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Biomaterials for Bone Tissue Engineering 2020

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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 (10 November 2022) | Viewed by 38271

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Dr. Nora Bloise

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Department of Molecular Medicine, Biochemistry Unit, University of Pavia, Viale Taramelli 3/b, 27100 Pavia, Italy
Interests: bone regeneration; biomaterials; mesenchymal stem cell differentiation, cell–biomaterial interaction; bone regeneration; cell culture; molecular biology; cell biology; tissue engineering; biocompatibility; scaffolds; nanomaterials; cellular mechanisms
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Dr. Lorenzo Fassina

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Department of Electrical, Computer and Biomedical Engineering, University of Pavia, Via Ferrata 5, 27100 Pavia, Italy
Interests: tissue engineering via biomaterials and physical stimuli
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Special Issue Information

Dear Colleagues,

Over the last few decades, a variety of tissue engineering strategies have been developed to improve the regenerative properties of bone biomaterials (e.g., osteoinduction and osteoconduction). This Special Issue on “Biomaterials for Bone Tissue Engineering” will provide an overview of the recent advances and cutting-edge approaches in the field of bone biomaterials and bone tissue engineering, including the new molecular insights on the various aspects of the interaction of bone substitutes with cells and tissues. Contributions reporting innovative materials, osteoinduction and osteoconduction approaches, and examples of combination with biochemical and/or physical stimuli and/or different cell types (e.g., stem cells, macrophages, endothelial cells) tested for their application in bone tissue regeneration and engineering are welcome.

Thus, we invite the submission of original full papers, communications, and comprehensive reviews describing the latest progress.

Best Regards,

Dr. Nora Bloise
Dr. Lorenzo Fassina
Guest Editors

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Keywords

bone regeneration
bone tissue engineering in vitro and in vivo
bone substitutes
bone marrow stem cells
adipose derived stem cells
growth factors
cell/tissue–biomaterials interaction
physical stimuli (ultrasound, laser, electric or electromagnetic field, shear stress, etc.)
bioreactors
molecular mechanisms

Related Special Issue

Biomaterials for Bone Tissue Engineering (Second Volume) in Materials (3 articles)

Published Papers (12 papers)

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Research

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17 pages, 4637 KiB

Open AccessArticle

Mineralization in a Critical Size Bone-Gap in Sheep Tibia Improved by a Chitosan-Calcium Phosphate-Based Composite as Compared to Predicate Device

by Gissur Örlygsson, Elín H. Laxdal, Sigurbergur Kárason, Atli Dagbjartsson, Eggert Gunnarsson, Chuen-How Ng, Jón M. Einarsson, Jóhannes Gíslason and Halldór Jónsson, Jr.

Materials 2022, 15(3), 838; https://0-doi-org.brum.beds.ac.uk/10.3390/ma15030838 - 22 Jan 2022

Cited by 5 | Viewed by 2085

Abstract

Deacetylated chitin derivatives have been widely studied for tissue engineering purposes. This study aimed to compare the efficacy of an injectable product containing a 50% deacetylated chitin derivative (BoneReg-Inject™) and an existing product (chronOS Inject^®) serving as a predicate device. A sheep model with a critical size drill hole in the tibial plateau was used. Holes of 8 mm diameter and 30 mm length were drilled bilaterally into the proximal area of the tibia and BoneReg-Inject™ or chronOS Inject^® were injected into the right leg holes. Comparison of resorption and bone formation in vivo was made by X-ray micro-CT and histological evaluation after a live phase of 12 weeks. Long-term effects of BoneReg-Inject™ were studied using a 13-month live period. Significant differences were observed in (1) amount of new bone within implant (p < 0.001), higher in BoneReg-Inject^TM, (2) signs of cartilage tissue (p = 0.003), more pronounced in BoneReg-Inject^TM, and (3) signs of fibrous tissue (p < 0.001), less pronounced in BoneReg-Inject^TM. Mineral content at 13 months postoperative was significantly higher than at 12 weeks (p < 0.001 and p < 0.05, for implant core and rim, respectively). The data demonstrate the potential of deacetylated chitin derivatives to stimulate bone formation. Full article

(This article belongs to the Special Issue Biomaterials for Bone Tissue Engineering 2020)

