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Biomaterials for Bone Tissue Engineering 4.0
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Biomaterials for Bone Tissue Engineering 4.0

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 (15 March 2024) | Viewed by 6805

Special Issue Editors

Dr. Mike Barbeck

E-Mail Website
Guest Editor
Clinic and Policlinic for Dermatology and Venereology, University Medical Center Rostock, 18057 Rostock, Germany
Interests: bone substitutes; collagen-based biomaterials for soft and hard tissue regeneration; foreign body response to biomaterials; inflammation; macrophages, multinucleated giant cells, degradation processes of biomaterials; phagocytosis; vascularization; histology; immunohistochemistry; histomorphometry
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Reinhard Schnettler

E-Mail Website
Guest Editor
University Medical Centre, Justus Liebig University of Giessen, 35390 Giessen, Germany
Interests: bone
Dr. Ole Jung

E-Mail Website
Guest Editor
Clinic and Policlinic for Dermatology and Venereology, University Medical Center Rostock, 18057 Rostock, Germany
Interests: magnesium; surfaces; coating technologies; biomaterials
Special Issues, Collections and Topics in MDPI journals

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 and tissue engineering concepts.

This Special Issue focuses on the various aspects of interactions of bone substitutes with cells and tissues. Thus, we invite contributions of reviews and 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.

Dr. Mike Barbeck
Prof. Dr. Reinhard Schnettler
Dr. Ole Jung
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. 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 tissue regeneration
  • bone substitute
  • bone tissue engineering
  • tissue reactions
  • biomaterial

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Published Papers (5 papers)

