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Biomaterials for Bone Repair and Regeneration

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A special issue of Bioengineering (ISSN 2306-5354). This special issue belongs to the section "Regenerative Engineering".

Deadline for manuscript submissions: 31 October 2024 | Viewed by 22267

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Special Issue Editor

Prof. Dr. Jianhua Li

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Guest Editor

Department of Biomaterials, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University, Jinan 250012, China
Interests: biomaterials; tissue engineering; nanomedicine; stem cells

Special Issue Information

Dear Colleagues,

The treatment of bone defects caused by trauma and disease is a common yet often challenging clinic issue. Biomaterials are an essential scaffolding substance for bone repair that can be engineered to deliver biofactors, stimulate cell functions, and construct a favorable microenvironment in order to support the bone tissue regeneration process. Numerous metals, ceramics, polymers, as well as their composites, have been processed to provide bone scaffolds, and some of them have already been used for practical applications, yet it is still challenging to design biomaterials that can achieve reliable bone repair and realize biomimetic bone regeneration. Therefore, engineering biomaterials that can actively engage with biological processes during bone repair and regeneration are highly desired.

The aim of this Special Issue is to demonstrate the recent development of novel biomaterials with engineered properties for bone repair and regeneration applications. This Special Issue is open to both original papers and reviews. The topics of interest include but are not limited to:

Advanced scaffold material design, preparation and modification techniques;
Novel bioactive material interface to regulate cellular behavior in bone regeneration process;
Material-mediated osteogenetic differentiation of stem cells/bone immunoregulation;
Bone-repairing materials with antibacterial properties;
Engineered biomaterials as drug/growth factor/gene/cell delivery systems for bone repair;
Reviews on recent development of biomaterials for bone tissue engineering;
Preclinical or clinical studies of materials for bone defect treatment.

Prof. Dr. Jianhua Li
Guest Editor

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Keywords

biomaterials
bone scaffold
bone tissue engineering
osteogenesis
regenerative medicine
bone immunoregulation
antibacterial bone scaffold
bone implant
bone defect treatment

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Published Papers (9 papers)

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Research

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12 pages, 1521 KiB

Open AccessArticle

Micro-Computed Tomography Analysis of Peri-Implant Bone Defects Exposed to a Peri-Implantitis Microcosm, with and without Bone Substitute, in a Rabbit Model: A Pilot Study

by Camila Panes, Iván Valdivia-Gandur, Carlos Veuthey, Vanessa Sousa, Mariano del Sol and Víctor Beltrán

Bioengineering 2024, 11(4), 397; https://doi.org/10.3390/bioengineering11040397 - 19 Apr 2024

Viewed by 1237

Abstract

Peri-implantitis is an inflammatory condition characterized by inflammation in the peri-implant connective tissue and a progressive loss of supporting bone; it is commonly associated with the presence of biofilms on the surface of the implant, which is an important factor in the development and progression of the disease. The objective of this study was to evaluate, using micro-CT, the bone regeneration of surgically created peri-implant defects exposed to a microcosm of peri-implantitis. Twenty-three adult New Zealand white rabbits were included in the study. Bone defects of 7 mm diameter were created in both tibiae, and a cap-shaped titanium device was placed in the center, counter-implanted with a peri-implantitis microcosm. The bone defects received a bone substitute and/or a resorbable synthetic PLGA membrane, according to random distribution. Euthanasia was performed 15 and 30 days postoperatively. Micro-CT was performed on all samples to quantify bone regeneration parameters. Bone regeneration of critical defects occurred in all experimental groups, with a significantly greater increase in cases that received bone graft treatment (p < 0.0001), in all measured parameters, at 15 and 30 days. No significant differences were observed in the different bone neoformation parameters between the groups that did not receive bone grafts (p > 0.05). In this experimental model, the presence of peri-implantitis microcosms was not a determining factor in the bone volume parameter, both in the groups that received regenerative treatment and in those that did not. Full article

(This article belongs to the Special Issue Biomaterials for Bone Repair and Regeneration)

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14 pages, 4448 KiB

Open AccessArticle

The Impact of Defect Size on Bone Healing in Critical-Size Bone Defects Investigated on a Rat Femur Defect Model Comparing Two Treatment Methods

by Andreas Kammerer, Frederik Alexander Hartmann, Christoph Nau, Maximilian Leiblein, Alexander Schaible, Jonas Neijhoft, Dirk Henrich, René Verboket and Maren Janko