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11 pages, 3953 KiB

Open AccessArticle

Sol–Gel Synthesis and Characterization of a Quaternary Bioglass for Bone Regeneration and Tissue Engineering

by Ricardo Bento, Anuraag Gaddam and José M. F. Ferreira

Materials 2021, 14(16), 4515; https://0-doi-org.brum.beds.ac.uk/10.3390/ma14164515 - 11 Aug 2021

Cited by 11 | Viewed by 2609

Abstract

Sol–gel synthesis using inorganic and/or organic precursors that undergo hydrolysis and condensation at room temperature is a very attractive and less energetic method for preparing bioactive glass (BG) compositions, as an alternative to the melt-quenching process. When properly conducted, sol–gel synthesis might result in amorphous structures, with all of the components intimately mixed at the atomic scale. Moreover, developing new and better performing materials for bone tissue engineering is a growing concern, as the aging of the world’s population leads to lower bone density and osteoporosis. This work describes the sol–gel synthesis of a novel quaternary silicate-based BG with the composition 60 SiO₂–34 CaO–4 MgO–2 P₂O₅ (mol%), which was prepared using acidified distilled water as a single solvent. By controlling the kinetics of the hydrolysis and condensation steps, an amorphous glass structure could be obtained. The XRD results of samples calcined within the temperature range of 600–900 °C demonstrated that the amorphous nature was maintained until 800 °C, followed by partial crystallization at 900 °C. The specific surface area—an important factor in osteoconduction—was also evaluated over different temperatures, ranging from 160.6 ± 0.8 m²/g at 600 °C to 2.2 ± 0.1 m²/g at 900 °C, accompanied by consistent changes in average pore size and pore size distribution. The immersion of the BG particles in simulated body fluid (SBF) led to the formation of an extensive apatite layer on its surface. These overall results indicate that the proposed material is very promising for biomedical applications in bone regeneration and tissue engineering. Full article

(This article belongs to the Special Issue Biomaterials for Bone Tissue Engineering 2020)

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17 pages, 7092 KiB

Open AccessArticle

Human Olfactory Mucosa Stem Cells Delivery Using a Collagen Hydrogel: As a Potential Candidate for Bone Tissue Engineering

by Sara Simorgh, Peiman Brouki Milan, Maryam Saadatmand, Zohreh Bagher, Mazaher Gholipourmalekabadi, Rafieh Alizadeh, Ahmad Hivechi, Zohreh Arabpour, Masoud Hamidi and Cédric Delattre

Materials 2021, 14(14), 3909; https://0-doi-org.brum.beds.ac.uk/10.3390/ma14143909 - 13 Jul 2021

Cited by 30 | Viewed by 2653

Abstract

For bone tissue engineering, stem cell-based therapy has become a promising option. Recently, cell transplantation supported by polymeric carriers has been increasingly evaluated. Herein, we encapsulated human olfactory ectomesenchymal stem cells (OE-MSC) in the collagen hydrogel system, and their osteogenic potential was assessed in vitro and in vivo conditions. Collagen type I was composed of four different concentrations of (4 mg/mL, 5 mg/mL, 6 mg/mL, 7 mg/mL). SDS-Page, FTIR, rheologic test, resazurin assay, live/dead assay, and SEM were used to characterize collagen hydrogels. OE-MSCs encapsulated in the optimum concentration of collagen hydrogel and transplanted in rat calvarial defects. The tissue samples were harvested after 4- and 8-weeks post-transplantation and assessed by optical imaging, micro CT, and H&E staining methods. The highest porosity and biocompatibility were confirmed in all scaffolds. The collagen hydrogel with 7 mg/mL concentration was presented as optimal mechanical properties close to the naïve bone. Furthermore, the same concentration illustrated high osteogenic differentiation confirmed by real-time PCR and alizarin red S methods. Bone healing has significantly occurred in defects treated with OE-MSCs encapsulated hydrogels in vivo. As a result, OE-MSCs with suitable carriers could be used as an appropriate cell source to address clinical bone complications. Full article

(This article belongs to the Special Issue Biomaterials for Bone Tissue Engineering 2020)

