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Special Issue "Bone Substitute Materials"

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

Deadline for manuscript submissions: closed (30 April 2018)

Special Issue Editor

Guest Editor
Assoc. Prof. Steven J. Eppell

Case Western Reserve University, Department of Biomedical Engineering, Cleveland, United States
Website | E-Mail
Interests: Biomimetic Biomaterial Design and Synthesis, 3D Nanoscale Imaging and Force Measurement

Special Issue Information

Dear Colleagues,

This issue focuses on the design, synthesis and/or evaluation of bone substitute materials. Appropriate submissions use information about the nanoscale structure of natural bone in a way that allows the synthetic material to duplicate biomechanical and/or cellular behavior of the natural system.  Submissions describing attempts to duplicate collagen structures, mineral apatites, ground substance and their hierarchical juxstapositions as found in bone are welcome.   All submissions must clearly connect material composition and/or structure with the desired mechanical and/or biological function of the biomaterial.  Authors are encouraged to include a section in each manuscript devoted to explaining how the materials science and engineering aspects of the work are related to solving an outstanding clinical problem.

It is my pleasure to invite you to submit a manuscript for this Special Issue. Full papers, communications, and reviews are all welcome.

Assoc. Prof. Steven J. Eppell
Guest Editor

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 papers will be 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 monthly 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 1600 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
  • biomaterial
  • collagen
  • mineral
  • ground substance
  • biomechanics
  • remodelling
  • biocompatible
  • osteoblast
  • osteoclast

Published Papers (9 papers)