Bioengineering 2024, 11(3), 287; https://doi.org/10.3390/bioengineering11030287 - 19 Mar 2024

Cited by 1 | Viewed by 1695

Abstract

Critical-size bone defects up to 25 cm can be treated successfully using the induced membrane technique established by Masquelet. To shorten this procedure, human acellular dermis (HAD) has had success in replacing this membrane in rat models. The aim of this study was to compare bone healing for smaller and larger defects using an induced membrane and HAD in a rat model. Using our established femoral defect model in rats, the animals were placed into four groups and defects of 5 mm or 10 mm size were set, either filling them with autologous spongiosa and surrounding the defect with HAD or waiting for the induced membrane to form around a cement spacer and filling this cavity in a second operation with a cancellous bone graft. Healing was assessed eight weeks after the operation using µ-CT, histological staining, and an assessment of the progress of bone formation using an established bone healing score. The α-smooth muscle actin used as a signal of blood vessel formation was stained and counted. The 5 mm defects showed significantly better bone union and a higher bone healing score than the 10 mm defects. HAD being used for the smaller defects resulted in a significantly higher bone healing score even than for the induced membrane and significantly higher blood vessel formation, corroborating the good results achieved by using HAD in previous studies. In comparison, same-sized groups showed significant differences in bone healing as well as blood vessel formation, suggesting that 5 mm defects are large enough to show different results in healing depending on treatment; therefore, 5 mm is a viable size for further studies on bone healing. Full article

(This article belongs to the Special Issue Biomaterials for Bone Repair and Regeneration)

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14 pages, 5812 KiB

Open AccessArticle

The Paracrine Effect of Hyaluronic Acid-Treated Endothelial Cells Promotes BMP-2-Mediated Osteogenesis

by Xiaojie Tong, Jin Chen, Renqin Wang, Dan Hou, Gang Wu, Chang Liu and Janak Lal Pathak

Bioengineering 2023, 10(10), 1227; https://doi.org/10.3390/bioengineering10101227 - 20 Oct 2023

Cited by 1 | Viewed by 1479

Abstract

The combination of hyaluronic acid (HA) and BMP-2 has been reported to promote bone regeneration. However, the interaction of endothelial cells and bone marrow mesenchymal stem cells (BMSCs) during HA + BMP-2 treatment is not fully understood. This study aimed to analyze the direct effect of HA, as well as the paracrine effect of HA-treated endothelial cells, on the BMP-2-mediated osteogenic differentiation of BMSCs. The angiogenic differentiation potential of HA at different molecular weights and different concentrations was tested. The direct effect of HA, as well as the indirect effect of HA-treated human umbilical cord endothelial cells (HUVECs, i.e., conditioned medium (CM)-based co-culture) on the BMP-2-mediated osteogenic differentiation of BMSCs was analyzed using alkaline phosphatase (ALP) staining and activity, alizarin red S (ARS) staining, and RT-qPCR of osteogenic markers. Angiogenic differentiation markers were also analyzed in HUVECs after treatment with HA + BMP-2. The bone regeneration potential of BMP-2 and HA + BMP-2 was analyzed in a rat ectopic model. We found that 1600 kDa HA at 300 µg/mL promoted tube formation by HUVECs in vitro and upregulated the mRNA expression of the angiogenic markers CD31, VEGF, and bFGF. HA inhibited, but conditioned medium from HA-treated HUVECs promoted, the BMP-2-mediated osteogenic differentiation of BMSCs, as indicated by the results of ALP staining and activity, ARS staining, and the mRNA expression of the osteogenic markers RUNX-2, ALP, COLI, and OPN. HA + BMP-2 (50 ng/mL) upregulated the expression of the angiogenesis-related genes VEGF and bFGF in HUVECs and bone regeneration in vivo compared to BMP-2 treatment. In conclusion, the paracrine effect of hyaluronic acid-treated endothelial cells promotes BMP-2-mediated osteogenesis, suggesting the application potential of HA + BMP-2 in bone tissue engineering. Full article

(This article belongs to the Special Issue Biomaterials for Bone Repair and Regeneration)

