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Scaffolds for Bone Tissue Engineering
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Scaffolds for Bone Tissue Engineering

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

Deadline for manuscript submissions: closed (30 June 2021) | Viewed by 16145

Special Issue Editors

Prof. Dr. Susana R. Sousa

E-Mail Website
Guest Editor
Instituto de Investigação e Inovação em Saúde da Universidade do Porto, Porto, Portugal
Interests: biocomposites; tissue regeneration; extracellular matrix proteins/peptides; target-molecule delivery systems; antibacterial strategies
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Fernando Jorge Monteiro

E-Mail Website
Guest Editor
1. i3S-Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal
2. INEB-Instituto de Engenharia Biomédica, Universidade do Porto, Portugal, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal
3. FEUP-Faculdade de Engenharia da Universidade do Porto, Universidade do Porto, Rua Dr. Roberto Frias, s/n, 4200-465 Porto, Portugal
Interests: biocomposites; tissue regeneration; antibacterial strategies
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Bone disorders and conditions such as osteoporosis, bone fractures, and bone infections are increasing and are mainly linked to obesity and poor physical activity of aging populations.

Bone tissue engineering is one of the most promising strategies for the treatment of patients, as well as for active aging, using a combination of biomaterials, cells, and target molecular signals mimicking the bone microenvironment. Several 3D matrices can be applied to induce new functional bone regeneration as ceramic materials, natural polymers, and ceramic- and polymer-based biocomposites. Therefore, scaffolds for bone tissue engineering need to comply with several requirements, i.e., they must present macro-, micro-, and nanoporosity, osteoconduction, osteoinduction, and biocompatibility, among others. They should also be easy to produce and apply and have a reasonable shelf-life, and they should be cost-effective. The field is rapidly evolving into new areas of innovation.

Following our nomination as Editors of a Special Issue of the Journal Materials, published by MDPI and dedicated to “Scaffolds for Bone Tissue Engineering”, it is our pleasure to invite you to submit a manuscript for this Special Issue. Full papers, communications, and reviews are all welcome.

Prof. Dr. Susana Sousa
Prof. Dr. Fernando Jorge Monteiro
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. Materials is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). 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

  • scaffolds
  • bone tissue engineering
  • bone regeneration
  • bone infection
  • antibacterial materials
  • ceramic-based biomaterials

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Published Papers (5 papers)

