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Bone Regeneration Materials
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Bone Regeneration Materials

A special issue of Materials (ISSN 1996-1944). This special issue belongs to the section "Biomaterials".

Deadline for manuscript submissions: closed (30 September 2021) | Viewed by 20129

Special Issue Editors

Dr. Andrea Ewald

E-Mail Website
Guest Editor
University Hospital Würzburg, Dept of Functional Materials in Medicine and Dentistry, Pleicherwall 2, 97070 Würzburg, Germany
Interests: antimicrobial materials; in vivo implantation analysis; cell–material interaction
Dr. Elke Vorndran

E-Mail Website
Guest Editor
University Hospital Würzburg, Dept of Functional Materials in Medicine and Dentistry, Pleicherwall 2, 97070 Würzburg, Germany
Interests: 3D printing; patient-specific bone implants; degradable bone cements; calcium and magnesium phospates

Special Issue Information

Dear colleagues,

In a constantly aging population, the need for bone regeneration materials is rising, and alternatives to autologous bone graft materials need to be developed. Depending on the localization of the trauma, the requirements of the material must be addressed, e.g., an implant into loadbearing bones has to be more resilient than a bone replacement material in non-load-bearing regions. There is a wide range of approaches, which address different strategies and materials for bone tissue replacement or regeneration. In this Special Issue, we would like to draw attention to materials which either induce bone regeneration or support bone tissue growth due to their chemical composition, release of drugs, growth factors or transfecting agents, as well as by surface modifications like coatings or structure designs. These materials may be degradable or durable for a longer time and belong to different material classes such as polymers, hydrogels, ceramics, and metals, as well as to composite materials thereof.

Therefore, the scope of the Special Issue “Bone Regeneration Materials” is to bring together a broad overview of the latest developments in this field in the form of original high-quality research papers and short communications covering the most recent advances. It is our pleasure to invite you to submit a manuscript for this Special Issue and open your valuable research to the community.

Dr. Andrea Ewald
Dr. Elke Vorndran
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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. Materials is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). 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

  • Bone regeneration
  • Osteoinduction
  • Osteoconduction
  • Bone implants
  • Coatings
  • Growth factors
  • Bone morphogenic proteins
  • Ceramics
  • Polymers
  • Hydrogels
  • Metals

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Published Papers (7 papers)

