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Biomaterials for Bone Tissue Engineering 2.0

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 (15 March 2022) | Viewed by 42372

Special Issue Editors


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Guest Editor
1. BerlinAnalytix GmbH, Ullsteinstrasse 109, 12109 Berlin, Germany
2. Department of Ceramic Materials, Chair of Advanced Ceramic Materials, Institute for Materials Science and Technologies, Technical University Berlin, Berlin, Germany
Interests: dental barrier membranes; collagen; cross-linking; magnesium membranes; degradation; bone tissue regeneration
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Guest Editor
1. Department of Biology and Human Genetics, Faculty of Medicine, University of Niš, 18000 Niš, Serbia
2. Department for Cell and Tissue Engineering, Scientific Research Center for Biomedicine, Faculty of Medicine, University of Niš, 18000 Niš, Serbia
Interests: skeletal tissues regeneration assisted by biomaterials and stem cells; biomaterials; tissue engineering models; regenerative medicine; examination of biological activity and toxicity of the various substances in animal models in vivo and cell models in vitro; macrophages; stem cells; cell and molecular biology; human genetics
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The worldwide clinical demand for bone regeneration is a problematic issue in orthopaedic and maxillofacial surgery. The application of autologous bone is still the standard in bone transplantation. Due to the limited quantity of bone available for harvest and the poor quality of bone transplants, especially in elderly patients due to bone diseases such as osteoporosis, surgeons are looking for alternatives such as bone substitute materials. The ideal grafting material enables the regeneration of bony defects up to the condition of a restitutio ad integrum and should combine the basic mechanism of fracture healing, namely osteogenesis, osteoinduction and osteoconduction. In the last few decades, a variety of bone substitute materials with different physicochemical properties have been developed and analyzed to optimize the process of bone regeneration. Furthermore, various different growth factors, cytokines and antibiotics have been incorporated into bone substitutes and matrices as so-called “composite bone grafts” in order to enhance bone healing. Moreover, different tissue engineering strategies, such as combinations with extracellular matrix proteins and/or different cell types (e.g., osteoblasts, mesenchymal stem cells or endothelial cells) have been developed with the aim of improving the regenerative properties of bone substitute materials. However, no alternative to autologous bone has been found; thus there is a need for ongoing research to develop a composite bone graft that combines osteogenesis with inductive and conductive properties. In this context, preclinical in vitro and in vivo studies, as well as clinical trials analyzing fundamental molecular processes, are crucial to define the regeneration mechanisms of new materials und tissue engineering concepts.

This Special Issue focuses on the various aspects of interactions of bone substitutes with cells and tissues. Thus, we invite to contributions of reviews and/or original papers reporting new results in the field of bone substitute development and bone tissue engineering concepts, including in vitro and in vivo analyses, as well as clinical studies, with a focus on new molecular insights.

Dr. Mike Barbeck
Dr. Ole Jung
Prof. Dr. Stevo Najman
Guest Editors

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Keywords

  • bone tissue regeneration
  • bone substitute
  • bone tissue engineering
  • tissue reactions
  • biomaterial

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Published Papers (13 papers)

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Research

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18 pages, 3449 KiB  
Article
CSBD Healing in Rats after Application of Bovine Xenogeneic Biomaterial Enriched with Magnesium Alloy
by Ana Terezija Jerbić Radetić, Sanja Zoričić Cvek, Matej Tomas, Igor Erjavec, Matko Oguić, Željka Perić Kačarević and Olga Cvijanović Peloza
Int. J. Mol. Sci. 2021, 22(16), 9089; https://doi.org/10.3390/ijms22169089 - 23 Aug 2021
Cited by 7 | Viewed by 2681
Abstract
Xenogeneic biomaterials Cerbone® and OsteoBiol® are widely used in oral implantology. In dental practice, xenogeneic biomaterial is usually combined with autologous bone to provide bone volume stability needed for long-term dental implants. Magnesium alloy implants dissolve and form mineral corrosion layer [...] Read more.
