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Biomaterials for Bone Tissue Engineering
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Biomaterials for Bone Tissue Engineering

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 (20 October 2018) | Viewed by 87901

Special Issue Editors

Prof. Dr. Maria-Pau Ginebra

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Guest Editor
Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Metallurgical Engineering, Technical University of Catalonia (UPC), Barcelona, Spain
Interests: bioceramics; bone regeneration; calcium phosphate; drug delivery matrices; biomimetic ceramics; tissue engineering; biological interactions of calcium phosphates; osteoinduction
Prof. Reinhard Schnettler

E-Mail Website
Guest Editor
Justus Liebig University of Giessen, 35390 Giessen, Germany
Interests: tissue engineering; cell–material interactions; cell–cell interactions; cell interactions/crosstalk; drug delivery bone substitutes; ossoinduction; osseoconduction; osteogenesis
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
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Sabine Wenisch

E-Mail Website
Guest Editor
Justus-Liebig-University, Giessen, Germany
Interests: biomaterials; bioactivity; biocompatibility; osteoclasts; foreign body giant cells; mesenchymal stromal cells; cell culture; cell differentiation; cell communication

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 analysed 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 analysing 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.

Prof. Maria-Pau Ginebra
Prof. Reinhard Schnettler
Dr. Mike Barbeck
Prof. Sabine Wenisch
Guest Editors

Manuscript Submission Information

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Keywords

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

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Related Special Issue

Published Papers (15 papers)