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21 pages, 7460 KiB

Open AccessArticle

Biocompatible MgFeCO₃ Layered Double Hydroxide (LDH) for Bone Regeneration—Low-Temperature Processing through Cold Sintering and Freeze-Casting

by Hyoung-Jun Kim, Prescillia Lagarrigue, Jae-Min Oh, Jérémy Soulié, Fabrice Salles, Sophie Cazalbou and Christophe Drouet

Bioengineering 2023, 10(6), 734; https://doi.org/10.3390/bioengineering10060734 - 19 Jun 2023

Cited by 2 | Viewed by 1814

Abstract

Layered Double Hydroxides (LDHs) are inorganic compounds of relevance to various domains, where their surface reactivity and/or intercalation capacities can be advantageously exploited for the retention/release of ionic and molecular species. In this study, we have explored specifically the applicability in the field of bone regeneration of one LDH composition, denoted “MgFeCO₃”, of which components are already present in vivo, so as to convey a biocompatibility character. The propensity to be used as a bone substitute depends, however, on their ability to allow the fabrication of 3D constructs able to be implanted in bone sites. In this work, we display two appealing approaches for the processing of MgFeCO₃ LDH particles to prepare (i) porous 3D scaffolds by freeze-casting, involving an alginate biopolymeric matrix, and (ii) pure MgFeCO₃ LDH monoliths by Spark Plasma Sintering (SPS) at low temperature. We then explored the capacity of such LDH particles or monoliths to interact quantitatively with molecular moieties/drugs in view of their local release. The experimental data were complemented by computational chemistry calculations (Monte Carlo) to examine in more detail the mineral–organic interactions at play. Finally, preliminary in vitro tests on osteoblastic MG63 cells confirmed the high biocompatible character of this LDH composition. It was confirmed that (i) thermodynamically metastable LDH could be successfully consolidated into a monolith through SPS, (ii) the LDH particles could be incorporated into a polymer matrix through freeze casting, and (iii) the LDH in the consolidated monolith could incorporate and release drug molecules in a controlled manner. In other words, our results indicate that the MgFeCO₃ LDH (pyroaurite structure) may be seen as a new promising compound for the setup of bone substitute biomaterials with tailorable drug delivery capacity, including for personalized medicine. Full article

(This article belongs to the Special Issue Biomaterials for Bone Repair and Regeneration)

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17 pages, 4727 KiB

Open AccessArticle

Dual-Crosslinking of Gelatin-Based Hydrogels: Promising Compositions for a 3D Printed Organotypic Bone Model

by Ahmer Shehzad, Fariza Mukasheva, Muhammad Moazzam, Dana Sultanova, Birzhan Abdikhan, Alexander Trifonov and Dana Akilbekova

Bioengineering 2023, 10(6), 704; https://doi.org/10.3390/bioengineering10060704 - 9 Jun 2023

Cited by 6 | Viewed by 2885

Abstract

Gelatin-based hydrogels have emerged as a popular scaffold material for tissue engineering applications. The introduction of variable crosslinking methods has shown promise for fabricating stable cell-laden scaffolds. In this work, we examine promising composite biopolymer-based inks for extrusion-based 3D bioprinting, using a dual crosslinking approach. A combination of carefully selected printable hydrogel ink compositions and the use of photoinduced covalent and ionic crosslinking mechanisms allows for the fabrication of scaffolds of high accuracy and low cytotoxicity, resulting in unimpeded cell proliferation, extracellular matrix deposition, and mineralization. Three selected bioink compositions were characterized and the respective cell-laden scaffolds were bioprinted. Temporal stability, morphology, swelling, and mechanical properties of the scaffolds were thoroughly studied and the biocompatibility of the constructs was assessed using rat mesenchymal stem cells while focusing on osteogenesis. Experimental results showed that the composition of 1% alginate, 4% gelatin, and 5% (w/v) gelatine methacrylate, was found to be optimal among the examined, with shape fidelity of 88%, large cell spreading area and cell viability at around 100% after 14 days. The large pore diameters that exceed 100 µm, and highly interconnected scaffold morphology, make these hydrogels extremely potent in bone tissue engineering and bone organoid fabrication. Full article

(This article belongs to the Special Issue Biomaterials for Bone Repair and Regeneration)