Xenogeneic biomaterials Cerbone® and OsteoBiol® are widely used in oral implantology. In dental practice, xenogeneic biomaterial is usually combined with autologous bone to provide bone volume stability needed for long-term dental implants. Magnesium alloy implants dissolve and form mineral corrosion layer that is directly in contact with bone tissue, allowing deposition of the newly formed bone. CSBD heals by intramembranous ossification and therefore is a convenient model for analyses of ostoconductive and osteoinductive properties of different type of biomaterials. Magnesium alloy-enriched biomaterials have not yet been applied in oral implantology. Therefore, the aim of the current study was to investigate biological properties of potentially new bovine xenogeneic biomaterial enriched with magnesium alloy in a 5 mm CSBD model. Osteoconductive properties of Cerabone®, Cerabone® + Al. bone, and OsteoBiol® were also analyzed. Dynamics of bone healing was followed up on the days 3, 7, 15, 21, and 30. Calvary bone samples were analyzed by micro-CT, and values of the bone morphometric parameters were assessed. Bone samples were further processed for histological and immunohistochemical analyses. Histological observation revealed CSBD closure at day 30 of the given xenogeneic biomaterial groups, with the exception of the control group. TNF-α showed high intensity of expression at the sites of MSC clusters that underwent ossification. Osx was expressed in pre-osteoblasts, which were differentiated into mature osteoblasts and osteocytes. Results of the micro-CT analyses showed linear increase in bone volume of all xenogeneic biomaterial groups and also in the control. The highest average values of bone volume were found for the Cerabone® + Mg group. In addition, less residual biomaterial was estimated in the Cerabone® + Mg group than in the Cerabone® group, indicating its better biodegradation during CSBD healing. Overall, the magnesium alloy xenogeneic biomaterial demonstrated key properties of osteoinduction and biodegradidibility during CSBD healing, which is the reason why it should be recommended for application in clinical practice of oral implantology. Full article
(This article belongs to the Special Issue Biomaterials for Bone Tissue Engineering 2.0)
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16 pages, 5517 KiB  
Article
Investigating the Intermediate Water Feature of Hydrated Titanium Containing Bioactive Glass
by Mostafa Mabrouk, Hanan H. Beherei, Yukiko Tanaka and Masaru Tanaka
Int. J. Mol. Sci. 2021, 22(15), 8038; https://doi.org/10.3390/ijms22158038 - 27 Jul 2021
Cited by 11 | Viewed by 2042
Abstract
Intermediate water (IW) in hydrated bioactive glasses remains uninvestigated. We obtained titanium (Ti)-containing bioactive glasses (BGTs) (Ti at 5%, 7.5% and 10% of the glass system) using the sol–gel technique. Their thermal, physicochemical, and morphological properties, before and after Ti-doping, were analysed using [...] Read more.
Intermediate water (IW) in hydrated bioactive glasses remains uninvestigated. We obtained titanium (Ti)-containing bioactive glasses (BGTs) (Ti at 5%, 7.5% and 10% of the glass system) using the sol–gel technique. Their thermal, physicochemical, and morphological properties, before and after Ti-doping, were analysed using DTA, XRD, FTIR, TEM, and SEM accessorised with EDAX, and size distribution and zeta potential surface charges were determined using a NanoZetasizer. The IW in hydrated BGTs was investigated by cooling and heating runs of DSC measurements. Moreover, the mode of death in an osteosarcoma cell line (MG63) was evaluated at different times of exposure to BGT discs. Ti doping had no remarkable effect on the thermal, physicochemical, and morphological properties of BGTs. However, the morphology, size, and charges of BGT nano-powders were slightly changed after inclusion of Ti compared with those of BGT0; for example, the particle size increased with increasing Ti content (from 4–5 to 7–28 nm). The IW content was enhanced in the presence of Ti. The mode of cell death revealed the effect of IW content on the proliferation of cells exposed to BGTs. These findings should help improve the biocompatibility of inorganic biomaterials. Full article
(This article belongs to the Special Issue Biomaterials for Bone Tissue Engineering 2.0)
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12 pages, 4833 KiB  
Article
Evaluation of MC3T3-E1 Cell Osteogenesis in Different Cell Culture Media
by Makoto Izumiya, Miyu Haniu, Katsuya Ueda, Haruka Ishida, Chuang Ma, Hirokazu Ideta, Atsushi Sobajima, Koki Ueshiba, Takeshi Uemura, Naoto Saito and Hisao Haniu
Int. J. Mol. Sci. 2021, 22(14), 7752; https://doi.org/10.3390/ijms22147752 - 20 Jul 2021
Cited by 24 | Viewed by 7946
Abstract
Many biomaterials have been evaluated using cultured cells. In particular, osteoblast-like cells are often used to evaluate the osteocompatibility, hard-tissue-regeneration, osteoconductive, and osteoinductive characteristics of biomaterials. However, the evaluation of biomaterial osteogenesis-inducing capacity using osteoblast-like cells is not standardized; instead, it is performed [...] Read more.