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15 pages, 4990 KiB  
Article
FK506 Induces Ligand-Independent Activation of the Bone Morphogenetic Protein Pathway and Osteogenesis
by Sreedhara Sangadala, Emily J. Devereaux, Steven M. Presciutti, Scott D. Boden and Nick J. Willett
Int. J. Mol. Sci. 2019, 20(8), 1900; https://doi.org/10.3390/ijms20081900 - 17 Apr 2019
Cited by 14 | Viewed by 5345 | Correction
Abstract
Osteoinductive bone morphogenetic proteins (BMPs), including BMP-2, have a unique capability of mediating bone formation both in orthotopic and ectopic locations. Immunosuppresive macrolides have been shown to potentiate BMP-2 activity through FKBP12, but these have yet to translate to effective osteoinductive therapies. Herein, [...] Read more.
Osteoinductive bone morphogenetic proteins (BMPs), including BMP-2, have a unique capability of mediating bone formation both in orthotopic and ectopic locations. Immunosuppresive macrolides have been shown to potentiate BMP-2 activity through FKBP12, but these have yet to translate to effective osteoinductive therapies. Herein, we show the osteogenic activity of FK506 as a stand-alone agent in direct comparison to BMP-2 both in vitro and in vivo. FK506 was capable of producing stand-alone alkaline phosphatase induction in C2C12 cells comparable to that seen with rhBMP-2. FK506 treatment activated the BMP receptor, as shown by increased pSmad1/5 levels, and produced significantly higher mRNA levels of the early response genes in BMP and TGF-β pathways. Additionally, the FK506 induction of alkaline phosphatase was shown to be resistant to Noggin treatment. In vivo osteogenic activity of FK506 was tested by local delivery on a collagen sponge in an ectopic subcutaneous implantation model in the rat. Dose responses of FK506 showed increasing levels of ectopic mineralization comparable to the mineral volume produced by BMP-2 delivery. These findings suggest that the use of FK506 can enhance osteoblastic differentiation in vitro and can induce mineralization when delivered locally in vivo. Full article
(This article belongs to the Special Issue Biomaterials for Bone Tissue Engineering)
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15 pages, 3417 KiB  
Article
In Vitro Assessment of Bioactive Glass Coatings on Alumina/Zirconia Composite Implants for Potential Use in Prosthetic Applications
by Francesco Baino, Joaquim Minguella-Canela, Feza Korkusuz, Petek Korkusuz, Berna Kankılıç, María Ángeles Montealegre, M. Antonia De los Santos-López and Chiara Vitale-Brovarone
Int. J. Mol. Sci. 2019, 20(3), 722; https://doi.org/10.3390/ijms20030722 - 8 Feb 2019
Cited by 25 | Viewed by 5708
Abstract
Achieving the stable osteointegration of prosthetic implants is one of the great challenges of modern orthopedic surgery. The fixation of ceramic acetabular cups of hip joint prostheses is usually achieved using a metal shell provided with screws or pegs that penetrate into the [...] Read more.
Achieving the stable osteointegration of prosthetic implants is one of the great challenges of modern orthopedic surgery. The fixation of ceramic acetabular cups of hip joint prostheses is usually achieved using a metal shell provided with screws or pegs that penetrate into the host pelvic bone. The deposition of bioactive coatings on the implant surface to be put in contact with bone could be a valuable strategy to promote a more “physiological” osteointegration. In this work, bioactive glass porous coatings were manufactured on the top of alumina/zirconia composite implants by two different methods, i.e., sponge replication and laser cladding. The coated samples underwent immersion studies in Kokubo’s simulated body fluid (SBF) to assess in vitro bioactivity and were found to exhibit an excellent hydroxyapatite-forming ability, which is key to allow bonding to bone. Biological tests using mesenchymal stem and osteoblast-like cells revealed the good biocompatibility of both types of materials. Furthermore, a higher level of mineralization was induced by the sponge-replicated coatings at 10 days. Overall, these results are highly promising and encourage further research on these materials. Full article
(This article belongs to the Special Issue Biomaterials for Bone Tissue Engineering)
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21 pages, 4690 KiB  