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Research

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22 pages, 12451 KiB  
Article
Bioengineered Fluorescent Nanoprobe Conjugates for Tracking Human Bone Cells: In Vitro Biocompatibility Analysis
by Christiane L. Salgado, Alexandra A. P. Mansur, Herman S. Mansur and Fernando J. M. Monteiro
Materials 2021, 14(16), 4422; https://doi.org/10.3390/ma14164422 - 7 Aug 2021
Cited by 5 | Viewed by 2072
Abstract
Herein, we validated novel functionalized hybrid semiconductor bioconjugates made of fluorescent quantum dots (QD) with the surface capped by chitosan (polysaccharide) and chemically modified with O-phospho-L-serine (OPS) that are biocompatible with different human cell sources. The conjugation with a directing signaling molecule (OPS) [...] Read more.
Herein, we validated novel functionalized hybrid semiconductor bioconjugates made of fluorescent quantum dots (QD) with the surface capped by chitosan (polysaccharide) and chemically modified with O-phospho-L-serine (OPS) that are biocompatible with different human cell sources. The conjugation with a directing signaling molecule (OPS) allows preferential accumulation in human bone mesenchymal stromal cells (HBMSC). The chitosan (Chi) shell with the fluorescent CdS core was characterized by spectroscopical (UV spectrophotometry and photoluminescence), by morphological techniques (Transmission Electron Microscopy (TEM)) and showed small size (ø 2.3 nm) and a stable photoluminescence emission band. The in vitro biocompatibility results were not dependent on the polysaccharide chain length (Chi with higher and lower molecular weight) but were remarkably affected by the surface modification (Chi or Chi-OPS). In addition, the efficiency of nanoparticles uptake by the cells was dependent on cells nature (human primary cells or cell lines) and tissue source (bone or skin) in the presence or absence of the OPS modification. The complex cellular uptake pathways involved in the cell labeling with the nanoparticles do not interfere on the normal cellular biology (adhesion and proliferation), osteogenic differentiation, and gene expression. The bone cells particles uptake evaluation showed a possible pathway by Caveolin-1 that regulates cell transduction in the membrane’s Caveolae. Caveolae mediates non-specific endocytosis, and it is upregulated in HBMSC. The OPS-modified nanoparticles promoted an intense intracellular trafficking by the HBMSCs that showed late-osteoblast phenotype with an increase of extracellular matrix (ECM) mineralization (Alizarin red and Von Kossa staining for calcium phosphate crystals). In this work, the OPS modified bioconjugated QD proved to be a reliable and stable fluorescent bioprobe for cell imaging and targeting research that could also help in clarifying some cellular mechanisms of particles intracellular traffic through the cytoplasmic membrane and osteogenic differentiation induction. The in vitro HBMSC’s biocompatibility responses indicated that the OPS-modified chitosan QDs have a prospective future in laboratory and pre-clinical applications such as bioimaging analysis and for ex-vivo cellular evaluation of biomedical implants. Full article
(This article belongs to the Special Issue Scaffolds for Bone Tissue Engineering)
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19 pages, 5828 KiB  
Article
Translational Research for Orthopedic Bone Graft Development
by Maria J. C. Vilela, Bruno J. A. Colaço, José Ventura, Fernando J. M. Monteiro and Christiane L. Salgado
Materials 2021, 14(15), 4130; https://doi.org/10.3390/ma14154130 - 24 Jul 2021
Cited by 5 | Viewed by 2929
Abstract
Designing biomaterials for bone-substitute applications is still a challenge regarding the natural complex structure of hard tissues. Aiming at bone regeneration applications, scaffolds based on natural collagen and synthetic nanohydroxyapatite were developed, and they showed adequate mechanical and biological properties. The objective of [...] Read more.
Designing biomaterials for bone-substitute applications is still a challenge regarding the natural complex structure of hard tissues. Aiming at bone regeneration applications, scaffolds based on natural collagen and synthetic nanohydroxyapatite were developed, and they showed adequate mechanical and biological properties. The objective of this work was to perform and evaluate a scaled-up production process of this porous biocomposite scaffold, which promotes bone regeneration and works as a barrier for both fibrosis and the proliferation of scar tissue. The material was produced using a prototype bioreactor at an industrial scale, instead of laboratory production at the bench, in order to produce an appropriate medical device for the orthopedic market. Prototypes were produced in porous membranes that were e-beam irradiated (the sterilization process) and then analysed by scanning electron microscopy (SEM), confocal laser scanning microscopy (CLSM), dynamic mechanical analysis (DMA), cytotoxicity tests with mice fibroblasts (L929), human osteoblast-like cells (MG63) and human MSC osteogenic differentiation (HBMSC) with alkaline phosphatase (ALP) activity and qPCR for osteogenic gene expression. The prototypes were also implanted into critical-size bone defects (rabbits’ tibia) for 5 and 15 weeks, and after that were analysed by microCT and histology. The tests performed for the physical characterization of the materials showed the ability of the scaffolds to absorb and retain water-based solvents, as well as adequate mechanical resistance and viscoelastic properties. The cryogels had a heteroporous morphology with microporosity and macroporosity, which are essential conditions for the interaction between the cells and materials, and which consequently promote bone regeneration. Regarding the biological studies, all of the studied cryogels were non-cytotoxic by direct or indirect contact with cells. In fact, the scaffolds promoted the proliferation of the human MSCs, as well as the expression of the osteoblastic phenotype (osteogenic differentiation). The in vivo results showed bone tissue ingrowth and the materials’ degradation, filling the critical bone defect after 15 weeks. Before and after irradiation, the studied scaffolds showed similar properties when compared to the results published in the literature. In conclusion, the material production process upscaling was optimized and the obtained prototypes showed reproducible properties relative to the bench development, and should be able to be commercialized. Therefore, it was a successful effort to harness knowledge from the basic sciences to produce a new biomedical device and enhance human health and wellbeing. Full article
(This article belongs to the Special Issue Scaffolds for Bone Tissue Engineering)
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19 pages, 3788 KiB  
Article
An Antibiotic-Releasing Bone Void Filling (ABVF) Putty for the Treatment of Osteomyelitis
by Raquib Hasan, Abbey Wohlers, Jacob Shreffler, Pranothi Mulinti, Hunter Ostlie, Codi Schaper, Benjamin Brooks and Amanda Brooks
Materials 2020, 13(22), 5080; https://doi.org/10.3390/ma13225080 - 11 Nov 2020
Cited by 8 | Viewed by 3132
Abstract
The number of total joint replacements (TJR) is on the rise with a corresponding increase in the number of infected TJR, which necessitates revision surgeries. Current treatments with either non-biodegradable, antibiotic-releasing polymethylmethacrylate (PMMA) based bone cement, or systemic antibiotic after surgical debridement do [...] Read more.
The number of total joint replacements (TJR) is on the rise with a corresponding increase in the number of infected TJR, which necessitates revision surgeries. Current treatments with either non-biodegradable, antibiotic-releasing polymethylmethacrylate (PMMA) based bone cement, or systemic antibiotic after surgical debridement do not provide effective treatment due to fluctuating antibiotic levels at the site of infection. Here, we report a biodegradable, easy-to-use “press-fitting” antibiotic-releasing bone void filling (ABVF) putty that not only provides efficient antibiotic release kinetics at the site of infection but also allows efficient osseointegration. The ABVF formulation was prepared using poly (D,L-lactide-co-glycolide) (PLGA), polyethylene glycol (PEG), and polycaprolactone (PCL) as the polymer matrix, antibiotic vancomycin, and osseointegrating synthetic bone PRO OSTEON for bone-growth support. ABVF was homogenous, had a porous structure, was moldable, and showed putty-like mechanical properties. The ABVF putty released vancomycin for 6 weeks at therapeutic level. Furthermore, the released vancomycin showed in vitro antibacterial activity against Staphylococcus aureus for 6 weeks. Vancomycin was not toxic to osteoblasts. Finally, ABVF was biodegradable in vivo and showed an effective infection control with the treatment group showing significantly higher bone growth (p < 0.001) compared to the control group. The potential of infection treatment and osseointegration makes the ABVF putty a promising treatment option for osteomyelitis after TJR. Full article
(This article belongs to the Special Issue Scaffolds for Bone Tissue Engineering)
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20 pages, 5856 KiB  
Article
Titanium Dioxide Thin Films Obtained by Atomic Layer Deposition Promotes Osteoblasts’ Viability and Differentiation Potential While Inhibiting Osteoclast Activity—Potential Application for Osteoporotic Bone Regeneration
by Agnieszka Smieszek, Aleksandra Seweryn, Klaudia Marcinkowska, Mateusz Sikora, Krystyna Lawniczak-Jablonska, Bartlomiej. S. Witkowski, Piotr Kuzmiuk, Marek Godlewski and Krzysztof Marycz
Materials 2020, 13(21), 4817; https://doi.org/10.3390/ma13214817 - 28 Oct 2020
Cited by 18 | Viewed by 2690
Abstract
Atomic layer deposition (ALD) technology has started to attract attention as an efficient method for obtaining bioactive, ultrathin oxide coatings. In this study, using ALD, we have created titanium dioxide (TiO2) layers. The coatings were characterised in terms of physicochemical and [...] Read more.
Atomic layer deposition (ALD) technology has started to attract attention as an efficient method for obtaining bioactive, ultrathin oxide coatings. In this study, using ALD, we have created titanium dioxide (TiO2) layers. The coatings were characterised in terms of physicochemical and biological properties. The chemical composition of coatings, as well as thickness, roughness, wettability, was determined using XPS, XRD, XRR. Cytocompatibillity of ALD TiO2 coatings was accessed applying model of mouse pre-osteoblast cell line MC3T3-E1. The accumulation of transcripts essential for bone metabolism (both mRNA and miRNA) was determined using RT-qPCR. Obtained ALD TiO2 coatings were characterised as amorphous and homogeneous. Cytocompatibility of the layers was expressed by proper morphology and growth pattern of the osteoblasts, as well as their increased viability, proliferative and metabolic activity. Simultaneously, we observed decreased activity of osteoclasts. Obtained coatings promoted expression of Opn, Coll-1, miR-17 and miR-21 in MC3T3-E1 cells. The results are promising in terms of the potential application of TiO2 coatings obtained by ALD in the field of orthopaedics, especially in terms of metabolic- and age-related bone diseases, including osteoporosis. Full article
(This article belongs to the Special Issue Scaffolds for Bone Tissue Engineering)
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Review

