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Bone Substitute Material
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Bone Substitute Material

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Macromolecules".

Deadline for manuscript submissions: closed (31 March 2021) | Viewed by 19962

Special Issue Editor

Prof. Dr. Marcus Jäger

E-Mail Website
Guest Editor
Department of Orthopedics, Trauma and Reconstructive Surgery, St. Marien Hospital Mülheim an der Ruhr, D-45468 Mülheim/Ruhr, Germany
Interests: innovative materials (bone substitute materials, biometals, ceramics, auto- and allografts); bone and cartilage regeneration and the diagnosis and therapy of osteonecrosis

Special Issue Information

Dear Colleagues,

Critical size bone defects still remain challenging in orthopedic and trauma surgery. Typical examples are bone loss caused by limb-preserving musculoskeletal tumor operations, trauma-associated bone destruction or bone loss due to implant-related complication such as periprosthetic loosening or infection. Moreover, the demographics in many countries of the Western world have shown an increase in the populations of elderly people, which demands special treatment concepts for the osteoporotic bone. Here, bone substitute materials are promising candidates to bridge bone defects. They can act as scaffold for the local tissue, allowing bone regeneration (osteoconduction), may promote local bone formation (osteopromotion) or induct bone regeneration (osteoinduction). Here, both cell–material interactions and material properties determine the further healing. Therefore, strong efforts have been made to design and compose innovative bone substitute materials qualified for bone regeneration. Surface modifications, nanotechnology, and in silico models present innovative inputs. There is evidence that interdisciplinary approaches including combination with biologicals such as cytokines, growth factors or cell-therapeutics will revolutionize the application of existing bone substitute materials. However, due to legal restrictions, the clinical application of these materials is restricted. This edition presents the latest research results and future perspectives in bone substitute material research.

Prof. Dr. Marcus Jäger
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 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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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 substitutes
  • biomaterials
  • bone defects
  • regeneration
  • ceramics
  • scaffolds

Published Papers (6 papers)