Article
The Effect of the Thermosensitive Biodegradable PLGA–PEG–PLGA Copolymer on the Rheological, Structural and Mechanical Properties of Thixotropic Self-Hardening Tricalcium Phosphate Cement
by Lucy Vojtova, Lenka Michlovska, Kristyna Valova, Marek Zboncak, Martin Trunec, Klara Castkova, Milan Krticka, Veronika Pavlinakova, Petr Polacek, Matej Dzurov, Vera Lukasova, Michala Rampichova, Tomas Suchy, Radek Sedlacek, Maria-Pau Ginebra and Edgar B. Montufar
Int. J. Mol. Sci. 2019, 20(2), 391; https://doi.org/10.3390/ijms20020391 - 17 Jan 2019
Cited by 30 | Viewed by 6159
Abstract
The current limitations of calcium phosphate cements (CPCs) used in the field of bone regeneration consist of their brittleness, low injectability, disintegration in body fluids and low biodegradability. Moreover, no method is currently available to measure the setting time of CPCs in correlation [...] Read more.
The current limitations of calcium phosphate cements (CPCs) used in the field of bone regeneration consist of their brittleness, low injectability, disintegration in body fluids and low biodegradability. Moreover, no method is currently available to measure the setting time of CPCs in correlation with the evolution of the setting reaction. The study proposes that it is possible to improve and tune the properties of CPCs via the addition of a thermosensitive, biodegradable, thixotropic copolymer based on poly(lactic acid), poly(glycolic acid) and poly(ethylene glycol) (PLGA–PEG–PLGA) which undergoes gelation under physiological conditions. The setting times of alpha-tricalcium phosphate (α-TCP) mixed with aqueous solutions of PLGA–PEG–PLGA determined by means of time-sweep curves revealed a lag phase during the dissolution of the α-TCP particles. The magnitude of the storage modulus at lag phase depends on the liquid to powder ratio, the copolymer concentration and temperature. A sharp increase in the storage modulus was observed at the time of the precipitation of calcium deficient hydroxyapatite (CDHA) crystals, representing the loss of paste workability. The PLGA–PEG–PLGA copolymer demonstrates the desired pseudoplastic rheological behaviour with a small decrease in shear stress and the rapid recovery of the viscous state once the shear is removed, thus preventing CPC phase separation and providing good cohesion. Preliminary cytocompatibility tests performed on human mesenchymal stem cells proved the suitability of the novel copolymer/α-TCP for the purposes of mini-invasive surgery. Full article
(This article belongs to the Special Issue Biomaterials for Bone Tissue Engineering)
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20 pages, 5218 KiB  
Article
Improved In Vitro Test Procedure for Full Assessment of the Cytocompatibility of Degradable Magnesium Based on ISO 10993-5/-12
by Ole Jung, Ralf Smeets, Philip Hartjen, Reinhard Schnettler, Frank Feyerabend, Martin Klein, Nils Wegner, Frank Walther, Dominic Stangier, Anders Henningsen, Carsten Rendenbach, Max Heiland, Mike Barbeck and Alexander Kopp
Int. J. Mol. Sci. 2019, 20(2), 255; https://doi.org/10.3390/ijms20020255 - 10 Jan 2019
Cited by 70 | Viewed by 7215
Abstract
Magnesium (Mg)-based biomaterials are promising candidates for bone and tissue regeneration. Alloying and surface modifications provide effective strategies for optimizing and tailoring their degradation kinetics. Nevertheless, biocompatibility analyses of Mg-based materials are challenging due to its special degradation mechanism with continuous hydrogen release. [...] Read more.
Magnesium (Mg)-based biomaterials are promising candidates for bone and tissue regeneration. Alloying and surface modifications provide effective strategies for optimizing and tailoring their degradation kinetics. Nevertheless, biocompatibility analyses of Mg-based materials are challenging due to its special degradation mechanism with continuous hydrogen release. In this context, the hydrogen release and the related (micro-) milieu conditions pretend to strictly follow in vitro standards based on ISO 10993-5/-12. Thus, special adaptions for the testing of Mg materials are necessary, which have been described in a previous study from our group. Based on these adaptions, further developments of a test procedure allowing rapid and effective in vitro cytocompatibility analyses of Mg-based materials based on ISO 10993-5/-12 are necessary. The following study introduces a new two-step test scheme for rapid and effective testing of Mg. Specimens with different surface characteristics were produced by means of plasma electrolytic oxidation (PEO) using silicate-based and phosphate-based electrolytes. The test samples were evaluated for corrosion behavior, cytocompatibility and their mechanical and osteogenic properties. Thereby, two PEO ceramics could be identified for further in vivo evaluations. Full article