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19 pages, 3719 KiB

Open AccessArticle

Long-Bone-Regeneration Process in a Sheep Animal Model, Using Hydroxyapatite Ceramics Prepared by Tape-Casting Method

by Lenka Kresakova, Lubomir Medvecky, Katarina Vdoviakova, Maros Varga, Ján Danko, Roman Totkovic, Tatiana Spakovska, Marko Vrzgula, Maria Giretova, Jaroslav Briancin, Veronika Šimaiová and Marian Kadasi

Bioengineering 2023, 10(3), 291; https://doi.org/10.3390/bioengineering10030291 - 24 Feb 2023

Cited by 3 | Viewed by 2442

Abstract

This study was designed to investigate the effects of hydroxyapatite (HA) ceramic implants (HA cylinders, perforated HA plates, and nonperforated HA plates) on the healing of bone defects, addressing biocompatibility, biodegradability, osteoconductivity, osteoinductivity, and osteointegration with the surrounding bone tissue. The HA ceramic implants were prepared using the tape-casting method, which allows for shape variation in samples after packing HA paste into 3D-printed plastic forms. In vitro, the distribution and morphology of the MC3T3E1 cells grown on the test discs for 2 and 9 days were visualised with a fluorescent live/dead staining assay. The growth of the cell population was clearly visible on the entire ceramic surfaces and very good osteoblastic cell adhesion and proliferation was observed, with no dead cells detected. A sheep animal model was used to perform in vivo experiments with bone defects created on the metatarsal bones, where histological and immunohistochemical tissue analysis as well as X-ray and CT images were applied. After 6 months, all implants showed excellent biocompatibility with the surrounding bone tissue with no observed signs of inflammatory reaction. The histomorphological findings revealed bone growth immediately over and around the implants, indicating the excellent osteoconductivity of the HA ceramic implants. A number of islands of bone tissue were observed towards the centres of the HA cylinders. The highest degree of biodegradation, bioresorption, and new bone formation was observed in the group in which perforated HA plates were applied. The results of this study suggest that HA cylinders and HA plates may provide a promising material for the functional long-bone-defect reconstruction and further research. Full article

(This article belongs to the Special Issue Biomaterials for Bone Repair and Regeneration)

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23 pages, 4855 KiB

Open AccessArticle

Nanocrystalline Apatites: Post-Immersion Acidification and How to Avoid It—Application to Antibacterial Bone Substitutes

by Christophe Drouet, Nicolas Vandecandelaère, Anke Burger-Kentischer, Iris Trick, Christina G. Kohl, Tanja Maucher, Michaela Mueller and Franz E. Weber

Bioengineering 2023, 10(2), 220; https://doi.org/10.3390/bioengineering10020220 - 7 Feb 2023

Cited by 2 | Viewed by 1848

Abstract

Biomimetic nanocrystalline apatites analogous to bone mineral can be prepared using soft chemistry. Due to their high similarity to bone apatite, as opposed to stoichiometric hydroxyapatite for example, they now represent an appealing class of compounds to produce bioactive ceramics for which drug delivery and ion exchange abilities have been described extensively. However, immersion in aqueous media of dried non-carbonated biomimetic apatite crystals may generate an acidification event, which is often disregarded and not been clarified to-date. Yet, this acidification process could limit their further development if it is not understood and overcome if necessary. This may, for example, alter biological test outcomes, during their evaluation as bone repair materials, due to potentially deleterious effects of the acidic environment on cells, especially in in vitro static conditions. In this study, we explore the origins of this acidification phenomenon based on complementary experimental data and we point out the central role of the hydrated ionic layer present on apatite nanocrystals. We then propose a practical strategy to circumvent this acidification effect using an adequate post-precipitation equilibration step that was optimized. Using this enutralization protocol, we then showed the possibility of performing (micro)biological assessments on such compounds and provide an illustration with the examples of post-equilibrated Cu²⁺- and Ag⁺-doped nanocrystalline apatites. We demonstrate their non-cytotoxicity to osteoblast cells and their antibacterial features as tested versus five major pathogens involved in bone infections, therefore pointing to their relevance in the field of antibacterial bone substitutes. The preliminary in vivo implantation of a relevant sample in a rat’s calvarial defect confirmed its biocompatibility and the absence of adverse reaction. Understanding and eliminating this technical barrier should help promoting biomimetic apatites as a genuine new class of biomaterial-producing compounds for bone regeneration applications, e.g., with antibacterial features, far from being solely considered as “laboratory curiosities”. Full article