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20 pages, 7323 KiB

Open AccessFeature PaperArticle

Topological, Mechanical and Biological Properties of Ti6Al4V Scaffolds for Bone Tissue Regeneration Fabricated with Reused Powders via Electron Beam Melting

by Maria Laura Gatto, Riccardo Groppo, Nora Bloise, Lorenzo Fassina, Livia Visai, Manuela Galati, Luca Iuliano and Paolo Mengucci

Materials 2021, 14(1), 224; https://0-doi-org.brum.beds.ac.uk/10.3390/ma14010224 - 05 Jan 2021

Cited by 30 | Viewed by 3106

Abstract

Cellularized scaffold is emerging as the preferred solution for tissue regeneration and restoration of damaged functionalities. However, the high cost of preclinical studies creates a gap between investigation and the device market for the biomedical industry. In this work, bone-tailored scaffolds based on the Ti6Al4V alloy manufactured by electron beam melting (EBM) technology with reused powder were investigated, aiming to overcome issues connected to the high cost of preclinical studies. Two different elementary unit cell scaffold geometries, namely diamond (DO) and rhombic dodecahedron (RD), were adopted, while surface functionalization was performed by coating scaffolds with single layers of polycaprolactone (PCL) or with mixture of polycaprolactone and 20 wt.% hydroxyapatite (PCL/HA). The mechanical and biological performances of the produced scaffolds were investigated, and the results were compared to software simulation and experimental evidence available in literature. Good mechanical properties and a favorable environment for cell growth were obtained for all combinations of scaffold geometry and surface functionalization. In conclusion, powder recycling provides a viable practice for the biomedical industry to strongly reduce preclinical costs without altering biomechanical performance. Full article

(This article belongs to the Special Issue Biomaterials for Bone Tissue Engineering 2020)

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15 pages, 7948 KiB

Open AccessArticle

Histological and Histomorphometric Analyses of Bone Regeneration in Osteoporotic Rats Using a Xenograft Material

by Marwa Y. Shaheen, Amani M. Basudan, Abdurahman A. Niazy, Jeroen J. J. P. van den Beucken, John A. Jansen and Hamdan S. Alghamdi

Materials 2021, 14(1), 222; https://0-doi-org.brum.beds.ac.uk/10.3390/ma14010222 - 05 Jan 2021

Cited by 3 | Viewed by 2329

Abstract

We evaluated the effect of osteoporotic induction after eight weeks of initial healing of bone defects grafted with a xenograft material in a rat model. Bone defects were created in the femoral condyles of 16 female Wistar rats (one defect per rat). The defects were filled with bovine bone (Inter-Oss) granules. After eight weeks of bone healing, rats were randomly ovariectomized (OVX) or sham-operated (SHAM). At 14 weeks of bone healing, all animals were euthanized. Bone specimens were harvested and processed for histological and histomorphometric analyses to assess new bone formation (N-BF%), remaining bone graft (RBG%) and trabecular bone space (Tb.Sp%) within the defect area. After 14 weeks of bone healing, histological evaluation revealed a significant alteration in trabecular bone in OVX rats compared to SHAM rats. There was lower N-BF% in OVX rats (22.5% ± 3.0%) compared to SHAM rats (37.7% ± 7.9%; p < 0.05). Additionally, the RBG% was significantly lower in OVX (23.7% ± 5.8%) compared to SHAM (34.8% ± 9.6%; p < 0.05) rats. Finally, the Tb.Sp% was higher in OVX (53.8% ± 7.7%) compared to SHAM (27.5% ± 14.3%; p < 0.05) rats. In conclusion, within the limitations of this study, inducing an osteoporotic condition in a rat model negatively influenced bone regeneration in the created bone defect and grafted with a xenograft material. Full article

(This article belongs to the Special Issue Biomaterials for Bone Tissue Engineering 2020)

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13 pages, 3678 KiB

Open AccessArticle

Histomorphometric Evaluation of Peri-Implant Bone Response to Intravenous Administration of Zoledronate (Zometa^®) in an Osteoporotic Rat Model

by Amani M. Basudan, Marwa Y. Shaheen, Abdurahman A. Niazy, Jeroen J. J. P. van den Beucken, John A. Jansen and Hamdan S. Alghamdi

Materials 2020, 13(22), 5248; https://0-doi-org.brum.beds.ac.uk/10.3390/ma13225248 - 20 Nov 2020