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Research

11 pages, 2435 KiB  
Article
Staged Sinus Floor Elevation Using Novel Low-Crystalline Carbonate Apatite Granules: Prospective Results after 3-Year Functional Loading
by Yoichiro Ogino, Yasunori Ayukawa, Noriko Tachikawa, Masahiro Shimogishi, Youji Miyamoto, Keiko Kudoh, Naoyuki Fukuda, Kunio Ishikawa and Kiyoshi Koyano
Materials 2021, 14(19), 5760; https://doi.org/10.3390/ma14195760 - 2 Oct 2021
Cited by 10 | Viewed by 2092
Abstract
The aim of this study was to evaluate clinical outcomes of staged sinus floor elevation (SFE) using novel low-crystalline carbonate apatite (CO3Ap) granules. Patients who needed SFE for implant placement were recruited into this clinical trial. A staged procedure (lateral window [...] Read more.
The aim of this study was to evaluate clinical outcomes of staged sinus floor elevation (SFE) using novel low-crystalline carbonate apatite (CO3Ap) granules. Patients who needed SFE for implant placement were recruited into this clinical trial. A staged procedure (lateral window technique using CO3Ap granules, followed by implant placement after 7 ± 2 months) was employed in 13 patients. Bone-height increase and insertion torque values (ITVs) were assessed along with histological evaluation. The survival and success rates of 3-year functioning implants were also evaluated. Mean of bone-height increase after SFE using CO3Ap granules was 7.2 ± 2.5 mm and this increase allowed implant placement in all cases (17 implants). Mean of ITV was 25.1 ± 13.2 Ncm and primary stability was achieved successfully in all cases. Histological analyses revealed mature new bone formation (36.8 ± 17.3%) and residual CO3Ap granules (16.2 ± 10.1%) in the compartment after SFE. The survival and success rates after 3-year functional loading were 100% and no complications were found. These results clearly indicate the clinical usefulness of CO3Ap granules for SFE. Full article
(This article belongs to the Special Issue Bone Regeneration Materials)
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17 pages, 5587 KiB  
Article
In Vitro Investigation on Degradable Mg-Based Biomaterial under the Impact of the Serum Glycoprotein Fetuin
by Heike Helmholz, Blessing Adejube, Bérengère Luthringer-Feyerabend and Regine Willumeit-Römer
Materials 2021, 14(17), 5005; https://doi.org/10.3390/ma14175005 - 1 Sep 2021
Cited by 4 | Viewed by 2022
Abstract
Biomedical applications of magnesium (Mg) and its alloys are generally dependent on their degradation behavior in vivo. Despite its attractive properties, which make Mg suitable for orthopedic applications, the in vivo material-tissue (bone, blood, and lymph tissues) interaction is not yet fully understood. [...] Read more.
Biomedical applications of magnesium (Mg) and its alloys are generally dependent on their degradation behavior in vivo. Despite its attractive properties, which make Mg suitable for orthopedic applications, the in vivo material-tissue (bone, blood, and lymph tissues) interaction is not yet fully understood. To investigate the influence of major serum proteins on the degradation, this study focused on fetuin, which is one of the major non-collagenous plasma proteins and which is essential for biomineralization. This study used a physiological setup to investigate the influence of fetuin on the degradation behavior of pure Mg in the presence of calcium (Ca). Extruded pure Mg samples were immersed under cell culture conditions in Hank’s balanced salt solution (HBSS) under defined Ca regimes. The results showed a significant decrease in the degradation rate (DR) when both fetuin and Ca were present in an immersion medium as compared to media where they were not simultaneously present. A possible reason for this behavior was the forming of a dense, protein-degradation products protection barrier at the material surface. Furthermore, the limitation of freely available Ca might be a reason for a decreased degradation. The cultivation of primary osteoblasts (pOB) was possible at the fetuin-coated Mg-surface without additional serum supplementation. Full article
(This article belongs to the Special Issue Bone Regeneration Materials)
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20 pages, 3799 KiB  
Article
Modeling of the Human Bone Environment: Mechanical Stimuli Guide Mesenchymal Stem Cell–Extracellular Matrix Interactions
by Ana Rita Pereira, Andreas Lipphaus, Mert Ergin, Sahar Salehi, Dominic Gehweiler, Maximilian Rudert, Jan Hansmann and Marietta Herrmann
Materials 2021, 14(16), 4431; https://doi.org/10.3390/ma14164431 - 7 Aug 2021
Cited by 18 | Viewed by 3647
Abstract
In bone tissue engineering, the design of in vitro models able to recreate both the chemical composition, the structural architecture, and the overall mechanical environment of the native tissue is still often neglected. In this study, we apply a bioreactor system where human [...] Read more.