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Research

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15 pages, 4535 KiB  
Article
Collagen-like Osteoclast-Associated Receptor (OSCAR)-Binding Motifs Show a Co-Stimulatory Effect on Osteoclastogenesis in a Peptide Hydrogel System
by Mattia Vitale, Cosimo Ligorio, Stephen M. Richardson, Judith A. Hoyland and Jordi Bella
Int. J. Mol. Sci. 2024, 25(1), 445; https://doi.org/10.3390/ijms25010445 - 28 Dec 2023
Viewed by 782
Abstract
Osteoclastogenesis, one of the dynamic pathways underlying bone remodelling, is a complex process that includes many stages. This complexity, while offering a wealth of therapeutic opportunities, represents a substantial challenge in unravelling the underlying mechanisms. As such, there is a high demand for [...] Read more.
Osteoclastogenesis, one of the dynamic pathways underlying bone remodelling, is a complex process that includes many stages. This complexity, while offering a wealth of therapeutic opportunities, represents a substantial challenge in unravelling the underlying mechanisms. As such, there is a high demand for robust model systems to understand osteoclastogenesis. Hydrogels seeded with osteoclast precursors and decorated with peptides or proteins mimicking bone’s extracellular matrix could provide a useful synthetic tool to study pre-osteoclast-matrix interactions and their effect on osteoclastogenesis. For instance, fibrillar collagens have been shown to provide a co-stimulatory pathway for osteoclastogenesis through interaction with the osteoclast-associated receptor (OSCAR), a regulator of osteoclastogenesis expressed on the surface of pre-osteoclast cells. Based on this rationale, here we design two OSCAR-binding peptides and one recombinant OSCAR-binding protein, and we combine them with peptide-based hydrogels to study their effect on osteoclastogenesis. The OSCAR-binding peptides adopt the collagen triple-helical conformation and interact with OSCAR, as shown by circular dichroism spectropolarimetry and surface plasmon resonance. Furthermore, they have a positive effect on osteoclastogenesis, as demonstrated by appropriate gene expression and tartrate-resistant acid phosphatase staining typical of osteoclast formation. Combination of the OSCAR-binding peptides or the OSCAR-binding recombinant protein with peptide-based hydrogels enhances osteoclast differentiation when compared to the non-modified hydrogels, as demonstrated by multi-nucleation and by F-actin staining showing a characteristic osteoclast-like morphology. We envisage that these hydrogels could be used as a platform to study osteoclastogenesis and, in particular, to investigate the effect of costimulatory pathways involving OSCAR. Full article
(This article belongs to the Special Issue Biomaterials for Bone Tissue Engineering 4.0)
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15 pages, 6108 KiB  
Article
Novel Double Hybrid-Type Bone Cements Based on Calcium Phosphates, Chitosan and Citrus Pectin
by Piotr Pańtak, Joanna P. Czechowska, Ewelina Cichoń and Aneta Zima
Int. J. Mol. Sci. 2023, 24(17), 13455; https://doi.org/10.3390/ijms241713455 - 30 Aug 2023
Cited by 2 | Viewed by 681
Abstract
In this work, the influence of the liquid phase composition on the physicochemical properties of double hybrid-type bone substitutes was investigated. The solid phase of obtained biomicroconcretes was composed of highly reactive α-tricalcium phosphate powder (α-TCP) and hybrid hydroxyapatite/chitosan granules (HA/CTS). Various combinations [...] Read more.
In this work, the influence of the liquid phase composition on the physicochemical properties of double hybrid-type bone substitutes was investigated. The solid phase of obtained biomicroconcretes was composed of highly reactive α-tricalcium phosphate powder (α-TCP) and hybrid hydroxyapatite/chitosan granules (HA/CTS). Various combinations of disodium phosphate (Na2HPO4) solution and citrus pectin gel were used as liquid phases. The novelty of this study is the development of double-hybrid materials with a dual setting system. The double hybrid phenomenon is due to the interactions between polycationic polymer (chitosan in hybrid granules) and polyanionic polymer (citrus pectin). The chemical and phase composition (FTIR, XRD), setting times (Gillmore needles), injectability, mechanical strength, microstructure (SEM) and chemical stability in vitro were studied. The setting times of obtained materials ranged from 4.5 to 30.5 min for initial and from 7.5 to 55.5 min for final setting times. The compressive strength varied from 5.75 to 13.24 MPa. By incorporating citrus pectin into the liquid phase of the materials, not only did it enhance their physicochemical properties, but it also resulted in the development of fully injectable materials featuring a dual setting system. It has been shown that the properties of materials can be controlled by using the appropriate ratio of citrus pectin in the liquid phase. Full article
(This article belongs to the Special Issue Biomaterials for Bone Tissue Engineering 4.0)
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12 pages, 5561 KiB  
Article
Polylevolysine and Fibronectin-Loaded Nano-Hydroxyapatite/PGLA/Dextran-Based Scaffolds for Improving Bone Regeneration: A Histomorphometric in Animal Study
by Elena Canciani, Paola Straticò, Vincenzo Varasano, Claudia Dellavia, Chiara Sciarrini, Lucio Petrizzi, Lia Rimondini and Elena M. Varoni
Int. J. Mol. Sci. 2023, 24(9), 8137; https://doi.org/10.3390/ijms24098137 - 02 May 2023
Cited by 2 | Viewed by 1217
Abstract
The regeneration of large bone defects is still demanding, requiring biocompatible scaffolds, with osteoconductive and osteoinductive properties. This study aimed to assess the pre-clinical efficacy of a nano-hydroxyapatite (nano-HA)/PGLA/dextran-based scaffold loaded with Polylevolysine (PLL) and fibronectin (FN), intended for bone regeneration of a [...] Read more.
The regeneration of large bone defects is still demanding, requiring biocompatible scaffolds, with osteoconductive and osteoinductive properties. This study aimed to assess the pre-clinical efficacy of a nano-hydroxyapatite (nano-HA)/PGLA/dextran-based scaffold loaded with Polylevolysine (PLL) and fibronectin (FN), intended for bone regeneration of a critical-size tibial defect, using an ovine model. After physicochemical characterization, the scaffolds were implanted in vivo, producing two monocortical defects on both tibiae of ten adult sheep, randomly divided into two groups to be euthanized at three and six months after surgery. The proximal left and right defects were filled, respectively, with the test scaffold (nano-HA/PGLA/dextran-based scaffold loaded with PLL and FN) and the control scaffold (nano-HA/PGLA/dextran-based scaffold not loaded with PLL and FN); the distal defects were considered negative control sites, not receiving any scaffold. Histological and histomorphometric analyses were performed to quantify the bone ingrowth and residual material 3 and 6 months after surgery. In both scaffolds, the morphological analyses, at the SEM, revealed the presence of submicrometric crystals on the surfaces and within the scaffolds, while optical microscopy showed a macroscopic 3D porous architecture. XRD confirmed the presence of nano-HA with a high level of crystallinity degree. At the histological and histomorphometric evaluation, new bone formation and residual biomaterial were detectable inside the defects 3 months after intervention, without differences between the scaffolds. At 6 months, the regenerated bone was significantly higher in the defects filled with the test scaffold (loaded with PLL and FN) than in those filled with the control scaffold, while the residual material was higher in correspondence to the control scaffold. Nano-HA/PGLA/dextran-based scaffolds loaded with PLL and FN appear promising in promoting bone regeneration in critical-size defects, showing balanced regenerative and resorbable properties to support new bone deposition. Full article
(This article belongs to the Special Issue Biomaterials for Bone Tissue Engineering 4.0)
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21 pages, 5082 KiB  
Article
Analyses of the Cellular Interactions between the Ossification of Collagen-Based Barrier Membranes and the Underlying Bone Defects
by Said Alkildani, Yanru Ren, Luo Liu, Denis Rimashevskiy, Reinhard Schnettler, Milena Radenković, Stevo Najman, Sanja Stojanović, Ole Jung and Mike Barbeck
Int. J. Mol. Sci. 2023, 24(7), 6833; https://doi.org/10.3390/ijms24076833 - 06 Apr 2023
Cited by 2 | Viewed by 1618
Abstract
Barrier membranes are an essential tool in guided bone Regeneration (GBR), which have been widely presumed to have a bioactive effect that is beyond their occluding and space maintenance functionalities. A standardized calvaria implantation model was applied for 2, 8, and 16 weeks [...] Read more.
Barrier membranes are an essential tool in guided bone Regeneration (GBR), which have been widely presumed to have a bioactive effect that is beyond their occluding and space maintenance functionalities. A standardized calvaria implantation model was applied for 2, 8, and 16 weeks on Wistar rats to test the interactions between the barrier membrane and the underlying bone defects which were filled with bovine bone substitute materials (BSM). In an effort to understand the barrier membrane’s bioactivity, deeper histochemical analyses, as well as the immunohistochemical detection of macrophage subtypes (M1/M2) and vascular endothelial cells, were conducted and combined with histomorphometric and statistical approaches. The native collagen-based membrane was found to have ossified due to its potentially osteoconductive and osteogenic properties, forming a “bony shield” overlying the bone defects. Histomorphometrical evaluation revealed the resorption of the membranes and their substitution with bone matrix. The numbers of both M1- and M2-macrophages were significantly higher within the membrane compartments compared to the underlying bone defects. Thereby, M2-macrophages significantly dominated the tissue reaction within the membrane compartments. Statistically, a correlation between M2-macropahges and bone regeneration was only found at 2 weeks post implantationem, while the pro-inflammatory limb of the immune response correlated with the two processes at 8 weeks. Altogether, this study elaborates on the increasingly described correlations between barrier membranes and the underlying bone regeneration, which sheds a light on the understanding of the immunomodulatory features of biomaterials. Full article
(This article belongs to the Special Issue Biomaterials for Bone Tissue Engineering 4.0)
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Review