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Research

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19 pages, 2810 KiB  
Article
Benefits and Biosafety of Use of 3D-Printing Technology for Titanium Biomedical Implants: A Pilot Study in the Rabbit Model
by Sabrina Livia Ng, Subhabrata Das, Yen-Peng Ting, Raymond Chung Wen Wong and Nattharee Chanchareonsook
Int. J. Mol. Sci. 2021, 22(16), 8480; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22168480 - 06 Aug 2021
Cited by 11 | Viewed by 2395
Abstract
Background: Titanium has been used in osteosynthesis for decades and its compatibility and safety is unquestioned. Studies have shown that there is release and collection of titanium in the organ systems with little note of toxicity. The gold standard is considered to be [...] Read more.
Background: Titanium has been used in osteosynthesis for decades and its compatibility and safety is unquestioned. Studies have shown that there is release and collection of titanium in the organ systems with little note of toxicity. The gold standard is considered to be titanium osteosynthesis plate produced by milling methods. The use of customized titanium plates produced with 3D printing, specifically direct metal laser sintering, have found increasing use in recent years. It is unknown how much titanium is released in these printed titanium implants, which is known to be potentially porous, depending on the heat settings of the printer. We hypothesize that the amount of titanium released in printed titanium implants may be potentially more or equal compared to the gold standard, which is the implant produced by milling. Methods: We studied the biosafety of this technology and its products by measuring serum and organ titanium levels after implantation of 3D-printed versus traditionally fabrication titanium plates and screws in a pilot study using the rabbit model. A total of nine rabbits were used, with three each in the control, milled and printed titanium group. The animals were euthanized after six months. Serum and organs of the reticuloendothelial system were harvested, digested and assayed for titanium levels. Results: Organ and serum titanium levels were significantly higher in rabbit subjects implanted with titanium implants (milled and printed) compared to the control group. However, there was no significant difference in organ and serum titanium levels of subjects implanted with milled and traditionally fabricated titanium implants. Conclusions: The biosafety of use of 3D-printed titanium implants and traditionally fabricated titanium implants are comparable. With this in mind, 3D-printed custom implants can not only replace, but will very possibly surpass traditionally fabricated titanium implants in the mode and extent of use. Full article
(This article belongs to the Special Issue Bone Substitute Material)
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18 pages, 3017 KiB  
Article
Chemotactic and Angiogenic Potential of Mineralized Collagen Scaffolds Functionalized with Naturally Occurring Bioactive Factor Mixtures to Stimulate Bone Regeneration
by Henriette Bretschneider, Mandy Quade, Anja Lode, Michael Gelinsky, Stefan Rammelt and Corina Vater
Int. J. Mol. Sci. 2021, 22(11), 5836; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22115836 - 29 May 2021
Cited by 9 | Viewed by 2561
Abstract
To develop cost-effective and efficient bone substitutes for improved regeneration of bone defects, heparin-modified mineralized collagen scaffolds were functionalized with concentrated, naturally occurring bioactive factor mixtures derived from adipose tissue, platelet-rich plasma and conditioned medium from a hypoxia-treated human bone marrow-derived mesenchymal stem [...] Read more.
To develop cost-effective and efficient bone substitutes for improved regeneration of bone defects, heparin-modified mineralized collagen scaffolds were functionalized with concentrated, naturally occurring bioactive factor mixtures derived from adipose tissue, platelet-rich plasma and conditioned medium from a hypoxia-treated human bone marrow-derived mesenchymal stem cell line. Besides the analysis of the release kinetics of functionalized scaffolds, the bioactivity of the released bioactive factors was tested with regard to chemotaxis and angiogenic tube formation. Additionally, functionalized scaffolds were seeded with human bone marrow-derived mesenchymal stromal cells (hBM-MSC) and their osteogenic and angiogenic potential was investigated. The release of bioactive factors from the scaffolds was highest within the first 3 days. Bioactivity of the released factors could be confirmed for all bioactive factor mixtures by successful chemoattraction of hBM-MSC in a transwell assay as well as by the formation of prevascular structures in a 2D co-culture system of hBM-MSC and human umbilical vein endothelial cells. The cells seeded directly onto the functionalized scaffolds were able to express osteogenic markers and form tubular networks. In conclusion, heparin-modified mineralized collagen scaffolds could be successfully functionalized with naturally occurring bioactive factor mixtures promoting cell migration and vascularization. Full article
(This article belongs to the Special Issue Bone Substitute Material)
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18 pages, 13888 KiB  
Article
Synthesis, Characterization, Antibacterial Properties, and In Vitro Studies of Selenium and Strontium Co-Substituted Hydroxyapatite
by Muhammad Maqbool, Qaisar Nawaz, Muhammad Atiq Ur Rehman, Mark Cresswell, Phil Jackson, Katrin Hurle, Rainer Detsch, Wolfgang H. Goldmann, Asma Tufail Shah and Aldo R. Boccaccini
Int. J. Mol. Sci. 2021, 22(8), 4246; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22084246 - 19 Apr 2021
Cited by 18 | Viewed by 3599
Abstract
In this study, as a measure to enhance the antimicrobial activity of biomaterials, the selenium ions have been substituted into hydroxyapatite (HA) at different concentration levels. To balance the potential cytotoxic effects of selenite ions (SeO32−) in HA, strontium (Sr [...] Read more.
In this study, as a measure to enhance the antimicrobial activity of biomaterials, the selenium ions have been substituted into hydroxyapatite (HA) at different concentration levels. To balance the potential cytotoxic effects of selenite ions (SeO32−) in HA, strontium (Sr2+) was co-substituted at the same concentration. Selenium and strontium-substituted hydroxyapatites (Se-Sr-HA) at equal molar ratios of x Se/(Se + P) and x Sr/(Sr + Ca) at (x = 0, 0.01, 0.03, 0.05, 0.1, and 0.2) were synthesized via the wet precipitation route and sintered at 900 °C. The effect of the two-ion concentration on morphology, surface charge, composition, antibacterial ability, and cell viability were studied. X-ray diffraction verified the phase purity and confirmed the substitution of selenium and strontium ions. Acellular in vitro bioactivity tests revealed that Se-Sr-HA was highly bioactive compared to pure HA. Se-Sr-HA samples showed excellent antibacterial activity against both Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus carnosus) bacterial strains. In vitro cell–material interaction, using human osteosarcoma cells MG-63 studied by WST-8 assay, showed that Se-HA has a cytotoxic effect; however, the co-substitution of strontium in Se-HA offsets the negative impact of selenium and enhanced the biological properties of HA. Hence, the prepared samples are a suitable choice for antibacterial coatings and bone filler applications. Full article
(This article belongs to the Special Issue Bone Substitute Material)
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Review