Many biomaterials have been evaluated using cultured cells. In particular, osteoblast-like cells are often used to evaluate the osteocompatibility, hard-tissue-regeneration, osteoconductive, and osteoinductive characteristics of biomaterials. However, the evaluation of biomaterial osteogenesis-inducing capacity using osteoblast-like cells is not standardized; instead, it is performed under laboratory-specific culture conditions with different culture media. However, the effect of different media conditions on bone formation has not been investigated. Here, we aimed to evaluate the osteogenesis of MC3T3-E1 cells, one of the most commonly used osteoblast-like cell lines for osteogenesis evaluation, and assayed cell proliferation, alkaline phosphatase activity, expression of osteoblast markers, and calcification under varying culture media conditions. Furthermore, the various media conditions were tested in uncoated plates and plates coated with collagen type I and poly-L-lysine, highly biocompatible molecules commonly used as pseudobiomaterials. We found that the type of base medium, the presence or absence of vitamin C, and the freshness of the medium may affect biomaterial regeneration. We posit that an in vitro model that recapitulates in vivo bone formation should be established before evaluating biomaterials. Full article
(This article belongs to the Special Issue Biomaterials for Bone Tissue Engineering 2.0)
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16 pages, 4839 KiB  
Article
Antibacterial Poly(ε-CL)/Hydroxyapatite Electrospun Fibers Reinforced by Poly(ε-CL)-b-poly(ethylene phosphoric acid)
by Ilya Nifant’ev, Dmitry Gavrilov, Alexander Tavtorkin, Maria Chinova, Victoria Besprozvannykh, Pavel Komarov, Vladimir Zaitsev, Irina Podoprigora and Pavel Ivchenko
Int. J. Mol. Sci. 2021, 22(14), 7690; https://doi.org/10.3390/ijms22147690 - 19 Jul 2021
Cited by 6 | Viewed by 2193
Abstract
In bone surgery and orthopedics, bioresorbable materials can be helpful in bone repair and countering post-op infections. Explicit antibacterial activity, osteoinductive and osteoconductive effects are essential to achieving this objective. Nonwoven electrospun (ES) fibers are receiving the close attention of physicians as promising [...] Read more.
In bone surgery and orthopedics, bioresorbable materials can be helpful in bone repair and countering post-op infections. Explicit antibacterial activity, osteoinductive and osteoconductive effects are essential to achieving this objective. Nonwoven electrospun (ES) fibers are receiving the close attention of physicians as promising materials for wound dressing and tissue engineering; potentially, in high contrast with dense materials, ES mats hamper regeneration of the bone extracellular matrix to a lesser extent. The use of the compositions of inherently biodegradable polyesters (poly(ε-caprolactone) PCL, poly(lactoglycolide), etc.), calcium phosphates and antibiotics is highly prospective, but the task of forming ES fibers from such compositions is complicated by the incompatibility of the main organic and inorganic ingredients, polyesters and calcium phosphates. In the present research we report the synthesis of hydroxyapatite (HAp) nanoparticles with uniform morphology, and demonstrate high efficiency of the block copolymer of PCL and poly(ethylene phosphoric acid) (PEPA) as an efficient compatibilizer for PCL/HAp mixtures that are able to form ES fibers with improved mechanical characteristics. The materials obtained in the presence of vancomycin exhibited incremental drug release against Staphylococcus aureus (St. aureus). Full article
(This article belongs to the Special Issue Biomaterials for Bone Tissue Engineering 2.0)
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18 pages, 5359 KiB  
Article
In Vitro and In Vivo Characterization of PLLA-316L Stainless Steel Electromechanical Devices for Bone Tissue Engineering—A Preliminary Study
by Mariana V. Branquinho, Sheila O. Ferreira, Rui D. Alvites, Adriana F. Magueta, Maxim Ivanov, Ana Catarina Sousa, Irina Amorim, Fátima Faria, M. H. V. Fernandes, Paula M. Vilarinho and Ana Colette Maurício
Int. J. Mol. Sci. 2021, 22(14), 7655; https://doi.org/10.3390/ijms22147655 - 17 Jul 2021
Cited by 11 | Viewed by 2729
Abstract
Bone injuries represent a major social and financial impairment, commonly requiring surgical intervention due to a limited healing capacity of the tissue, particularly regarding critical-sized defects and non-union fractures. Regenerative medicine with the application of bone implants has been developing in the past [...] Read more.