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27 pages, 5189 KiB  
Review
The Role of HIF-1α in Bone Regeneration: A New Direction and Challenge in Bone Tissue Engineering
by Jiaqian You, Manxuan Liu, Minghui Li, Shaobo Zhai, Sezhen Quni, Lu Zhang, Xiuyu Liu, Kewen Jia, Yidi Zhang and Yanmin Zhou
Int. J. Mol. Sci. 2023, 24(9), 8029; https://doi.org/10.3390/ijms24098029 - 28 Apr 2023
Cited by 2 | Viewed by 1863
Abstract
The process of repairing significant bone defects requires the recruitment of a considerable number of cells for osteogenesis-related activities, which implies the consumption of a substantial amount of oxygen and nutrients. Therefore, the limited supply of nutrients and oxygen at the defect site [...] Read more.
The process of repairing significant bone defects requires the recruitment of a considerable number of cells for osteogenesis-related activities, which implies the consumption of a substantial amount of oxygen and nutrients. Therefore, the limited supply of nutrients and oxygen at the defect site is a vital constraint that affects the regenerative effect, which is closely related to the degree of a well-established vascular network. Hypoxia-inducible factor (HIF-1α), which is an essential transcription factor activated in hypoxic environments, plays a vital role in vascular network construction. HIF-1α, which plays a central role in regulating cartilage and bone formation, induces vascular invasion and differentiation of osteoprogenitor cells to promote and maintain extracellular matrix production by mediating the adaptive response of cells to changes in oxygen levels. However, the application of HIF-1α in bone tissue engineering is still controversial. As such, clarifying the function of HIF-1α in regulating the bone regeneration process is one of the urgent issues that need to be addressed. This review provides insight into the mechanisms of HIF-1α action in bone regeneration and related recent advances. It also describes current strategies for applying hypoxia induction and hypoxia mimicry in bone tissue engineering, providing theoretical support for the use of HIF-1α in establishing a novel and feasible bone repair strategy in clinical settings. Full article
(This article belongs to the Special Issue Biomaterials for Bone Tissue Engineering 4.0)
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