In bone tissue engineering, the design of in vitro models able to recreate both the chemical composition, the structural architecture, and the overall mechanical environment of the native tissue is still often neglected. In this study, we apply a bioreactor system where human bone-marrow hMSCs are seeded in human femoral head-derived decellularized bone scaffolds and subjected to dynamic culture, i.e., shear stress induced by continuous cell culture medium perfusion at 1.7 mL/min flow rate and compressive stress by 10% uniaxial load at 1 Hz for 1 h per day. In silico modeling revealed that continuous medium flow generates a mean shear stress of 8.5 mPa sensed by hMSCs seeded on 3D bone scaffolds. Experimentally, both dynamic conditions improved cell repopulation within the scaffold and boosted ECM production compared with static controls. Early response of hMSCs to mechanical stimuli comprises evident cell shape changes and stronger integrin-mediated adhesion to the matrix. Stress-induced Col6 and SPP1 gene expression suggests an early hMSC commitment towards osteogenic lineage independent of Runx2 signaling. This study provides a foundation for exploring the early effects of external mechanical stimuli on hMSC behavior in a biologically meaningful in vitro environment, opening new opportunities to study bone development, remodeling, and pathologies. Full article
(This article belongs to the Special Issue Bone Regeneration Materials)
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18 pages, 3769 KiB  
Article
Biomimetic Calcium Phosphate Coatings for Bioactivation of Titanium Implant Surfaces: Methodological Approach and In Vitro Evaluation of Biocompatibility
by Thomas Kreller, Franziska Sahm, Rainer Bader, Aldo R. Boccaccini, Anika Jonitz-Heincke and Rainer Detsch
Materials 2021, 14(13), 3516; https://doi.org/10.3390/ma14133516 - 24 Jun 2021
Cited by 19 | Viewed by 2931
Abstract
Ti6Al4V as a common implant material features good mechanical properties and corrosion resistance. However, untreated, it lacks bioactivity. In contrast, coatings with calcium phosphates (CaP) were shown to improve cell–material interactions in bone tissue engineering. Therefore, this work aimed to investigate how to [...] Read more.
Ti6Al4V as a common implant material features good mechanical properties and corrosion resistance. However, untreated, it lacks bioactivity. In contrast, coatings with calcium phosphates (CaP) were shown to improve cell–material interactions in bone tissue engineering. Therefore, this work aimed to investigate how to tailor biomimetic CaP coatings on Ti6Al4V substrates using modified biomimetic calcium phosphate (BCP) coating solutions. Furthermore, the impact of substrate immersion in a 1 M alkaline CaCl2 solution (pH = 10) on subsequent CaP coating formation was examined. CaP coatings were characterized via scanning electron microscopy, x-ray diffraction, energy-dispersive x-ray spectroscopy, and laser-scanning microscope. Biocompatibility of coatings was carried out with primary human osteoblasts analyzing cell morphology, proliferation, collagen type 1, and interleukin 6 and 8 release. Results indicate a successful formation of low crystalline hydroxyapatite (HA) on top of every sample after immersion in each BCP coating solution after 14 days. Furthermore, HA coating promoted cell proliferation and reduced the concentration of interleukins compared to the uncoated surface, assuming increased biocompatibility. Full article
(This article belongs to the Special Issue Bone Regeneration Materials)
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20 pages, 56417 KiB  
Article
Experimental Drillable Magnesium Phosphate Cement Is a Promising Alternative to Conventional Bone Cements
by Philipp Heilig, Phoebe Sandner, Martin Cornelius Jordan, Rafael Gregor Jakubietz, Rainer Heribert Meffert, Uwe Gbureck and Stefanie Hoelscher-Doht
Materials 2021, 14(8), 1925; https://doi.org/10.3390/ma14081925 - 12 Apr 2021
Cited by 11 | Viewed by 2390
Abstract
Clinically used mineral bone cements lack high strength values, absorbability and drillability. Therefore, magnesium phosphate cements have recently received increasing attention as they unify a high mechanical performance with presumed degradation in vivo. To obtain a drillable cement formulation, farringtonite (Mg3(PO [...] Read more.
Clinically used mineral bone cements lack high strength values, absorbability and drillability. Therefore, magnesium phosphate cements have recently received increasing attention as they unify a high mechanical performance with presumed degradation in vivo. To obtain a drillable cement formulation, farringtonite (Mg3(PO4)2) and magnesium oxide (MgO) were modified with the setting retardant phytic acid (C6H18O24P6). In a pre-testing series, 13 different compositions of magnesium phosphate cements were analyzed concentrating on the clinical demands for application. Of these 13 composites, two cement formulations with different phytic acid content (22.5 wt% and 25 wt%) were identified to meet clinical demands. Both formulations were evaluated in terms of setting time, injectability, compressive strength, screw pullout tests and biomechanical tests in a clinically relevant fracture model. The cements were used as bone filler of a metaphyseal bone defect alone, and in combination with screws drilled through the cement. Both formulations achieved a setting time of 5 min 30 s and an injectability of 100%. Compressive strength was shown to be ~12–13 MPa and the overall displacement of the reduced fracture was <2 mm with and without screws. Maximum load until reduced fracture failure was ~2600 N for the cements only and ~3800 N for the combination with screws. Two new compositions of magnesium phosphate cements revealed high strength in clinically relevant biomechanical test set-ups and add clinically desired characteristics to its strength such as injectability and drillability. Full article