Bone injuries represent a major social and financial impairment, commonly requiring surgical intervention due to a limited healing capacity of the tissue, particularly regarding critical-sized defects and non-union fractures. Regenerative medicine with the application of bone implants has been developing in the past decades towards the manufacturing of appropriate devices. This work intended to evaluate medical 316L stainless steel (SS)-based devices covered by a polymer poly (L-lactic acid) (PLLA) coating for bone lesion mechanical and functional support. SS316L devices were subjected to a previously described silanization process, following a three-layer PLLA film coating. Devices were further characterized and evaluated towards their cytocompatibility and osteogenic potential using human dental pulp stem cells, and biocompatibility via subcutaneous implantation in a rat animal model. Results demonstrated PLLA-SS316L devices to present superior in vitro and in vivo outcomes and suggested the PLLA coating to provide osteo-inductive properties to the device. Overall, this work represents a preliminary study on PLLA-SS316L devices’ potential towards bone tissue regenerative techniques, showing promising outcomes for bone lesion support. Full article
(This article belongs to the Special Issue Biomaterials for Bone Tissue Engineering 2.0)
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24 pages, 5984 KiB  
Article
Electrochemical, Tribological and Biocompatible Performance of Electron Beam Modified and Coated Ti6Al4V Alloy
by Maria Nikolova, Maria Ormanova, Veselina Nikolova and Margarita D. Apostolova
Int. J. Mol. Sci. 2021, 22(12), 6369; https://doi.org/10.3390/ijms22126369 - 14 Jun 2021
Cited by 9 | Viewed by 2991
Abstract
Vacuum cathodic arc TiN coatings with overlaying TiO2 film were deposited on polished and surface roughened by electron beam modification (EBM) Ti6Al4V alloy. The substrate microtopography consisted of long grooves formed by the liner scan of the electron beam with appropriate frequencies [...] Read more.
Vacuum cathodic arc TiN coatings with overlaying TiO2 film were deposited on polished and surface roughened by electron beam modification (EBM) Ti6Al4V alloy. The substrate microtopography consisted of long grooves formed by the liner scan of the electron beam with appropriate frequencies (500 (AR500) and 850 (AR850) Hz). EBM transformed the α + β Ti6Al4V mixed structure into a single α’-martensite phase. Тhe gradient TiN/TiO2 films deposited on mechanically polished (AR) and EBM (AR500 and AR850) alloys share the same surface chemistry and composition (almost stoichiometric TiN, anatase and rutile in different ratios) but exhibit different topographies (Sa equal to approximately 0.62, 1.73, and 1.08 μm, respectively) over areas of 50 × 50 μm. Although the nanohardness of the coatings on AR500 and AR850 alloy (approximately 10.45 and 9.02 GPa, respectively) was lower than that measured on the film deposited on AR alloy (about 13.05 GPa), the hybrid surface treatment offered improvement in critical adhesive loads, coefficient of friction, and wear-resistance of the surface. In phosphate buffer saline, all coated samples showed low corrosion potentials and passivation current densities, confirming their good corrosion protection. The coated EBM samples cultured with human osteoblast-like MG63 cells demonstrated increased cell attachment, viability, and bone mineralization activity especially for the AR500-coated alloy, compared to uncoated polished alloy. The results underline the synergetic effect between the sub-micron structure and composition of TiN/TiO2 coating and microarchitecture obtained by EBM. Full article
(This article belongs to the Special Issue Biomaterials for Bone Tissue Engineering 2.0)
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14 pages, 9278 KiB  
Article
Decellularized Cartilage Extracellular Matrix Incorporated Silk Fibroin Hybrid Scaffolds for Endochondral Ossification Mediated Bone Regeneration
by Vivek Jeyakumar, Nedaa Amraish, Eugenia Niculescu-Morsza, Christoph Bauer, Dieter Pahr and Stefan Nehrer
Int. J. Mol. Sci. 2021, 22(8), 4055; https://doi.org/10.3390/ijms22084055 - 14 Apr 2021
Cited by 10 | Viewed by 2427
Abstract
Tissue engineering strategies promote bone regeneration for large bone defects by stimulating the osteogenesis route via intramembranous ossification in engineered grafts, which upon implantation are frequently constrained by insufficient integration and functional anastomosis of vasculature from the host tissue. In this study, we [...] Read more.