Cited by 2 | Viewed by 1552

Abstract

We evaluated the response to peri-implant bone placed in the femoral condyle of osteoporotic rats, following intravenous zoledronate (ZOL) treatment in three settings: pre-implantation (ZOL-Pre), post-implantation (ZOL-Post), and pre- + post-implantation (ZOL-Pre+Post). Twenty-four female Wistar rats were ovariectomized (OVX). After 12 weeks, the rats received titanium implants in the right femoral condyle. ZOL (0.04 mg/kg, weekly) was administered to six rats 4 weeks pre-implantation and was stopped at implant placement. To another six rats, ZOL was given post-implantation and continued for 6 weeks. Additional six rats received ZOL treatment pre- and post-implantation. Control animals received weekly saline intravenous injections. At 6 weeks post-implantation, samples were retrieved for histological evaluation of the percentage of bone area (%BA) and of the percentage of bone-to-implant contact (%BIC). BA% for ZOL-Pre (29.6% ± 9.0%) and ZOL-Post (27.9% ± 5.6%) rats were significantly increased compared to that of the controls (17.3% ± 3.9%, p < 0.05). In contrast, ZOL-Pre+Post rats (20.4% ± 5.0%) showed similar BA% compared to Saline controls (p = 0.731). BIC% revealed a significant increase for ZOL-Post (65.8% ± 16.9%) and ZOL-Pre+Post (68.3% ± 10.0%) rats compared with that of Saline controls (43.3% ± 9.6%, p < 0.05), while ZOL-Pre rats (55.6% ± 19%) showed a BIC% comparable to that of Saline controls (p = 0.408). Our results suggest that receiving intravenous ZOL treatment before or after implant placement enhances peri-implant bone responses in terms of bone area. However, the effect of different ZOL treatment regimens on BIC% was found to be inconclusive. Full article

(This article belongs to the Special Issue Biomaterials for Bone Tissue Engineering 2020)

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16 pages, 4240 KiB

Open AccessArticle

Evaluation of Osteoconduction of a Synthetic Hydroxyapatite/β-Tricalcium Phosphate Block Fixed in Rabbit Mandibles

by Luis Carlos de Almeida Pires, Rodrigo Capalbo da Silva, Pier Paolo Poli, Fernando Ruas Esgalha, Henrique Hadad, Letícia Pitol Palin, Ana Flávia Piquera Santos, Luara Teixiera Colombo, Laís Kawamata de Jesus, Ana Paula Farnezi Bassi, Carlo Maiorana, Roberta Okamoto, Paulo Sérgio Perri de Carvalho and Francisley Ávila Souza

Materials 2020, 13(21), 4902; https://0-doi-org.brum.beds.ac.uk/10.3390/ma13214902 - 31 Oct 2020

Cited by 3 | Viewed by 2153

Abstract

(1) Background: This study aimed to evaluate the incorporation of hydroxyapatite/β-tricalcium phosphate blocks grafted in rabbit mandibles. (2) Methods: Topographic characterization of biomaterial was performed through scanning electron microscopy coupled with energy-dispersive X-ray spectroscopy (SEM-EDX). Ten rabbits randomly received autogenous bone graft harvested from the tibia (Autogenous Group—AG) or synthetic biomaterial manufactured in β-tricalcium phosphate (Biomaterial Group—BG) at their right and left mandibular angles. Euthanasia was performed at 30 and 60 postoperative days; (3) Results: SEM-EDX showed a surface with the formation of crystals clusters. Histological analyses in BG at 30 days showed a slower process of incorporation than AG. At 60 days, BG showed remnants of biomaterial enveloped by bone tissue in the anabolic modeling phase. Histometric analysis showed that mean values of newly formed bone-like tissue in the AG (6.56%/9.70%) were statistically higher compared to BG (3.14%/6.43%) in both periods, respectively. Immunohistochemical analysis demonstrated early bone formation and maturation in the AG with more intense osteopontin and osteocalcin staining. (4) Conclusions: The biomaterial proved to be a possible bone substitute, being incorporated into the receiving bed; however, it showed delayed bone incorporation compared to autogenous bone. Full article