(This article belongs to the Special Issue Biomaterials for Bone Tissue Engineering)
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18 pages, 5481 KiB  
Article
A Graded Multifunctional Hybrid Scaffold with Superparamagnetic Ability for Periodontal Regeneration
by Simone Sprio, Elisabetta Campodoni, Monica Sandri, Lorenzo Preti, Tobias Keppler, Frank A. Müller, Nicola M. Pugno and Anna Tampieri
Int. J. Mol. Sci. 2018, 19(11), 3604; https://doi.org/10.3390/ijms19113604 - 15 Nov 2018
Cited by 31 | Viewed by 4707
Abstract
The regeneration of dental tissues is a still an unmet clinical need; in fact, no therapies have been completely successful in regenerating dental tissue complexes such as periodontium, which is also due to the lack of scaffolds that are able to guide and [...] Read more.
The regeneration of dental tissues is a still an unmet clinical need; in fact, no therapies have been completely successful in regenerating dental tissue complexes such as periodontium, which is also due to the lack of scaffolds that are able to guide and direct cell fate towards the reconstruction of different mineralized and non-mineralized dental tissues. In this respect, the present work develops a novel multifunctional hybrid scaffold recapitulating the different features of alveolar bone, periodontal ligament, and cementum by integrating the biomineralization process, and tape casting and electrospinning techniques. The scaffold is endowed with a superparamagnetic ability, thanks to the use of a biocompatible, bioactive superparamagnetic apatite phase, as a mineral component that is able to promote osteogenesis and to be activated by remote magnetic signals. The periodontal scaffold was obtained by engineering three different layers, recapitulating the relevant compositional and microstructural features of the target tissues, into a monolithic multifunctional graded device. Physico-chemical, morphological, and ultrastructural analyses, in association with preliminary in vitro investigations carried out with mesenchymal stem cells, confirm that the final scaffold exhibits a good mimicry of the periodontal tissue complex, with excellent cytocompatibility and cell viability, making it very promising for regenerative applications in dentistry. Full article
(This article belongs to the Special Issue Biomaterials for Bone Tissue Engineering)
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16 pages, 3255 KiB  
Article
Design of a 3D BMP-2-Delivering Tannylated PCL Scaffold and Its Anti-Oxidant, Anti-Inflammatory, and Osteogenic Effects In Vitro
by Jae Yong Lee, Hyunwoong Lim, Jae Won Ahn, Dongsik Jang, Seung Hee Lee, Kyeongsoon Park and Sung Eun Kim
Int. J. Mol. Sci. 2018, 19(11), 3602; https://doi.org/10.3390/ijms19113602 - 15 Nov 2018
Cited by 39 | Viewed by 6663
Abstract
In this study, a novel three-dimensional (3D) bone morphogenic protein-2 (BMP-2)-delivering tannylated polycaprolactone (PCL) (BMP-2/tannic acid (TA)/PCL) scaffold with anti-oxidant, anti-inflammatory, and osteogenic activities was fabricated via simple surface coating with TA, followed by the immobilization of BMP-2 on the TA-coated PCL scaffold. [...] Read more.