Tissue engineering strategies promote bone regeneration for large bone defects by stimulating the osteogenesis route via intramembranous ossification in engineered grafts, which upon implantation are frequently constrained by insufficient integration and functional anastomosis of vasculature from the host tissue. In this study, we developed a hybrid biomaterial incorporating decellularized cartilage extracellular matrix (CD-ECM) as a template and silk fibroin (SF) as a carrier to assess the bone regeneration capacity of bone marrow-derived mesenchymal stem cells (hBMSC’s) via the endochondral ossification (ECO) route. hBMSC’s were primed two weeks for chondrogenesis, followed by six weeks for hypertrophy onto hybrid CD-ECM/SF or SF alone scaffolds and evaluated for the mineralized matrix formation in vitro. Calcium deposition biochemically determined increased significantly from 4-8 weeks in both SF and CD-ECM/SF constructs, and retention of sGAG’s were observed only in CD-ECM/SF constructs. SEM/EDX revealed calcium and phosphate crystal localization by hBMSC’s under all conditions. Compressive modulus reached a maximum of 40 KPa after eight weeks of hypertrophic induction. μCT scanning at eight weeks indicated a cloud of denser minerals in groups after hypertrophic induction in CD-ECM/SF constructs than SF constructs. Gene expression by RT-qPCR revealed that hBMSC’s expressed hypertrophic markers VEGF, COL10, RUNX2, but the absence of early hypertrophic marker ChM1 and later hypertrophic marker TSBS1 and the presence of osteogenic markers ALPL, IBSP, OSX under all conditions. Our data indicate a new method to prime hBMSC’S into the late hypertrophic stage in vitro in mechanically stable constructs for ECO-mediated bone tissue regeneration. Full article
(This article belongs to the Special Issue Biomaterials for Bone Tissue Engineering 2.0)
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17 pages, 3426 KiB  
Article
The Effect of Pore Size Distribution and l-Lysine Modified Apatite Whiskers (HAP) on Osteoblasts Response in PLLA/HAP Foam Scaffolds Obtained in the Thermally Induced Phase Separation Process
by Konrad Szustakiewicz, Marcin Włodarczyk, Małgorzata Gazińska, Karolina Rudnicka, Przemysław Płociński, Patrycja Szymczyk-Ziółkowska, Grzegorz Ziółkowski, Monika Biernat, Katarzyna Sieja, Michał Grzymajło, Piotr Jóźwiak, Sylwia Michlewska and Andrzej W. Trochimczuk
Int. J. Mol. Sci. 2021, 22(7), 3607; https://doi.org/10.3390/ijms22073607 - 30 Mar 2021
Cited by 12 | Viewed by 2821
Abstract
In this research, we prepared foam scaffolds based on poly(l-lactide) (PLLA) and apatite whiskers (HAP) using thermally induced phase separation technique supported by the salt leaching process (TIPS-SL). Using sodium chloride having a size of (a) 150–315 μm, (b) 315–400 μm, [...] Read more.