(This article belongs to the Special Issue Biomaterials for Bone Repair and Regeneration)

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Review

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20 pages, 7230 KiB

Open AccessReview

Bone-Regeneration Therapy Using Biodegradable Scaffolds: Calcium Phosphate Bioceramics and Biodegradable Polymers

by Kaoru Aoki, Hirokazu Ideta, Yukiko Komatsu, Atsushi Tanaka, Munehisa Kito, Masanori Okamoto, Jun Takahashi, Shuichiro Suzuki and Naoto Saito

Bioengineering 2024, 11(2), 180; https://doi.org/10.3390/bioengineering11020180 - 13 Feb 2024

Cited by 4 | Viewed by 2766

Abstract

Calcium phosphate-based synthetic bone is broadly used for the clinical treatment of bone defects caused by trauma and bone tumors. Synthetic bone is easy to use; however, its effects depend on the size and location of the bone defect. Many alternative treatment options are available, such as joint arthroplasty, autologous bone grafting, and allogeneic bone grafting. Although various biodegradable polymers are also being developed as synthetic bone material in scaffolds for regenerative medicine, the clinical application of commercial synthetic bone products with comparable performance to that of calcium phosphate bioceramics have yet to be realized. This review discusses the status quo of bone-regeneration therapy using artificial bone composed of calcium phosphate bioceramics such as β-tricalcium phosphate (βTCP), carbonate apatite, and hydroxyapatite (HA), in addition to the recent use of calcium phosphate bioceramics, biodegradable polymers, and their composites. New research has introduced potential materials such as octacalcium phosphate (OCP), biologically derived polymers, and synthetic biodegradable polymers. The performance of artificial bone is intricately related to conditions such as the intrinsic material, degradability, composite materials, manufacturing method, structure, and signaling molecules such as growth factors and cells. The development of new scaffold materials may offer more efficient bone regeneration. Full article

(This article belongs to the Special Issue Biomaterials for Bone Repair and Regeneration)

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19 pages, 1501 KiB

Open AccessReview

Paradoxical Duel Role of Collagen in Rheumatoid Arthritis: Cause of Inflammation and Treatment

by Jeevithan Elango, Camilo Zamora-Ledezma, Baolin Ge, Chunyu Hou, Zhilin Pan, Bin Bao, Carlos Pérez Albacete Martínez, José Manuel Granero Marín, José Eduardo Maté Sánchez de Val, Chunling Bao and Wenhui Wu

Bioengineering 2022, 9(7), 321; https://doi.org/10.3390/bioengineering9070321 - 15 Jul 2022

Cited by 8 | Viewed by 4858

Abstract

In biology, collagen-biomaterial regulates several signaling mechanisms of bone and immune cells involved in tissue repair and any imbalance in collagen turnover may affect the homeostasis of cells, becoming a major cause of several complications. In this case, the administration of oral collagen may play a potential role in returning cells to their normal function. For several decades, the beneficial effects of collagen have been explored widely, and thus many commercial products are available in cosmetics, food, and biomedical fields. For instance, collagen-based-products have been widely used to treat the complications of cartilage-related-disorders. Many researchers are reporting the anti-arthritogenic properties of collagen-based materials. In contrast, collagen, especially type-II collagen (CII), has been widely used to induce arthritis by immunization in an animal-model with or without adjuvants, and the potentially immunogenic-properties of collagen have been continuously reported for a long time. Additionally, the immune tolerance of collagen is mainly regulated by the T-lymphocytes and B-cells. This controversial hypothesis is getting more and more evidence nowadays from both sides to support its mechanism. Therefore, this review links the gap between the arthritogenic and anti-arthritogenic effects of collagen and explored the actual mechanism to understand the fundamental concept of collagen in arthritis. Accordingly, this review opens-up several unrevealed scientific knots of collagen and arthritis and helps the researchers understand the potential use of collagen in therapeutic applications. Full article

(This article belongs to the Special Issue Biomaterials for Bone Repair and Regeneration)

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