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Research

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Open AccessArticle A Novel Multiscale Mathematical Model for Building Bone Substitute Materials for Children
Materials 2018, 11(6), 1045; https://doi.org/10.3390/ma11061045
Received: 30 April 2018 / Revised: 10 May 2018 / Accepted: 12 May 2018 / Published: 20 June 2018
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Abstract
Bone is an engineering marvel that achieves a unique combination of stiffness and toughness exceeding that of synthesized materials. In orthopedics, we are currently challenged for the child population that needs a less stiff but a tougher bone substitute than adults. Recent evidence
[...] Read more.
Bone is an engineering marvel that achieves a unique combination of stiffness and toughness exceeding that of synthesized materials. In orthopedics, we are currently challenged for the child population that needs a less stiff but a tougher bone substitute than adults. Recent evidence suggests that the relationship between inter-molecular connections that involve the two main bone building blocks, TropoCollagen molecules (TC) and carbonated Hydroxyapatite (cAp), and bone macroscopic mechanical properties, stiffness and toughness, are key to building bone substitute materials for children. The goal of our study is to establish how inter-molecular connections that occur during bone mineralization are related to macroscopic mechanical properties in child bones. Our aim is to link the biological alterations of the TC-cAp self assembly process happening during bone mineralization to the bone macroscopic mechanical properties’ alterations during aging. To do so, we have developed a multiscale mathematical model that includes collagen cross links (TC–TC interface) from experimental studies of bone samples to forecast bone macroscopic mechanical properties. Our results support that the Young’s modulus cannot be a linear parameter if we want to solve our system. In relation to bone substitute material with innovative properties for children, our results propose values of several biological parameters, such as the number of crystals and their size, and collagen crosslink maturity for the desired bone mechanical competence. Our novel mathematical model combines mineralization and macroscopic mechanical behavior of bone and is a step forward in building mechanically customized biomimetic bone grafts that would fit children’s orthopedic needs. Full article
(This article belongs to the Special Issue Bone Substitute Materials)
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Open AccessArticle Influence of Absorbable Calcium Sulfate-Based Bone Substitute Materials on Human Haemostasis—In Vitro Biological Behavior of Antibiotic Loaded Implants
Materials 2018, 11(6), 935; https://doi.org/10.3390/ma11060935
Received: 20 April 2018 / Revised: 16 May 2018 / Accepted: 30 May 2018 / Published: 1 June 2018
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Abstract
Calcium sulfate (CS) formulations are frequently implanted as antibiotically impregnated bone substitutes in orthopedic and trauma surgery to prevent or treat bone infections. Calcium ions have been discussed as candidates to accelerate blood coagulation. The goal of this study is to evaluate substance-specific
[...] Read more.
Calcium sulfate (CS) formulations are frequently implanted as antibiotically impregnated bone substitutes in orthopedic and trauma surgery to prevent or treat bone infections. Calcium ions have been discussed as candidates to accelerate blood coagulation. The goal of this study is to evaluate substance-specific influences of CS formulations on blood coagulation. Specific ELISAs were conducted to determine markers of activated blood coagulation after incubation of human blood with CS beads. Additionally, wettability with freshly drawn human blood was measured. Three different types of CS bone substitute beads were compared (CS dihydrate with tripalmitin, containing Gentamicin (Herafill®-G: Group A) or Vancomycin (CaSO4-V: Group B); and a CS hemihydrate with Tobramycin (Osteoset®: Group C)). Examinations were performed by ELISA assays for F1+2, FXIIa and C3a. Our results prove that none of the CS preparations accelerated single specific assays for activated coagulation markers. This allows the conclusion that neither Herafill®-G (CaSO4-G) nor CaSO4-V alter haemostasis negatively. Blood samples incubated with Osteoset® display an elevated F1+2-activity. The addition of tripalmitin in Herafill®-G shifts the original into a significantly hydrophobic formulation. This was additionally proven by contact angle examination of the three substances with freshly drawn human blood, showing that acceleration of plasmatic coagulation is hindered by lipids and induced by surface effects caused by presence of rapidly soluble calcium ions in the Osteoset® preparation. Full article
(This article belongs to the Special Issue Bone Substitute Materials)
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Open AccessArticle Histological Evaluation of the Healing Process of Various Bone Graft Materials after Engraftment into the Human Body
Materials 2018, 11(5), 714; https://doi.org/10.3390/ma11050714
Received: 3 April 2018 / Revised: 24 April 2018 / Accepted: 2 May 2018 / Published: 2 May 2018
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Abstract
The purpose of this study was to measure the level of new bone formation induced by various bone graft materials to provide clinicians with more choices. The samples were divided into three groups: group 1 (n = 9: allograft + xenograft, DBX
[...] Read more.
The purpose of this study was to measure the level of new bone formation induced by various bone graft materials to provide clinicians with more choices. The samples were divided into three groups: group 1 (n = 9: allograft + xenograft, DBX®, San Francisco, CA, USA + Bio-Oss®, Princeton, NJ, USA), group 2 (n = 10: xenograft, Bio-Oss®), and group 3 (n = 8: autogenous tooth bone graft, AutoBT®, Korea Tooth Bank, Seoul, Korea). The average duration of evaluation was 9.56, 2.50, and 3.38 months, respectively. A tissue sample was taken from 27 patients during the second implant surgery. New bone formation was measured via histomorphometry, using a charge-coupled device camera, adaptor, and image analysis software. Total bone area, total area, and ((total bone area/total area) × 100) was measured to determine the extent of new bone formation. The mean value of the total bone area was 152,232.63 μm2; the mean value of the total area was 1,153,696.46 μm2; and the mean total bone area/total area ratio was 13.50%. In each comparison, there was no significant difference among the groups; no inflammation or complications were found in any of the groups. AutoBT®, an autogenous tooth bone graft, resulted in a level of bone formation similar to that using allografts and xenografts. Full article
(This article belongs to the Special Issue Bone Substitute Materials)
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Open AccessArticle Synthesis, Characterization and In Vitro Study of Synthetic and Bovine-Derived Hydroxyapatite Ceramics: A Comparison
Materials 2018, 11(3), 333; https://doi.org/10.3390/ma11030333
Received: 18 January 2018 / Revised: 7 February 2018 / Accepted: 20 February 2018 / Published: 25 February 2018
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Abstract
The physicochemical properties and biological behavior of sintered-bovine-derived hydroxyapatite (BHAp) are here reported and compared to commercial synthetic-HAp (CHAp). Dense ceramics were sintered for 2 h and 4 h at 1200 °C to investigate their microstructure–structure–in-vitro behavior relationship for both HAp ceramics. Densification
[...] Read more.
The physicochemical properties and biological behavior of sintered-bovine-derived hydroxyapatite (BHAp) are here reported and compared to commercial synthetic-HAp (CHAp). Dense ceramics were sintered for 2 h and 4 h at 1200 °C to investigate their microstructure–structure–in-vitro behavior relationship for both HAp ceramics. Densification was directly proportional to sintering time, showing a grain coarsening behavior with a greater effect on BHAp. Lattice parameters, crystallite size, cell volume and Ca/P ratio were determined by Rietveld refinement of X-ray diffraction (XRD) patterns using GSAS®. Ionic substitutions (Na+, Mg2+, CO32−) related to BHAp structure were associated with their position changes in the vibrational modes and correlated with the structural parameters obtained from the XRD analysis. Variations in the structural parameters and surface morphology were also evaluated after different soaking periods in simulated body fluid, which is associated with the formation of bone-like apatite layer and thus bioactivity. Mitochondrial activity (MTS) and lactate dehydrogenase (LDH) assays showed that the material released by the ceramics does not induce toxicity after exposure in human fetal osteoblastic (hFOB) cells. Furthermore, no statistically significant differences were found between the HAp obtained from different sources. These results show that BHAp can be used with no restrictions for the same biomedical applications as CHAp. Full article