In this research, we prepared foam scaffolds based on poly(l-lactide) (PLLA) and apatite whiskers (HAP) using thermally induced phase separation technique supported by the salt leaching process (TIPS-SL). Using sodium chloride having a size of (a) 150–315 μm, (b) 315–400 μm, and (c) 500–600 μm, three types of foams with different pore sizes have been obtained. Internal structure of the obtained materials has been investigated using SEM as well as μCT. The materials have been studied by means of porosity, density, and compression tests. As the most promising, the composite prepared with salt size of 500–600 μm was prepared also with the l-lysine modified apatite. The osteoblast hFOB 1.19 cell response for the scaffolds was also investigated by means of cell viability, proliferation, adhesion/penetration, and biomineralization. Direct contact cytotoxicity assay showed the cytocompatibility of the scaffolds. All types of foam scaffolds containing HAP whiskers, regardless the pore size or l-lysine modification induced significant stimulatory effect on the cal-cium deposits formation in osteoblasts. The PLLA/HAP scaffolds modified with l-lysine stimulated hFOB 1.19 osteoblasts proliferation. Compared to the scaffolds with smaller pores (150–315 µm and 315–400 µm), the PLLA/HAP foams with large pores (500–600 µm) promoted more effective ad-hesion of osteoblasts to the surface of the biomaterial. Full article
(This article belongs to the Special Issue Biomaterials for Bone Tissue Engineering 2.0)
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22 pages, 15444 KiB  
Article
Ex Vivo and In Vivo Analyses of Novel 3D-Printed Bone Substitute Scaffolds Incorporating Biphasic Calcium Phosphate Granules for Bone Regeneration
by Franciska Oberdiek, Carlos Ivan Vargas, Patrick Rider, Milijana Batinic, Oliver Görke, Milena Radenković, Stevo Najman, Jose Manuel Baena, Ole Jung and Mike Barbeck
Int. J. Mol. Sci. 2021, 22(7), 3588; https://doi.org/10.3390/ijms22073588 - 30 Mar 2021
Cited by 8 | Viewed by 4590
Abstract
(1) Background: The aim of this study was examining the ex vivo and in vivo properties of a composite made from polycaprolactone (PCL) and biphasic calcium phosphate (BCP) (synprint, ScientiFY GmbH) fabricated via fused deposition modelling (FDM); (2) Methods: Scaffolds were tested ex [...] Read more.
(1) Background: The aim of this study was examining the ex vivo and in vivo properties of a composite made from polycaprolactone (PCL) and biphasic calcium phosphate (BCP) (synprint, ScientiFY GmbH) fabricated via fused deposition modelling (FDM); (2) Methods: Scaffolds were tested ex vivo for their mechanical properties using porous and solid designs. Subcutaneous implantation model analyzed the biocompatibility of PCL + BCP and PCL scaffolds. Calvaria implantation model analyzed the osteoconductive properties of PCL and PCL + BCP scaffolds compared to BCP as control group. Established histological, histopathological and histomorphometrical methods were performed to evaluate new bone formation.; (3) Results Mechanical testing demonstrated no significant differences between PCL and PCL + BCP for both designs. Similar biocompatibility was observed subcutaneously for PCL and PCL + BCP scaffolds. In the calvaria model, new bone formation was observed for all groups with largest new bone formation in the BCP group, followed by the PCL + BCP group, and the PCL group. This finding was influenced by the initial volume of biomaterial implanted and remaining volume after 90 days. All materials showed osteoconductive properties and PCL + BCP tailored the tissue responses towards higher cellular biodegradability. Moreover, this material combination led to a reduced swelling in PCL + BCP; (4) Conclusions: Altogether, the results show that the newly developed composite is biocompatible and leads to successful osteoconductive bone regeneration. The new biomaterial combines the structural stability provided by PCL with bioactive characteristics of BCP-based BSM. 3D-printed BSM provides an integration behavior in accordance with the concept of guided bone regeneration (GBR) by directing new bone growth for proper function and restoration. Full article
(This article belongs to the Special Issue Biomaterials for Bone Tissue Engineering 2.0)
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20 pages, 7187 KiB  
Article
The Marine Polysaccharide Ulvan Confers Potent Osteoinductive Capacity to PCL-Based Scaffolds for Bone Tissue Engineering Applications
by Stefanos Kikionis, Efstathia Ioannou, Eleni Aggelidou, Leto-Aikaterini Tziveleka, Efterpi Demiri, Athina Bakopoulou, Spiros Zinelis, Aristeidis Kritis and Vassilios Roussis
Int. J. Mol. Sci. 2021, 22(6), 3086; https://doi.org/10.3390/ijms22063086 - 17 Mar 2021
Cited by 18 | Viewed by 2456
Abstract
Hybrid composites of synthetic and natural polymers represent materials of choice for bone tissue engineering. Ulvan, a biologically active marine sulfated polysaccharide, is attracting great interest in the development of novel biomedical scaffolds due to recent reports on its osteoinductive properties. Herein, a [...] Read more.