(This article belongs to the Special Issue Biomaterials for Bone Tissue Engineering 2020)

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21 pages, 6919 KiB

Open AccessArticle

In Vitro Production of Calcified Bone Matrix onto Wool Keratin Scaffolds via Osteogenic Factors and Electromagnetic Stimulus

by Nora Bloise, Alessia Patrucco, Giovanna Bruni, Giulia Montagna, Rosalinda Caringella, Lorenzo Fassina, Claudio Tonin and Livia Visai

Materials 2020, 13(14), 3052; https://0-doi-org.brum.beds.ac.uk/10.3390/ma13143052 - 08 Jul 2020

Cited by 28 | Viewed by 2854

Abstract

Pulsed electromagnetic field (PEMF) has drawn attention as a potential tool to improve the ability of bone biomaterials to integrate into the surrounding tissue. We investigated the effects of PEMF (frequency, 75 Hz; magnetic induction amplitude, 2 mT; pulse duration, 1.3 ms) on human osteoblast-like cells (SAOS-2) seeded onto wool keratin scaffolds in terms of proliferation, differentiation, and production of the calcified bone extracellular matrix. The wool keratin scaffold offered a 3D porous architecture for cell guesting and nutrient diffusion, suggesting its possible use as a filler to repair bone defects. Here, the combined approach of applying a daily PEMF exposure with additional osteogenic factors stimulated the cells to increase both the deposition of bone-related proteins and calcified matrix onto the wool keratin scaffolds. Also, the presence of SAOS-2 cells, or PEMF, or osteogenic factors did not influence the compression behavior or the resilience of keratin scaffolds in wet conditions. Besides, ageing tests revealed that wool keratin scaffolds were very stable and showed a lower degradation rate compared to commercial collagen sponges. It is for these reasons that this tissue engineering strategy, which improves the osteointegration properties of the wool keratin scaffold, may have a promising application for long term support of bone formation in vivo. Full article

(This article belongs to the Special Issue Biomaterials for Bone Tissue Engineering 2020)

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14 pages, 1943 KiB

Open AccessArticle

Utilizing Osteocyte Derived Factors to Enhance Cell Viability and Osteogenic Matrix Deposition within IPN Hydrogels

by Laurens Parmentier, Mathieu Riffault and David A. Hoey

Materials 2020, 13(7), 1690; https://0-doi-org.brum.beds.ac.uk/10.3390/ma13071690 - 04 Apr 2020

Cited by 10 | Viewed by 2991

Abstract

Many bone defects arising due to traumatic injury, disease, or surgery are unable to regenerate, requiring intervention. More than four million graft procedures are performed each year to treat these defects making bone the second most commonly transplanted tissue worldwide. However, these types of graft suffer from a limited supply, a second surgical site, donor site morbidity, and pain. Due to the unmet clinical need for new materials to promote skeletal repair, this study aimed to produce novel biomimetic materials to enhance stem/stromal cell osteogenesis and bone repair by recapitulating aspects of the biophysical and biochemical cues found within the bone microenvironment. Utilizing a collagen type I–alginate interpenetrating polymer network we fabricated a material which mirrors the mechanical and structural properties of unmineralized bone, consisting of a porous fibrous matrix with a young’s modulus of 64 kPa, both of which have been shown to enhance mesenchymal stromal/stem cell (MSC) osteogenesis. Moreover, by combining this material with biochemical paracrine factors released by statically cultured and mechanically stimulated osteocytes, we further mirrored the biochemical environment of the bone niche, enhancing stromal/stem cell viability, differentiation, and matrix deposition. Therefore, this biomimetic material represents a novel approach to promote skeletal repair. Full article

(This article belongs to the Special Issue Biomaterials for Bone Tissue Engineering 2020)

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Review

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29 pages, 1516 KiB

Open AccessReview

A Multidisciplinary Journey towards Bone Tissue Engineering

by Sara G. Pedrero, Pilar Llamas-Sillero and Juana Serrano-López

Materials 2021, 14(17), 4896; https://0-doi-org.brum.beds.ac.uk/10.3390/ma14174896 - 28 Aug 2021