In this study, a novel three-dimensional (3D) bone morphogenic protein-2 (BMP-2)-delivering tannylated polycaprolactone (PCL) (BMP-2/tannic acid (TA)/PCL) scaffold with anti-oxidant, anti-inflammatory, and osteogenic activities was fabricated via simple surface coating with TA, followed by the immobilization of BMP-2 on the TA-coated PCL scaffold. The BMP-2/TA/PCL scaffold showed controlled and sustained BMP-2 release. It effectively scavenged reactive oxygen species (ROS) in cells, and increased the proliferation of MC3T3-E1 cells pre-treated with hydrogen peroxide (H2O2). Additionally, the BMP-2/TA/PCL scaffold significantly suppressed the mRNA levels of pro-inflammatory cytokines, including matrix metalloproteinases-3 (MMP-3), cyclooxygenase-2 (COX-2), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), in lipopolysaccharide (LPS)-induced MC3T3-E1 cells. Furthermore, it showed outstanding enhancement of the osteogenic activity of MC3T3-E1 cells through increased alkaline phosphatase (ALP) activity and calcium deposition. Our findings demonstrated that the BMP-2/TA/PCL scaffold plays an important role in scavenging ROS, suppressing inflammatory response, and enhancing the osteogenic differentiation of cells. Full article
(This article belongs to the Special Issue Biomaterials for Bone Tissue Engineering)
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19 pages, 3878 KiB  
Article
Effects of a Pasty Bone Cement Containing Brain-Derived Neurotrophic Factor-Functionalized Mesoporous Bioactive Glass Particles on Metaphyseal Healing in a New Murine Osteoporotic Fracture Model
by Vivien Kauschke, Maike Schneider, Annika Jauch, Matthias Schumacher, Marian Kampschulte, Marcus Rohnke, Anja Henss, Coralie Bamberg, Katja Trinkaus, Michael Gelinsky, Christian Heiss and Katrin Susanne Lips
Int. J. Mol. Sci. 2018, 19(11), 3531; https://doi.org/10.3390/ijms19113531 - 9 Nov 2018
Cited by 32 | Viewed by 5125
Abstract
The development of new and better implant materials adapted to osteoporotic bone is still urgently required. Therefore, osteoporotic muscarinic acetylcholine receptor M3 (M3 mAChR) knockout (KO) and corresponding wild type (WT) mice underwent osteotomy in the distal femoral metaphysis. Fracture gaps were filled [...] Read more.
The development of new and better implant materials adapted to osteoporotic bone is still urgently required. Therefore, osteoporotic muscarinic acetylcholine receptor M3 (M3 mAChR) knockout (KO) and corresponding wild type (WT) mice underwent osteotomy in the distal femoral metaphysis. Fracture gaps were filled with a pasty α-tricalcium phosphate (α-TCP)-based hydroxyapatite (HA)-forming bone cement containing mesoporous bioactive CaP-SiO2 glass particles (cement/MBG composite) with or without Brain-Derived Neurotrophic Factor (BDNF) and healing was analyzed after 35 days. Histologically, bone formation was significantly increased in WT mice that received the BDNF-functionalized cement/MBG composite compared to control WT mice without BDNF. Cement/MBG composite without BDNF increased bone formation in M3 mAChR KO mice compared to equally treated WT mice. Mass spectrometric imaging showed that the BDNF-functionalized cement/MBG composite implanted in M3 mAChR KO mice was infiltrated by newly formed tissue. Leukocyte numbers were significantly lower in M3 mAChR KO mice treated with BDNF-functionalized cement/MBG composite compared to controls without BDNF. C-reactive protein (CRP) concentrations were significantly lower in M3 mAChR KO mice that received the cement/MBG composite without BDNF when compared to WT mice treated the same. Whereas alkaline phosphatase (ALP) concentrations in callus were significantly increased in M3 mAChR KO mice, ALP activity was significantly higher in WT mice. Due to a stronger effect of BDNF in non osteoporotic mice, higher BDNF concentrations might be needed for osteoporotic fracture healing. Nevertheless, the BDNF-functionalized cement/MBG composite promoted fracture healing in non osteoporotic bone. Full article
(This article belongs to the Special Issue Biomaterials for Bone Tissue Engineering)
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15 pages, 5967 KiB  
Article
Epigallocatechin Gallate-Modified Gelatins with Different Compositions Alter the Quality of Regenerated Bones
by Eiki Hara, Yoshitomo Honda, Osamu Suzuki, Tomonari Tanaka and Naoyuki Matsumoto
Int. J. Mol. Sci. 2018, 19(10), 3232; https://doi.org/10.3390/ijms19103232 - 19 Oct 2018
Cited by 12 | Viewed by 3396
Abstract
Bone quality is a significant indicator of the result of bone treatments. However, information regarding the quality of regenerated bones is limited. The study investigates the effect of different compositions of vacuum heated epigallocatechin gallate-modified gelatins sponge (vhEGCG-GS) on the quality of regenerated [...] Read more.