Hybrid composites of synthetic and natural polymers represent materials of choice for bone tissue engineering. Ulvan, a biologically active marine sulfated polysaccharide, is attracting great interest in the development of novel biomedical scaffolds due to recent reports on its osteoinductive properties. Herein, a series of hybrid polycaprolactone scaffolds containing ulvan either alone or in blends with κ-carrageenan and chondroitin sulfate was prepared and characterized. The impact of the preparation methodology and the polysaccharide composition on their morphology, as well as on their mechanical, thermal, water uptake and porosity properties was determined, while their osteoinductive potential was investigated through the evaluation of cell adhesion, viability, and osteogenic differentiation of seeded human adipose-derived mesenchymal stem cells. The results verified the osteoinductive ability of ulvan, showing that its incorporation into the polycaprolactone matrix efficiently promoted cell attachment and viability, thus confirming its potential in the development of biomedical scaffolds for bone tissue regeneration applications. Full article
(This article belongs to the Special Issue Biomaterials for Bone Tissue Engineering 2.0)
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15 pages, 8465 KiB  
Article
Osteoclastogenic Potential of Tissue-Engineered Periosteal Sheet: Effects of Culture Media on the Ability to Recruit Osteoclast Precursors
by Kohya Uematsu, Takashi Ushiki, Hajime Ishiguro, Riuko Ohashi, Suguru Tamura, Mari Watanabe, Yoko Fujimoto, Masaki Nagata, Yoichi Ajioka and Tomoyuki Kawase
Int. J. Mol. Sci. 2021, 22(4), 2169; https://doi.org/10.3390/ijms22042169 - 22 Feb 2021
Cited by 1 | Viewed by 2360
Abstract
Cell culture media influence the characteristics of human osteogenic periosteal sheets. We have previously found that a stem cell medium facilitates growth and collagen matrix formation in vitro and osteogenesis in vivo. However, it has not yet been demonstrated which culture medium is [...] Read more.
Cell culture media influence the characteristics of human osteogenic periosteal sheets. We have previously found that a stem cell medium facilitates growth and collagen matrix formation in vitro and osteogenesis in vivo. However, it has not yet been demonstrated which culture medium is superior for osteoclastogenesis, a prerequisite for reconstruction of normal bone metabolic basis. To address this question, we compared chemotaxis and osteoclastogenesis in tissue-engineered periosteal sheets (TPSs) prepared with two types of culture media. Periosteal tissues obtained from adult volunteers were expanded with the conventional Medium 199 or with the stem cell medium, MesenPRO. Hematopoietic enhanced-green-fluorescent-protein (EGFP)-nude mice were prepared by γ-irradiation of Balb/c nu/nu mice and subsequent transplantation of bone marrow cells from CAG-EGFP C57BL/6 mice. TPSs were implanted subcutaneously into the chimeric mice and retrieved after intervals for immunohistopathological examination. EGFP+ cells were similarly recruited to the implantation site in both the TPSs prepared, whereas the distribution of CD11b+ cells was significantly lower in the TPS prepared with the stem cell medium. Instead, osteoclastogenesis was higher in the TPS prepared with the stem cell medium than in the one prepared with the conventional medium. These findings suggest that the stem cell medium is preferable for the preparation of more functional TPSs. Full article
(This article belongs to the Special Issue Biomaterials for Bone Tissue Engineering 2.0)
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19 pages, 5116 KiB  
Article
Zoledronic Acid-Loaded β-TCP Inhibits Tumor Proliferation and Osteoclast Activation: Development of a Functional Bone Substitute for an Efficient Osteosarcoma Treatment
by Yuka Kameda, Mamoru Aizawa, Taira Sato and Michiyo Honda
Int. J. Mol. Sci. 2021, 22(4), 1889; https://doi.org/10.3390/ijms22041889 - 14 Feb 2021
Cited by 10 | Viewed by 2307
Abstract
Osteosarcoma has a poor survival rate due to relapse and metastasis. Zoledronic acid (ZOL), an anti-resorptive and anti-tumor agent, is used for treating osteosarcoma. Delivery of ZOL to the target region is difficult due to its high binding affinity to bone minerals. This [...] Read more.