Cited by 17 | Viewed by 4325

Abstract

Millions of patients suffer yearly from bone fractures and disorders such as osteoporosis or cancer, which constitute the most common causes of severe long-term pain and physical disabilities. The intrinsic capacity of bone to repair the damaged bone allows normal healing of most small bone injuries. However, larger bone defects or more complex diseases require additional stimulation to fully heal. In this context, the traditional routes to address bone disorders present several associated drawbacks concerning their efficacy and cost-effectiveness. Thus, alternative therapies become necessary to overcome these limitations. In recent decades, bone tissue engineering has emerged as a promising interdisciplinary strategy to mimic environments specifically designed to facilitate bone tissue regeneration. Approaches developed to date aim at three essential factors: osteoconductive scaffolds, osteoinduction through growth factors, and cells with osteogenic capability. This review addresses the biological basis of bone and its remodeling process, providing an overview of the bone tissue engineering strategies developed to date and describing the mechanisms that underlie cell–biomaterial interactions. Full article

(This article belongs to the Special Issue Biomaterials for Bone Tissue Engineering 2020)

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41 pages, 4433 KiB

Open AccessReview

Titanium and Protein Adsorption: An Overview of Mechanisms and Effects of Surface Features

by Jacopo Barberi and Silvia Spriano

Materials 2021, 14(7), 1590; https://0-doi-org.brum.beds.ac.uk/10.3390/ma14071590 - 24 Mar 2021

Cited by 87 | Viewed by 7134

Abstract

Titanium and its alloys, specially Ti6Al4V, are among the most employed materials in orthopedic and dental implants. Cells response and osseointegration of implant devices are strongly dependent on the body–biomaterial interface zone. This interface is mainly defined by proteins: They adsorb immediately after implantation from blood and biological fluids, forming a layer on implant surfaces. Therefore, it is of utmost importance to understand which features of biomaterials surfaces influence formation of the protein layer and how to guide it. In this paper, relevant literature of the last 15 years about protein adsorption on titanium-based materials is reviewed. How the surface characteristics affect protein adsorption is investigated, aiming to provide an as comprehensive a picture as possible of adsorption mechanisms and type of chemical bonding with the surface, as well as of the characterization techniques effectively applied to model and real implant surfaces. Surface free energy, charge, microroughness, and hydroxylation degree have been found to be the main surface parameters to affect the amount of adsorbed proteins. On the other hand, the conformation of adsorbed proteins is mainly dictated by the protein structure, surface topography at the nano-scale, and exposed functional groups. Protein adsorption on titanium surfaces still needs further clarification, in particular concerning adsorption from complex protein solutions. In addition, characterization techniques to investigate and compare the different aspects of protein adsorption on different surfaces (in terms of roughness and chemistry) shall be developed. Full article

(This article belongs to the Special Issue Biomaterials for Bone Tissue Engineering 2020)

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11 pages, 1558 KiB

Open AccessReview

Evaluation of Bone Gain and Complication Rates after Guided Bone Regeneration with Titanium Foils: A Systematic Review

by Elisabet Roca-Millan, Enric Jané-Salas, Albert Estrugo-Devesa and José López-López

Materials 2020, 13(23), 5346; https://0-doi-org.brum.beds.ac.uk/10.3390/ma13235346 - 25 Nov 2020

Cited by 13 | Viewed by 2658

Abstract

Guided bone regeneration techniques are increasingly used to enable the subsequent placement of dental implants. This systematic review aims to analyze the success rate of these techniques in terms of bone gain and complications rate using titanium membranes as a barrier element. Electronic and hand searches were conducted in PubMed/Medline, Scielo, Scopus and Cochrane Library databases for case reports, case series, cohort studies and clinical trials in humans published up to and including 19 September 2020. Thirteen articles were included in the qualitative analysis. Bone gain both horizontally and vertically was comparable to that obtained with other types of membranes more commonly used. The postoperative complication rate was higher that of native collagen membranes and non-resorbable titanium-reinforced membranes, and similar that of crosslinked collagen membranes and titanium meshes. The survival rate of the implants was similar to that of implants placed in native bone. Due to the limited scientific literature published on this issue, more randomized clinical trials comparing occlusive titanium barriers and other types of membranes are necessary to reach more valid conclusions. Full article

(This article belongs to the Special Issue Biomaterials for Bone Tissue Engineering 2020)

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