Bone quality is a significant indicator of the result of bone treatments. However, information regarding the quality of regenerated bones is limited. The study investigates the effect of different compositions of vacuum heated epigallocatechin gallate-modified gelatins sponge (vhEGCG-GS) on the quality of regenerated bones in critical size defects (9 mm) of rat calvariae. Five different compositions of vhEGCG-GSs containing the same amount of EGCG and different amounts of gelatin were tested. Following four weeks after implantation, the harvested regenerated bones were evaluated by using micro-computed tomography analysis, histological evaluation (hematoxylin-eosin and Villaneueva Goldner staining), picrosirius red-staining with polarized microscopic observation for collagen maturation, and Fourier transform infrared spectroscopy microscopy and imaging analysis for mineral-matrix ratio. The results indicated that increasing content of gelatin in the vhEGCG-GSs promoted bone and osteoid formation but yielded porous bones. Furthermore, tissue mineral density decreased and the maximum mineral-matrix ratio increased. In contrast, vhEGCG-GSs containing smaller amount of gelatin formed mature collagen matrix in the regenerated bones. These results suggest that the alteration of composition of vhEGCG-GSs affected the bone forming capability and quality of regenerated bone and provides valuable insight for the fabrication of new bone substitute materials. Full article
(This article belongs to the Special Issue Biomaterials for Bone Tissue Engineering)
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12 pages, 3415 KiB  
Article
In Vivo Analysis of the Biocompatibility and Macrophage Response of a Non-Resorbable PTFE Membrane for Guided Bone Regeneration
by Tadas Korzinskas, Ole Jung, Ralf Smeets, Sanja Stojanovic, Stevo Najman, Kristina Glenske, Michael Hahn, Sabine Wenisch, Reinhard Schnettler and Mike Barbeck
Int. J. Mol. Sci. 2018, 19(10), 2952; https://doi.org/10.3390/ijms19102952 - 27 Sep 2018
Cited by 60 | Viewed by 6073
Abstract
The use of non-resorbable polytetrafluoroethylene (PTFE) membranes is indicated for the treatment of large, non-self-containing bone defects, or multi-walled defects in the case of vertical augmentations. However, less is known about the molecular basis of the foreign body response to PTFE membranes. In [...] Read more.
The use of non-resorbable polytetrafluoroethylene (PTFE) membranes is indicated for the treatment of large, non-self-containing bone defects, or multi-walled defects in the case of vertical augmentations. However, less is known about the molecular basis of the foreign body response to PTFE membranes. In the present study, the inflammatory tissue responses to a novel high-density PTFE (dPTFE) barrier membrane have preclinically been evaluated using the subcutaneous implantation model in BALB/c mice by means of histopathological and histomorphometrical analysis methods and immunohistochemical detection of M1- and M2-macrophages. A collagen membrane was used as the control material. The results of the present study demonstrate that the tissue response to the dPTFE membrane involves inflammatory macrophages, but comparable cell numbers were also detected in the implant beds of the control collagen membrane, which is known to be biocompatible. Although these data indicate that the analyzed dPTFE membrane is not fully bioinert, but its biocompatibility is comparable to collagen-based membranes. Based on its optimal biocompatibility, the novel dPTFE barrier membrane may optimally support bone healing within the context of guided bone regeneration (GBR). Full article
(This article belongs to the Special Issue Biomaterials for Bone Tissue Engineering)
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17 pages, 3865 KiB  
Article
Two Different Strategies to Enhance Osseointegration in Porous Titanium: Inorganic Thermo-Chemical Treatment Versus Organic Coating by Peptide Adsorption
by Monica Ortiz-Hernandez, Katrin S. Rappe, Meritxell Molmeneu, Carles Mas-Moruno, Jordi Guillem-Marti, Miquel Punset, Cristina Caparros, Jose Calero, Jordi Franch, Mariano Fernandez-Fairen and Javier Gil
Int. J. Mol. Sci. 2018, 19(9), 2574; https://doi.org/10.3390/ijms19092574 - 30 Aug 2018
Cited by 20 | Viewed by 4551
Abstract