(This article belongs to the Special Issue Bone Regeneration Materials)
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21 pages, 2673 KiB  
Article
Tailorable Zinc-Substituted Mesoporous Bioactive Glass/Alginate-Methylcellulose Composite Bioinks
by Vera Guduric, Niall Belton, Richard Frank Richter, Anne Bernhardt, Janina Spangenberg, Chengtie Wu, Anja Lode and Michael Gelinsky
Materials 2021, 14(5), 1225; https://doi.org/10.3390/ma14051225 - 5 Mar 2021
Cited by 31 | Viewed by 3075
Abstract
Bioactive glasses have been used for bone regeneration applications thanks to their excellent osteoconductivity, an osteostimulatory effect, and high degradation rate, releasing biologically active ions. Besides these properties, mesoporous bioactive glasses (MBG) are specific for their highly ordered mesoporous channel structure and high [...] Read more.
Bioactive glasses have been used for bone regeneration applications thanks to their excellent osteoconductivity, an osteostimulatory effect, and high degradation rate, releasing biologically active ions. Besides these properties, mesoporous bioactive glasses (MBG) are specific for their highly ordered mesoporous channel structure and high specific surface area, making them suitable for drug and growth factor delivery. In the present study, calcium (Ca) (15 mol%) in MBG was partially and fully substituted with zinc (Zn), known for its osteogenic and antimicrobial properties. Different MBG were synthesized, containing 0, 5, 10, or 15 mol% of Zn. Up to 7 wt.% of Zn-containing MBG could be mixed into an alginate-methylcellulose blend (algMC) while maintaining rheological properties suitable for 3D printing of scaffolds with sufficient shape fidelity. The suitability of these composites for bioprinting applications has been demonstrated with immortalized human mesenchymal stem cells. Uptake of Ca and phosphorus (P) (phosphate) ions by composite scaffolds was observed, while the released concentration of Zn2+ corresponded to the initial amount of this ion in prepared glasses, suggesting that it can be controlled at the MBG synthesis step. The study introduces a tailorable bioprintable material system suitable for bone tissue engineering applications. Full article
(This article belongs to the Special Issue Bone Regeneration Materials)
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25 pages, 11731 KiB  
Article
In-Vivo Degradation Behavior and Osseointegration of 3D Powder-Printed Calcium Magnesium Phosphate Cement Scaffolds
by Katharina Kowalewicz, Elke Vorndran, Franziska Feichtner, Anja-Christina Waselau, Manuel Brueckner and Andrea Meyer-Lindenberg
Materials 2021, 14(4), 946; https://doi.org/10.3390/ma14040946 - 17 Feb 2021
Cited by 18 | Viewed by 2538
Abstract
Calcium magnesium phosphate cements (CMPCs) are promising bone substitutes and experience great interest in research. Therefore, in-vivo degradation behavior, osseointegration and biocompatibility of three-dimensional (3D) powder-printed CMPC scaffolds were investigated in the present study. The materials Mg225 (Ca0.75Mg2.25(PO4 [...] Read more.
Calcium magnesium phosphate cements (CMPCs) are promising bone substitutes and experience great interest in research. Therefore, in-vivo degradation behavior, osseointegration and biocompatibility of three-dimensional (3D) powder-printed CMPC scaffolds were investigated in the present study. The materials Mg225 (Ca0.75Mg2.25(PO4)2) and Mg225d (Mg225 treated with diammonium hydrogen phosphate (DAHP)) were implanted as cylindrical scaffolds (h = 5 mm, Ø = 3.8 mm) in both lateral femoral condyles in rabbits and compared with tricalcium phosphate (TCP). Treatment with DAHP results in the precipitation of struvite, thus reducing pore size and overall porosity and increasing pressure stability. Over 6 weeks, the scaffolds were evaluated clinically, radiologically, with Micro-Computed Tomography (µCT) and histological examinations. All scaffolds showed excellent biocompatibility. X-ray and in-vivo µCT examinations showed a volume decrease and increasing osseointegration over time. Structure loss and volume decrease were most evident in Mg225. Histologically, all scaffolds degraded centripetally and were completely traversed by new bone, in which the remaining scaffold material was embedded. While after 6 weeks, Mg225d and TCP were still visible as a network, only individual particles of Mg225 were present. Based on these results, Mg225 and Mg225d appear to be promising bone substitutes for various loading situations that should be investigated further. Full article
(This article belongs to the Special Issue Bone Regeneration Materials)
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