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17 pages, 1405 KiB  
Review
Role of Matrix-Associated Autologous Chondrocyte Implantation with Spheroids in the Treatment of Large Chondral Defects in the Knee: A Systematic Review
by Lucienne Angela Vonk, Giulietta Roël, Jacques Hernigou, Christian Kaps and Philippe Hernigou
Int. J. Mol. Sci. 2021, 22(13), 7149; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22137149 - 01 Jul 2021
Cited by 25 | Viewed by 4629
Abstract
Autologous chondrocyte implantation (ACI) is a cell therapy for the treatment of focal cartilage defects. The ACI product that is currently approved for use in the European Union (EU) consists of spheroids of autologous matrix-associated chondrocytes. These spheroids are spherical aggregates of ex [...] Read more.
Autologous chondrocyte implantation (ACI) is a cell therapy for the treatment of focal cartilage defects. The ACI product that is currently approved for use in the European Union (EU) consists of spheroids of autologous matrix-associated chondrocytes. These spheroids are spherical aggregates of ex vivo expanded human autologous chondrocytes and their self-synthesized extracellular matrix. The aim is to provide an overview of the preclinical and nonclinical studies that have been performed to ensure reproducible quality, safety, and efficacy of the cell therapy, and to evaluate the clinical data on ACI with spheroids. A systematic review was performed to include all English publications on self-aggregated spheroids of chondrocytes cultured in autologous serum without other supplements. A total of 20 publications were included, 7 pre- and nonclinical and 13 clinical research publications. The pre- and nonclinical research publications describe the development from concept to in vivo efficacy and quality- and safety-related aspects such as biodistribution, tumorigenicity, genetic stability, and potency. The evaluation of clinical research shows short- to mid-term safety and efficacy for the ACI with spheroid-based treatment of cartilage defects in both randomized clinical trials with selected patients, as well as in routine treatment providing real-world data in more complex patients. Full article
(This article belongs to the Special Issue Bone Substitute Material)
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12 pages, 1044 KiB  
Review
Functionalization of Synthetic Bone Substitutes
by André Busch, Marcus Jäger, Constantin Mayer and Andrea Sowislok
Int. J. Mol. Sci. 2021, 22(9), 4412; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22094412 - 23 Apr 2021
Cited by 14 | Viewed by 2486
Abstract
Bone substitutes have been applied to treat osseous defects for a long time. To prevent implant related infection (IRI) and enhance bone healing functionalized biomaterials, antibiotics and osteoinductive substances have been introduced. This study gives an overview of the current available surface-coated bone [...] Read more.
Bone substitutes have been applied to treat osseous defects for a long time. To prevent implant related infection (IRI) and enhance bone healing functionalized biomaterials, antibiotics and osteoinductive substances have been introduced. This study gives an overview of the current available surface-coated bone substitutes and provides an outlook for future perspectives. Full article
(This article belongs to the Special Issue Bone Substitute Material)
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15 pages, 1201 KiB  
Review
Role of Scaffolds, Subchondral, Intra-Articular Injections of Fresh Autologous Bone Marrow Concentrate Regenerative Cells in Treating Human Knee Cartilage Lesions: Different Approaches and Different Results
by Jacques Hernigou, Pascale Vertongen, Joanne Rasschaert and Philippe Hernigou
Int. J. Mol. Sci. 2021, 22(8), 3844; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22083844 - 08 Apr 2021
Cited by 13 | Viewed by 3157
Abstract
The value of bone marrow aspirate concentrates for treatment of human knee cartilage lesions is unclear. Most of the studies were performed with intra-articular injections. However, subchondral bone plays an important role in the progression of osteoarthritis. We investigated by a literature review [...] Read more.
The value of bone marrow aspirate concentrates for treatment of human knee cartilage lesions is unclear. Most of the studies were performed with intra-articular injections. However, subchondral bone plays an important role in the progression of osteoarthritis. We investigated by a literature review whether joint, subchondral bone, or/and scaffolds implantation of fresh autologous bone marrow aspirate concentrated (BMAC) containing mesenchymal stem cells (MSCs) would improve osteoarthritis (OA). There is in vivo evidence that suggests that all these different approaches (intra-articular injections, subchondral implantation, scaffolds loaded with BMAC) can improve the patient. This review analyzes the evidence for each different approach to treat OA. We found that the use of intra-articular injections resulted in a significant relief of pain symptoms in the short term and was maintained in 12 months. However, the clinical trials indicate that the application of autologous bone marrow concentrates in combination with scaffolds or in injection in the subchondral bone was superior to intra-articular injection for long-term results. The tendency of MSCs to differentiate into fibrocartilage affecting the outcome was a common issue faced by all the studies when biopsies were performed, except for scaffolds implantation in which some hyaline cartilage was found. The review suggests also that both implantation of subchondral BMAC and scaffolds loaded with BMAC could reduce the need for further surgery. Full article
(This article belongs to the Special Issue Bone Substitute Material)
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