(This article belongs to the Special Issue Bone Substitute Materials)
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Open AccessArticle Efficacy of Octacalcium Phosphate Collagen Composite for Titanium Dental Implants in Dogs
Materials 2018, 11(2), 229; https://doi.org/10.3390/ma11020229
Received: 9 January 2018 / Revised: 25 January 2018 / Accepted: 30 January 2018 / Published: 2 February 2018
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Abstract
Background: Previous studies showed that octacalcium (OCP) collagen composite (OCP/Col) can be used to repair human jaw bone defects without any associated abnormalities. The present study investigated whether OCP/Col could be applied to dental implant treatment using a dog tooth extraction socket model.
[...] Read more.
Background: Previous studies showed that octacalcium (OCP) collagen composite (OCP/Col) can be used to repair human jaw bone defects without any associated abnormalities. The present study investigated whether OCP/Col could be applied to dental implant treatment using a dog tooth extraction socket model. Methods: The premolars of dogs were extracted; each extraction socket was extended, and titanium dental implants were placed in each socket. OCP/Col was inserted in the space around a titanium dental implant. Autologous bone was used to fill the other sockets, while the untreated socket (i.e., no bone substitute material) served as a control. Three months after the operation, these specimens were analyzed for the osseointegration of each bone substitute material with the surface of the titanium dental implant. Results: In histomorphometric analyses, the peri-implant bone areas (BA%) and bone-implant contact (BIC%) were measured. There was no difference in BA% or BIC% between OCP/Col and autologous bone. Conclusion: These results suggested that OCP/Col could be used for implant treatment as a bone substitute. Full article
(This article belongs to the Special Issue Bone Substitute Materials)
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Open AccessArticle Hydrophilicity, Viscoelastic, and Physicochemical Properties Variations in Dental Bone Grafting Substitutes
Materials 2018, 11(2), 215; https://doi.org/10.3390/ma11020215
Received: 9 January 2018 / Revised: 19 January 2018 / Accepted: 24 January 2018 / Published: 30 January 2018
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Abstract
The indication-oriented Dental Bone Graft Substitutes (DBGS) selection, the correct bone defects classification, and appropriate treatment planning are very crucial for obtaining successful clinical results. However, hydrophilic, viscoelastic, and physicochemical properties’ influence on the DBGS regenerative potential has poorly been studied. For that
[...] Read more.
The indication-oriented Dental Bone Graft Substitutes (DBGS) selection, the correct bone defects classification, and appropriate treatment planning are very crucial for obtaining successful clinical results. However, hydrophilic, viscoelastic, and physicochemical properties’ influence on the DBGS regenerative potential has poorly been studied. For that reason, we investigated the dimensional changes and molecular mobility by Dynamic Mechanical Analysis (DMA) of xenograft (cerabone®), synthetic (maxresorb®), and allograft (maxgraft®, Puros®) blocks in a wet and dry state. While no significant differences could be seen in dry state, cerabone® and maxresorb® blocks showed a slight height decrease in wet state, whereas both maxgraft® and Puros® had an almost identical height increase. In addition, cerabone® and maxresorb® blocks remained highly rigid and their damping behaviour was not influenced by the water. On the other hand, both maxgraft® and Puros® had a strong increase in their molecular mobility with different damping behaviour profiles during the wet state. A high-speed microscopical imaging system was used to analyze the hydrophilicity in several naturally derived (cerabone®, Bio-Oss®, NuOss®, SIC® nature graft) and synthetic DBGS granules (maxresorb®, BoneCeramic®, NanoBone®, Ceros®). The highest level of hydrophilicity was detected in cerabone® and maxresorb®, while Bio-Oss® and BoneCeramic® had the lowest level of hydrophilicity among both naturally derived and synthetic DBGS groups. Deviations among the DBGS were also addressed via physicochemical differences recorded by Micro Computed Tomography, Scanning Electron Microscopy, Fourier Transform Infrared Spectroscopy, X-ray powder Diffractometry, and Thermogravimetric Analysis. Such DBGS variations could influence the volume stability at the grafting site, handling as well as the speed of vascularization and bone regeneration. Therefore, this study initiates a new insight into the DBGS differences and their importance for successful clinical results. Full article
(This article belongs to the Special Issue Bone Substitute Materials)
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Open AccessArticle 3D Powder Printed Bioglass and β-Tricalcium Phosphate Bone Scaffolds
Materials 2018, 11(1), 13; https://doi.org/10.3390/ma11010013
Received: 23 October 2017 / Revised: 18 December 2017 / Accepted: 18 December 2017 / Published: 22 December 2017
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Abstract
The use of both bioglass (BG) and β tricalcium phosphate (β-TCP) for bone replacement applications has been studied extensively due to the materials’ high biocompatibility and ability to resorb when implanted in the body. 3D printing has been explored as a fast and
[...] Read more.
The use of both bioglass (BG) and β tricalcium phosphate (β-TCP) for bone replacement applications has been studied extensively due to the materials’ high biocompatibility and ability to resorb when implanted in the body. 3D printing has been explored as a fast and versatile technique for the fabrication of porous bone scaffolds. This project investigates the effects of using different combinations of a composite BG and β-TCP powder for 3D printing of porous bone scaffolds. Porous 3D powder printed bone scaffolds of BG, β-TCP, 50/50 BG/β-TCP and 70/30 BG/β-TCP compositions were subject to a variety of characterization and biocompatibility tests. The porosity characteristics, surface roughness, mechanical strength, viability for cell proliferation, material cytotoxicity and in vitro bioactivity were assessed. The results show that the scaffolds can support osteoblast-like MG-63 cells growth both on the surface of and within the scaffold material and do not show alarming cytotoxicity; the porosity and surface characteristics of the scaffolds are appropriate. Of the two tested composite materials, the 70/30 BG/β-TCP scaffold proved to be superior in terms of biocompatibility and mechanical strength. The mechanical strength of the scaffolds makes them unsuitable for load bearing applications. However, they can be useful for other applications such as bone fillers. Full article
(This article belongs to the Special Issue Bone Substitute Materials)
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Open AccessArticle Impact of Surface Potential on Apatite Formation in Ti Alloys Subjected to Acid and Heat Treatments
Materials 2017, 10(10), 1127; https://doi.org/10.3390/ma10101127
Received: 29 August 2017 / Revised: 13 September 2017 / Accepted: 21 September 2017 / Published: 24 September 2017
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Abstract
Titanium metal (Ti) and its alloys are widely used in orthopedic and dental fields. We have previously shown that acid and heat treatment was effective to introduce bone bonding, osteoconduction and osteoinduction on pure Ti. In the present study, acid and heat treatment
[...] Read more.
Titanium metal (Ti) and its alloys are widely used in orthopedic and dental fields. We have previously shown that acid and heat treatment was effective to introduce bone bonding, osteoconduction and osteoinduction on pure Ti. In the present study, acid and heat treatment with or without initial NaOH treatment was performed on typical Ti-based alloys used in orthopedic and dental fields. Dynamic movements of alloying elements were developed, which depended on the kind of treatment and type of alloy. It was found that the simple acid and heat treatment enriched/remained the alloying elements on Ti–6Al–4V, Ti–15Mo–5Zr–3Al and Ti–15Zr–4Nb–4Ta, resulting in neutral surface charges. Thus, the treated alloys did not form apatite in a simulated body fluid (SBF) within 3 days. In contrast, when the alloys were subjected to a NaOH treatment prior to an acid and heat treatment, alloying elements were selectively removed from the alloy surfaces. As a result, the treated alloys became positively charged, and formed apatite in SBF within 3 days. Thus, the treated alloys would be useful in orthopedic and dental fields since they form apatite even in a living body and bond to bone. Full article
(This article belongs to the Special Issue Bone Substitute Materials)
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Review

