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Bone Substitute Materials

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

Deadline for manuscript submissions: closed (30 April 2018) | Viewed by 76843

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Prof. Dr. Steven J. Eppell

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Guest Editor

Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106, USA
Interests: orthopedic biomaterials; nanotechnology; atomic force microscopy; nanomechanics; collagen

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

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Keywords

Bone
biomaterial
collagen
mineral
ground substance
biomechanics
remodelling
biocompatible
osteoblast
osteoclast

Published Papers (12 papers)

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Research

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19 pages, 10004 KiB

Open AccessArticle

Cell Type Influences Local Delivery of Biomolecules from a Bioinspired Apatite Drug Delivery System

by Jumana Alhamdi, Emily Jacobs, Gloria Gronowicz, Nadia Benkirane-Jessel, Marja Hurley and Liisa Kuhn

Materials 2018, 11(9), 1703; https://doi.org/10.3390/ma11091703 - 13 Sep 2018

Cited by 6 | Viewed by 3475

Abstract

Recently, the benefit of step-wise sequential delivery of fibroblast growth factor-2 (FGF-2) and bone morphogenetic protein-2 from a bioinspired apatite drug delivery system on mouse calvarial bone repair was demonstrated. The thicknesses of the nanostructured poly-l-Lysine/poly-l-Glutamic acid polyelectrolyte multilayer (PEM) and the bone-like apatite barrier layer that make up the delivery system, were varied. The effects of the structural variations of the coating on the kinetics of cell access to a cytotoxic factor delivered by the layered structure were evaluated. FGF-2 was adsorbed into the outer PEM, and cytotoxic antimycin-A (AntiA) was adsorbed to the substrate below the barrier layer to detect the timing of the cell access. While MC3T3-E1 osteoprogenitor cells accessed AntiA after three days, the RAW 264.7 macrophage access occurred within 4 h, unless the PEM layer was removed, in which case the results were reversed. Pits were created in the coating by the RAW 264.7 macrophages and initiated delivery, while the osteoprogenitor cell access to drugs occurred through a solution-mediated coating dissolution, at junctions between the islands of crystals. Macrophage-mediated degradation is therefore a mechanism that controls drug release from coatings containing bioinspired apatite. Full article

(This article belongs to the Special Issue Bone Substitute Materials)

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19 pages, 5188 KiB

Open AccessArticle

Hierarchical Characterization and Nanomechanical Assessment of Biomimetic Scaffolds Mimicking Lamellar Bone via Atomic Force Microscopy Cantilever-Based Nanoindentation

by Brian Wingender, Yongliang Ni, Yifan Zhang, Curtis Taylor and Laurie Gower

Materials 2018, 11(7), 1257; https://doi.org/10.3390/ma11071257 - 22 Jul 2018

Cited by 8 | Viewed by 4579

Abstract

The hierarchical structure of bone and intrinsic material properties of its two primary constituents, carbonated apatite and fibrillar collagen, when being synergistically organized into an interpenetrating hard-soft composite, contribute to its excellent mechanical properties. Lamellar bone is the predominant structural motif in mammalian hard tissues; therefore, we believe the fabrication of a collagen/apatite composite with a hierarchical structure that emulates bone, consisting of a dense lamellar microstructure and a mineralized collagen fibril nanostructure, is an important first step toward the goal of regenerative bone tissue engineering. In this work, we exploit the liquid crystalline properties of collagen to fabricate dense matrices that assemble with cholesteric organization. The matrices were crosslinked via carbodiimide chemistry to improve mechanical properties, and are subsequently mineralized via the polymer-induced liquid-precursor (PILP) process to promote intrafibrillar mineralization. Neither the crosslinking procedure nor the mineralization affected the cholesteric collagen microstructures; notably, there was a positive trend toward higher stiffness with increasing crosslink density when measured by cantilever-based atomic force microscopy (AFM) nanoindentation. In the dry state, the average moduli of moderately (X51; 4.8 ± 4.3 GPa) and highly (X76; 7.8 ± 6.7 GPa) crosslinked PILP-mineralized liquid crystalline collagen (LCC) scaffolds were higher than the average modulus of bovine bone (5.5 ± 5.6 GPa). Full article

(This article belongs to the Special Issue Bone Substitute Materials)

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16 pages, 4770 KiB

Open AccessArticle

A Novel Multiscale Mathematical Model for Building Bone Substitute Materials for Children

by Abdennasser Chekroun, Laurent Pujo-Menjouet and Jean-Philippe Berteau

Materials 2018, 11(6), 1045; https://doi.org/10.3390/ma11061045 - 20 Jun 2018

Cited by 2 | Viewed by 3561

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 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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8 pages, 966 KiB

Open AccessArticle

Influence of Absorbable Calcium Sulfate-Based Bone Substitute Materials on Human Haemostasis—In Vitro Biological Behavior of Antibiotic Loaded Implants

by Dominik Pförringer, Norbert Harrasser, Marc Beirer, Moritz Crönlein, Axel Stemberger, Martijn Van Griensven, Martin Lucke, Rainer Burgkart and Andreas Obermeier

