in rats. A mesothelium layer similar to the native mesothelium tissue could be obtained 21 days post-implantation, based on hematoxylin and eosin (H&E) and immunohistochemical staining. Full article
(This article belongs to the Special Issue Biomaterials for Soft and Hard Tissue Regeneration)
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Open AccessArticle
Versatile Biomaterial Platform Enriched with Graphene Oxide and Carbon Nanotubes for Multiple Tissue Engineering Applications
Int. J. Mol. Sci. 2019, 20(16), 3868; https://doi.org/10.3390/ijms20163868 - 08 Aug 2019
Cited by 3
Abstract
Carbon-based nanomaterials, such as graphene oxide (GO) or carbon nanotubes (CNTs) are currently used in various medical applications due to their positive influence on biocompatibility, adhesion, proliferation, and differentiation, as well as their contribution to modulating cell behavior in response to nanomaterial substrates. [...] Read more.
Carbon-based nanomaterials, such as graphene oxide (GO) or carbon nanotubes (CNTs) are currently used in various medical applications due to their positive influence on biocompatibility, adhesion, proliferation, and differentiation, as well as their contribution to modulating cell behavior in response to nanomaterial substrates. In this context, in this study, novel flexible membranes based on cellulose acetate (CA) enriched with CNT and GO in different percentages were tested for their versatility to be used as substrates for soft or hard tissue engineering (TE), namely, for their ability to support human adipose-derived stem cells (hASCs) adhesion during adipogenic or osteogenic differentiation. For this purpose, differentiation markers were assessed both at gene and protein levels, while histological staining was performed to show the evolution of the processes in response to CA-CNT-GO substrates. Micro-CT analysis indicated porous morphologies with open and interconnected voids. A slightly lower total porosity was obtained for the samples filled with the highest amount of GO and CNTs, but thicker walls, larger and more uniform pores were obtained, providing beneficial effects on cell behavior and increased mechanical stability. The addition of 1 wt% GO and CNT to the biocomposites enhanced hASCs adhesion and cytoskeleton formation. The evolution of both adipogenic and osteogenic differentiation processes was found to be augmented proportionally to the GO-CNT concentration. In conclusion, CA-CNT-GO biomaterials displayed good properties and versatility as platforms for cell differentiation with potential as future implantable materials in TE applications. Full article
(This article belongs to the Special Issue Biomaterials for Soft and Hard Tissue Regeneration)
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Open AccessArticle
The Addition of High Doses of Hyaluronic Acid to a Biphasic Bone Substitute Decreases the Proinflammatory Tissue Response
Int. J. Mol. Sci. 2019, 20(8), 1969; https://doi.org/10.3390/ijms20081969 - 22 Apr 2019
Cited by 1
Abstract
Biphasic bone substitutes (BBS) are currently well-established biomaterials. Through their constant development, even natural components like hyaluronic acid (HY) have been added to improve both their handling and also their regenerative properties. However, little knowledge exists regarding the consequences of the addition of [...] Read more.
Biphasic bone substitutes (BBS) are currently well-established biomaterials. Through their constant development, even natural components like hyaluronic acid (HY) have been added to improve both their handling and also their regenerative properties. However, little knowledge exists regarding the consequences of the addition of HY to their biocompatibility and the inflammatory tissue reactions. Thus, the present study was conducted, aiming to analyze the influence of two different amounts of high molecular weight HY (HMWHY), combined with a BBS, on in vitro biocompatibility and in vivo tissue reaction. Established in vitro procedures, using L929 cells, were used for cytocompatibility analyses under the test conditions of DIN EN:ISO 10993-5. For the in vivo part of the study, calvarial defects were created in 20 Wistar rats and subsequently filled with BBS, and BBS combined with two different HMWHY amounts, i.e., BBS + HY(L) and BBS + HY(H). As controls, empty defects were used. Established histological, immunohistochemical, and histomorphometrical methods were applied to analyze the tissue reactions to the three different materials, including the induction of pro- and anti-inflammatory macrophages and multinucleated giant cells (BMGCs). The in vitro results showed that none of the materials or compositions caused biological damage to the L929 cells and can be considered to be non-toxic. The in vivo results showed that only the addition of high doses of HY to a biphasic bone substitute significantly decreases the occurrence of pro-inflammatory macrophages (* p < 0.05), comparable to the numbers found in the control group, while no significant differences within the three study groups for M2-macrophages nor BMGCs were detected. In conclusion, the addition of different amounts of HMWHY does not seem to affect the inflammation response to BBS, while improving the material handling properties. Full article
(This article belongs to the Special Issue Biomaterials for Soft and Hard Tissue Regeneration)
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Open AccessArticle
3D-Printed Bioactive Calcium Silicate/Poly-ε-Caprolactone Bioscaffolds Modified with Biomimetic Extracellular Matrices for Bone Regeneration
Int. J. Mol. Sci. 2019, 20(4), 942; https://doi.org/10.3390/ijms20040942 - 21 Feb 2019
Cited by 10
Abstract
Currently, clinically available orthopedic implants are extremely biocompatible but they lack specific biological characteristics that allow for further interaction with surrounding tissues. The extracellular matrix (ECM)-coated scaffolds have received considerable interest for bone regeneration due to their ability in upregulating regenerative cellular behaviors. [...] Read more.
Currently, clinically available orthopedic implants are extremely biocompatible but they lack specific biological characteristics that allow for further interaction with surrounding tissues. The extracellular matrix (ECM)-coated scaffolds have received considerable interest for bone regeneration due to their ability in upregulating regenerative cellular behaviors. This study delves into the designing and fabrication of three-dimensional (3D)-printed scaffolds that were made out of calcium silicate (CS), polycaprolactone (PCL), and decellularized ECM (dECM) from MG63 cells, generating a promising bone tissue engineering strategy that revolves around the concept of enhancing osteogenesis by creating an osteoinductive microenvironment with osteogenesis-promoting dECM. We cultured MG63 on scaffolds to obtain a dECM-coated CS/PCL scaffold and further studied the biological performance of the dECM hybrid scaffolds. The results indicated that the dECM-coated CS/PCL scaffolds exhibited excellent biocompatibility and effectively enhanced cellular adhesion, proliferation, and differentiation of human Wharton’s Jelly mesenchymal stem cells by increasing the expression of osteogenic-related genes. They also presented anti-inflammatory characteristics by showing a decrease in the expression of tumor necrosis factor-alpha (TNF-α) and interleukin-1 (IL-1). Histological analysis of in vivo experiments presented excellent bone regenerative capabilities of the dECM-coated scaffold. Overall, our work presented a promising technique for producing bioscaffolds that can augment bone tissue regeneration in numerous aspects. Full article
(This article belongs to the Special Issue Biomaterials for Soft and Hard Tissue Regeneration)
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