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Open AccessReview The Components of Bone and What They Can Teach Us about Regeneration
Materials 2018, 11(1), 14; https://doi.org/10.3390/ma11010014
Received: 7 December 2017 / Revised: 20 December 2017 / Accepted: 21 December 2017 / Published: 22 December 2017
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Abstract
The problem of bone regeneration has engaged both physicians and scientists since the beginning of medicine. Not only can bone heal itself following most injuries, but when it does, the regenerated tissue is often indistinguishable from healthy bone. Problems arise, however, when bone
[...] Read more.
The problem of bone regeneration has engaged both physicians and scientists since the beginning of medicine. Not only can bone heal itself following most injuries, but when it does, the regenerated tissue is often indistinguishable from healthy bone. Problems arise, however, when bone does not heal properly, or when new tissue is needed, such as when two vertebrae are required to fuse to stabilize adjacent spine segments. Despite centuries of research, such procedures still require improved therapeutic methods to be devised. Autologous bone harvesting and grafting is currently still the accepted benchmark, despite drawbacks for clinicians and patients that include limited amounts, donor site morbidity, and variable quality. The necessity for an alternative to this “gold standard” has given rise to a bone-graft and substitute industry, with its central conundrum: what is the best way to regenerate bone? In this review, we dissect bone anatomy to summarize our current understanding of its constituents. We then look at how various components have been employed to improve bone regeneration. Evolving strategies for bone regeneration are then considered. Full article
(This article belongs to the Special Issue Bone Substitute Materials)
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