Osteosarcoma has a poor survival rate due to relapse and metastasis. Zoledronic acid (ZOL), an anti-resorptive and anti-tumor agent, is used for treating osteosarcoma. Delivery of ZOL to the target region is difficult due to its high binding affinity to bone minerals. This study developed a novel treatment for osteosarcoma by delivering ZOL to the target region locally and sustainably. In this study, we fabricated a novel bone substitute by loading ZOL on β-tricalcium phosphate (β-TCP). The ZOL-loaded β-TCP (ZOL/β-TCP) would be expected to express the inhibitory effects via both bound-ZOL (bound to β-TCP) and free-ZOL (release from ZOL/β-TCP). To explore the ability to release ZOL from the ZOL/β-TCP, the amount of released ZOL was measured. The released profile indicates that a small amount of ZOL was released, and most of it remained on the β-TCP. Our data showed that ZOL/β-TCP could successfully express the effects of ZOL via both bound-ZOL and free-ZOL. In addition, we examined the biological effects of bound/free-ZOL using osteosarcoma and osteoclasts (target cells). The results showed that two states of ZOL (bound/free) inhibit target cell activities. As a result, ZOL/β-TCP is a promising candidate for application as a novel bone substitute. Full article
(This article belongs to the Special Issue Biomaterials for Bone Tissue Engineering 2.0)
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Review

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16 pages, 2590 KiB  
Review
Combining Biocompatible and Biodegradable Scaffolds and Cold Atmospheric Plasma for Chronic Wound Regeneration
by Steffen Emmert, Sven Pantermehl, Aenne Foth, Janine Waletzko-Hellwig, Georg Hellwig, Rainer Bader, Sabine Illner, Niels Grabow, Sander Bekeschus, Klaus-Dieter Weltmann, Ole Jung and Lars Boeckmann
Int. J. Mol. Sci. 2021, 22(17), 9199; https://doi.org/10.3390/ijms22179199 - 25 Aug 2021
Cited by 8 | Viewed by 3188
Abstract
Skin regeneration is a quite complex process. Epidermal differentiation alone takes about 30 days and is highly regulated. Wounds, especially chronic wounds, affect 2% to 3% of the elderly population and comprise a heterogeneous group of diseases. The prevailing reasons to develop skin [...] Read more.
Skin regeneration is a quite complex process. Epidermal differentiation alone takes about 30 days and is highly regulated. Wounds, especially chronic wounds, affect 2% to 3% of the elderly population and comprise a heterogeneous group of diseases. The prevailing reasons to develop skin wounds include venous and/or arterial circulatory disorders, diabetes, or constant pressure to the skin (decubitus). The hallmarks of modern wound treatment include debridement of dead tissue, disinfection, wound dressings that keep the wound moist but still allow air exchange, and compression bandages. Despite all these efforts there is still a huge treatment resistance and wounds will not heal. This calls for new and more efficient treatment options in combination with novel biocompatible skin scaffolds. Cold atmospheric pressure plasma (CAP) is such an innovative addition to the treatment armamentarium. In one CAP application, antimicrobial effects, wound acidification, enhanced microcirculations and cell stimulation can be achieved. It is evident that CAP treatment, in combination with novel bioengineered, biocompatible and biodegradable electrospun scaffolds, has the potential of fostering wound healing by promoting remodeling and epithelialization along such temporarily applied skin replacement scaffolds. Full article
(This article belongs to the Special Issue Biomaterials for Bone Tissue Engineering 2.0)
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