Materials 2018, 11(6), 935; https://doi.org/10.3390/ma11060935 - 01 Jun 2018

Cited by 8 | Viewed by 3506

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 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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9 pages, 3327 KiB

Open AccessArticle

Histological Evaluation of the Healing Process of Various Bone Graft Materials after Engraftment into the Human Body

by Sang Hyun Jo, Young-Kyun Kim and Yong-Hoon Choi

Materials 2018, 11(5), 714; https://doi.org/10.3390/ma11050714 - 02 May 2018

Cited by 18 | Viewed by 4624

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^®, 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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17 pages, 5905 KiB

Open AccessArticle

Synthesis, Characterization and In Vitro Study of Synthetic and Bovine-Derived Hydroxyapatite Ceramics: A Comparison

by July Andrea Rincón-López, Jennifer Andrea Hermann-Muñoz, Astrid Lorena Giraldo-Betancur, Andrea De Vizcaya-Ruiz, Juan Manuel Alvarado-Orozco and Juan Muñoz-Saldaña

Materials 2018, 11(3), 333; https://doi.org/10.3390/ma11030333 - 25 Feb 2018

Cited by 52 | Viewed by 6102

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 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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10 pages, 4875 KiB

Open AccessArticle

Efficacy of Octacalcium Phosphate Collagen Composite for Titanium Dental Implants in Dogs

by Tadashi Kawai, Keiko Matsui, Yushi Ezoe, Fumihiko Kajii, Osamu Suzuki, Tetsu Takahashi and Shinji Kamakura

Materials 2018, 11(2), 229; https://doi.org/10.3390/ma11020229 - 02 Feb 2018

Cited by 10 | Viewed by 4723

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. 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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19 pages, 35647 KiB

Open AccessArticle

Hydrophilicity, Viscoelastic, and Physicochemical Properties Variations in Dental Bone Grafting Substitutes

by Branko Trajkovski, Matthias Jaunich, Wolf-Dieter Müller, Florian Beuer, Gregory-George Zafiropoulos and Alireza Houshmand

Materials 2018, 11(2), 215; https://doi.org/10.3390/ma11020215 - 30 Jan 2018

Cited by 43 | Viewed by 8142

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 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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7622 KiB

Open AccessArticle

3D Powder Printed Bioglass and β-Tricalcium Phosphate Bone Scaffolds

by Michael Seidenstuecker, Laura Kerr, Anke Bernstein, Hermann O. Mayr, Norbert P. Suedkamp, Rainer Gadow, Peter Krieg, Sergio Hernandez Latorre, Ralf Thomann, Frank Syrowatka and Steffen Esslinger

Materials 2018, 11(1), 13; https://doi.org/10.3390/ma11010013 - 22 Dec 2017

Cited by 72 | Viewed by 7781

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 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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2960 KiB

Open AccessArticle

Impact of Surface Potential on Apatite Formation in Ti Alloys Subjected to Acid and Heat Treatments

by Seiji Yamaguchi, Hideki Hashimoto, Ryusuke Nakai and Hiroaki Takadama

Materials 2017, 10(10), 1127; https://doi.org/10.3390/ma10101127 - 24 Sep 2017

Cited by 7 | Viewed by 4958

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 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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16 pages, 6360 KiB

Open AccessReview

Minor Review: An Overview of a Synthetic Nanophase Bone Substitute

by Steven J. Eppell, Weidong Tong, James McMasters, Yohannes Soenjaya, Anca M. Barbu, Alvin Ko and Jonathan Z. Baskin

Materials 2018, 11(9), 1556; https://doi.org/10.3390/ma11091556 - 29 Aug 2018

Cited by 4 | Viewed by 3315

Abstract

Material is reviewed that consists of reconstituted collagen fibril gel mineralized in a manner that produces biomimetically sized nanoapatites intimately associated with the fibrils. This gel is formed into usable shapes with a modulus and strength that allow it to be surgically press fitted into bony defects. The design paradigm for the material is that the nanoapatites will dissolve into soluble Ca²⁺ as the collagen is degraded into RGD-containing peptide fragments due to osteoclastic action. This is intended to signal to the osteoclasts to continue removing the material in a biomimetic fashion similar to bony remodeling. Preliminary experiments in a subcutaneous rat model show that the material is biocompatible with respect to inflammatory and immunogenic responses, and that it supports cellular invasion. Preliminary experiments in a critical-sized mandibular defect in rats show that the material is resorbable and functions well as a bone morphogenetic 2 (BMP-2) carrier. We have produced a range of mechanical and biological responses by varying mechanical and chemical processing of the material. Full article

(This article belongs to the Special Issue Bone Substitute Materials)

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1575 KiB

Open AccessReview

The Components of Bone and What They Can Teach Us about Regeneration

by Bach Quang Le, Victor Nurcombe, Simon McKenzie Cool, Clemens A. Van Blitterswijk, Jan De Boer and Vanessa Lydia Simone LaPointe

Materials 2018, 11(1), 14; https://doi.org/10.3390/ma11010014 - 22 Dec 2017

Cited by 56 | Viewed by 21059

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 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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