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17 pages, 1273 KiB  
Review
The State of Starch/Hydroxyapatite Composite Scaffold in Bone Tissue Engineering with Consideration for Dielectric Measurement as an Alternative Characterization Technique
by Mohd Riza Mohd Roslan, Nadhiya Liyana Mohd Kamal, Muhammad Farid Abdul Khalid, Nashrul Fazli Mohd Nasir, Ee Meng Cheng, Chong You Beh, Joo Shun Tan and Mohd Shamzi Mohamed
Materials 2021, 14(8), 1960; https://doi.org/10.3390/ma14081960 - 14 Apr 2021
Cited by 26 | Viewed by 4302
Abstract
Hydroxyapatite (HA) has been widely used as a scaffold in tissue engineering. HA possesses high mechanical stress and exhibits particularly excellent biocompatibility owing to its similarity to natural bone. Nonetheless, this ceramic scaffold has limited applications due to its apparent brittleness. Therefore, this [...] Read more.
Hydroxyapatite (HA) has been widely used as a scaffold in tissue engineering. HA possesses high mechanical stress and exhibits particularly excellent biocompatibility owing to its similarity to natural bone. Nonetheless, this ceramic scaffold has limited applications due to its apparent brittleness. Therefore, this had presented some difficulties when shaping implants out of HA and for sustaining a high mechanical load. Fortunately, these drawbacks can be improved by combining HA with other biomaterials. Starch was heavily considered for biomedical device applications in favor of its low cost, wide availability, and biocompatibility properties that complement HA. This review provides an insight into starch/HA composites used in the fabrication of bone tissue scaffolds and numerous factors that influence the scaffold properties. Moreover, an alternative characterization of scaffolds via dielectric and free space measurement as a potential contactless and nondestructive measurement method is also highlighted. Full article
(This article belongs to the Special Issue Scaffolds for Bone Tissue Engineering)
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