In this study, highly-interconnected porous titanium implants were produced by powder sintering with different porous diameters and open interconnectivity. The actual foams were produced using high cost technologies: Chemical Vapor Deposition (CVD), Physical Vapor Deposition (PVD), and spark plasma sintering, and the porosity [...] Read more.
In this study, highly-interconnected porous titanium implants were produced by powder sintering with different porous diameters and open interconnectivity. The actual foams were produced using high cost technologies: Chemical Vapor Deposition (CVD), Physical Vapor Deposition (PVD), and spark plasma sintering, and the porosity and/or interconnection was not optimized. The aim was to generate a bioactive surface on foams using two different strategies, based on inorganic thermo-chemical treatment and organic coating by peptide adsorption, to enhance osseointegration. Porosity was produced using NaCl as a space holder and polyethyleneglicol as a binder phase. Static and fatigue tests were performed in order to determine mechanical behaviors. Surface bioactivation was performed using a thermo-chemical treatment or by chemical adsorption with peptides. Osteoblast-like cells were cultured and cytotoxicity was measured. Bioactivated scaffolds and a control were implanted in the tibiae of rabbits. Histomorphometric evaluation was performed at 4 weeks after implantation. Interconnected porosity was 53% with an average diameter of 210 µm and an elastic modulus of around 1 GPa with good mechanical properties. The samples presented cell survival values close to 100% of viability. Newly formed bone was observed inside macropores, through interconnected porosity, and on the implant surface. Successful bone colonization of inner structure (40%) suggested good osteoconductive capability of the implant. Bioactivated foams showed better results than non-treated ones, suggesting both bioactivation strategies induce osteointegration capability. Full article
(This article belongs to the Special Issue Biomaterials for Bone Tissue Engineering)
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18 pages, 10241 KiB  
Article
Bone Regeneration Using Adipose-Derived Stem Cells in Injectable Thermo-Gelling Hydrogel Scaffold Containing Platelet-Rich Plasma and Biphasic Calcium Phosphate
by Han Tsung Liao, Ming-Jin Tsai, Manuri Brahmayya and Jyh-Ping Chen
Int. J. Mol. Sci. 2018, 19(9), 2537; https://doi.org/10.3390/ijms19092537 - 27 Aug 2018
Cited by 45 | Viewed by 6253
Abstract
For bone regeneration, a biocompatible thermo-gelling hydrogel, hyaluronic acid-g-chitosan-g-poly(N-isopropylacrylamide) (HA-CPN) was used as a three-dimensional organic gel matrix for entrapping rabbit adipose-derived stem cells (rASCs). Biphasic calcium phosphate (BCP) ceramic microparticles were embedded within the gel matrix [...] Read more.
For bone regeneration, a biocompatible thermo-gelling hydrogel, hyaluronic acid-g-chitosan-g-poly(N-isopropylacrylamide) (HA-CPN) was used as a three-dimensional organic gel matrix for entrapping rabbit adipose-derived stem cells (rASCs). Biphasic calcium phosphate (BCP) ceramic microparticles were embedded within the gel matrix as a mineralized bone matrix, which was further fortified with platelet-rich plasma (PRP) with osteo-inductive properties. In vitro culture of rASCs in HA-CPN and HA-CPN/PRP/BCP was compared for cell proliferation and osteogenic differentiation. Overall, HA-CPN/PRP/BCP was a better injectable cell carrier for osteogenesis of rASCs with increased cell proliferation rate and alkaline phosphatase activity, enhanced calcium deposition and mineralization of extracellular matrix, and up-regulated expression of genetic markers of osteogenesis. By implanting HA-CPN/PRP/BCP/rASCs constructs in rabbit critical size calvarial bone defects, new bone formation at the defect site was successfully demonstrated from computed tomography, and histological and immunohistochemical analysis. Taken together, by combining PRP and BCP as the osteo-inductive and osteo-conductive factor with HA-CPN, we successfully demonstrated the thermo-gelling composite hydrogel scaffold could promote the osteogenesis of rASCs for bone tissue engineering applications. Full article
(This article belongs to the Special Issue Biomaterials for Bone Tissue Engineering)
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Review

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17 pages, 1114 KiB  
Review
Role of the Complement System in the Response to Orthopedic Biomaterials
by Yvonne Mödinger, Graciosa Q. Teixeira, Cornelia Neidlinger-Wilke and Anita Ignatius
Int. J. Mol. Sci. 2018, 19(11), 3367; https://doi.org/10.3390/ijms19113367 - 27 Oct 2018
Cited by 36 | Viewed by 8799
Abstract
Various synthetic biomaterials are used to replace lost or damaged bone tissue that, more or less successfully, osseointegrate into the bone environment. Almost all biomaterials used in orthopedic medicine activate the host-immune system to a certain degree. The complement system, which is a [...] Read more.
Various synthetic biomaterials are used to replace lost or damaged bone tissue that, more or less successfully, osseointegrate into the bone environment. Almost all biomaterials used in orthopedic medicine activate the host-immune system to a certain degree. The complement system, which is a crucial arm of innate immunity, is rapidly activated by an implanted foreign material into the human body, and it is intensely studied regarding blood-contacting medical devices. In contrast, much less is known regarding the role of the complement system in response to implanted bone biomaterials. However, given the increasing knowledge of the complement regulation of bone homeostasis, regeneration, and inflammation, complement involvement in the immune response following biomaterial implantation into bone appears very likely. Moreover, bone cells can produce complement factors and are target cells of activated complement. Therefore, new bone formation or bone resorption around the implant area might be greatly influenced by the complement system. This review aims to summarize the current knowledge on biomaterial-mediated complement activation, with a focus on materials primarily used in orthopedic medicine. In addition, methods to modify the interactions between the complement system and bone biomaterials are discussed, which might favor osseointegration and improve the functionality of the device. Full article
(This article belongs to the Special Issue Biomaterials for Bone Tissue Engineering)
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35 pages, 3532 KiB  
Review
Additive Manufacturing for Guided Bone Regeneration: A Perspective for Alveolar Ridge Augmentation
by Patrick Rider, Željka Perić Kačarević, Said Alkildani, Sujith Retnasingh, Reinhard Schnettler and Mike Barbeck
Int. J. Mol. Sci. 2018, 19(11), 3308; https://doi.org/10.3390/ijms19113308 - 24 Oct 2018
Cited by 66 | Viewed by 7984
Abstract
Three-dimensional (3D) printing has become an important tool in the field of tissue engineering and its further development will lead to completely new clinical possibilities. The ability to create tissue scaffolds with controllable characteristics, such as internal architecture, porosity, and interconnectivity make it [...] Read more.
Three-dimensional (3D) printing has become an important tool in the field of tissue engineering and its further development will lead to completely new clinical possibilities. The ability to create tissue scaffolds with controllable characteristics, such as internal architecture, porosity, and interconnectivity make it highly desirable in comparison to conventional techniques, which lack a defined structure and repeatability between scaffolds. Furthermore, 3D printing allows for the production of scaffolds with patient-specific dimensions using computer-aided design. The availability of commercially available 3D printed permanent implants is on the rise; however, there are yet to be any commercially available biodegradable/bioresorbable devices. This review will compare the main 3D printing techniques of: stereolithography; selective laser sintering; powder bed inkjet printing and extrusion printing; for the fabrication of biodegradable/bioresorbable bone tissue scaffolds; and, discuss their potential for dental applications, specifically augmentation of the alveolar ridge. Full article
(This article belongs to the Special Issue Biomaterials for Bone Tissue Engineering)
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16 pages, 4226 KiB  
Review
Cellular Mechanisms Responsible for Success and Failure of Bone Substitute Materials
by Tim Rolvien, Mike Barbeck, Sabine Wenisch, Michael Amling and Matthias Krause
Int. J. Mol. Sci. 2018, 19(10), 2893; https://doi.org/10.3390/ijms19102893 - 23 Sep 2018
Cited by 44 | Viewed by 6549
Abstract
Bone grafts, i.e., autologous, allogeneic or synthetic bone substitute materials play an increasing role in reconstructive orthopedic surgery. While the indications and materials differ, it is important to understand the cellular mechanisms regarding their integration and remodeling, which are discussed in this review [...] Read more.
Bone grafts, i.e., autologous, allogeneic or synthetic bone substitute materials play an increasing role in reconstructive orthopedic surgery. While the indications and materials differ, it is important to understand the cellular mechanisms regarding their integration and remodeling, which are discussed in this review article. Osteoconductivity describes the new bone growth on the graft, while osteoinductivity represents the differentiation of undifferentiated cells into bone forming osteoblasts. The best case is that both mechanisms are accompanied by osteogenesis, i.e., bone modeling and remodeling of the graft material. Graft incorporation is mediated by a number of molecular pathways that signal the differentiation and activity of osteoblasts and osteoclasts (e.g., parathyroid hormone (PTH) and receptor activator of nuclear factor κβ ligand (RANKL), respectively). Direct contact of the graft and host bone as well as the presence of a mechanical load are a prerequisite for the successful function of bone grafts. Interestingly, while bone substitutes show good to excellent clinical outcomes, their histological incorporation has certain limits that are not yet completely understood. For instance, clinical studies have shown contrasting results regarding the complete or incomplete resorption and remodeling of allografts and synthetic grafts. In this context, a foreign body response can lead to complete material degradation via phagocytosis, however it may also cause a fibrotic reaction to the bone substitute. Finally, the success of bone graft incorporation is also limited by other factors, including the bone remodeling capacities of the host, the material itself (e.g., inadequate resorption, toxicity) and the surgical technique or preparation of the graft. Full article
(This article belongs to the Special Issue Biomaterials for Bone Tissue Engineering)
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2 pages, 157 KiB  
Correction
Correction: Sangadala, S. et al. FK506 Induces Ligand-Independent Activation of the Bone Morphogenetic Protein Pathway and Osteogenesis. Int. J. Mol. Sci. 2019, 20, 1900
by Sreedhara Sangadala, Emily J. Devereaux, Steven M. Presciutti, Scott D. Boden and Nick J. Willett
Int. J. Mol. Sci. 2020, 21(17), 6287; https://doi.org/10.3390/ijms21176287 - 31 Aug 2020
Cited by 1 | Viewed by 1554
Abstract
The authors wish to make the following corrections to this paper [...] Full article
(This article belongs to the Special Issue Biomaterials for Bone Tissue Engineering)
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