Special Issue "Design of Materials for Bone Tissue Scaffolds"

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

Deadline for manuscript submissions: 31 May 2021.

Special Issue Editor

Prof. Dr. Antonio Boccaccio
E-Mail Website
Guest Editor
Dipartimento di Meccanica, Matematica e Management (DMMM), Politecnico di Bari, Via E. Orabona 4, 70126 Bari, Italy
Interests: bioengineering; morphological optimization of biomaterials; modeling and simulation of biomedical devices and mechanobiological processes; optical techniques for reverse engineering; characterization of biomedical materials

Special Issue Information

Dear Colleagues,

The recent development of additive manufacturing techniques has allowed the building of regular scaffolds made from a very wide gamma of biocompatible materials and including complex and sophisticated geometries that can be optimized to increase the scaffold performance in terms of mechanical resistance and mechanobiological properties. This has made the design process of materials for bone tissue scaffolds an issue of crucial importance and the object of study of many researchers throughout the world. It is commonly known, in fact, that the rate of bone tissue regeneration and the cellular response is significantly influenced by the scaffold structural response that is, in turn, a function of the scaffold micro-architecture and of the mechanical properties of the material it is made from. The adhesion of stem cells to the scaffold surface as well as the tissue differentiation process occurring in the scaffold pores, are regulated by mechanobiological mechanisms taking place at both the micro- (i.e. some micrometers, approximately the dimension of a stem cell) and macro- (i.e. some hundreds of micrometers, the dimension of scaffold pores) level, respectively. The scaffold surface must be adequately structured to favor the adhesion of stem cells and their consequent differentiation. Similarly, the scaffold architecture must be properly shaped and the scaffold material must be adequately designed to trigger favorable biophysical stimuli, leading to the formation of the bony tissue.

Different studies have recently been published with the aim of better understanding the relationship between the scaffold geometry/material properties and the consequent mechanobiological phenomena taking place inside the scaffold during the regeneration process. However, no clear explanations are yet available on the relationship existing between the mechanical environment and the consequent biological response of tissues occupying the scaffold pores. This Special Issue will gather papers by materials scientists and bone tissue engineers focusing on (but not limited to):

- design techniques to optimize the scaffold performance;

- design of microstructured surfaces to favor the adhesion of stem cells;

- in vitro/in vivo studies aimed to establish relationships between the scaffold structural response and the tissue regeneration process;

- development of innovative biomaterials to fabricate scaffolds for bone tissue engineering;

- optimization of additively manufactured materials to increase scaffold performance;

- computational mechanobiological models simulating the tissue differentiation process in scaffolds.

Dr. Antonio Boccaccio
Guest Editor

Manuscript Submission Information

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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 2000 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

  • Geometry optimization of scaffolds
  • Micro-structured surfaces
  • Cell adhesion
  • Computational mechanobiology
  • Additively manufactured materials

Published Papers (10 papers)

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Research

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Open AccessArticle
In Situ and Ex Situ Designed Hydroxyapatite: Bacterial Cellulose Materials with Biomedical Applications
Materials 2020, 13(21), 4793; https://doi.org/10.3390/ma13214793 - 27 Oct 2020
Cited by 1 | Viewed by 591
Abstract
Hydroxyapatite (HAp) and bacterial cellulose (BC) composite materials represent a promising approach for tissue engineering due to their excellent biocompatibility and bioactivity. This paper presents the synthesis and characterization of two types of materials based on HAp and BC, with antibacterial properties provided [...] Read more.
Hydroxyapatite (HAp) and bacterial cellulose (BC) composite materials represent a promising approach for tissue engineering due to their excellent biocompatibility and bioactivity. This paper presents the synthesis and characterization of two types of materials based on HAp and BC, with antibacterial properties provided by silver nanoparticles (AgNPs). The composite materials were obtained following two routes: (1) HAp was obtained in situ directly in the BC matrix containing different amounts of AgNPs by the coprecipitation method, and (2) HAp was first obtained separately using the coprecipitation method, then combined with BC containing different amounts of AgNPs by ultrasound exposure. The obtained materials were characterized by means of XRD, SEM, and FT-IR, while their antimicrobial effect was evaluated against Gram-negative bacteria (Escherichia coli), Gram-positive bacteria (Staphylococcus aureus), and yeast (Candida albicans). The results demonstrated that the obtained composite materials were characterized by a homogenous porous structure and high water absorption capacity (more than 1000% w/w). These materials also possessed low degradation rates (<5% in simulated body fluid (SBF) at 37 °C) and considerable antimicrobial effect due to silver nanoparticles (10–70 nm) embedded in the polymer matrix. These properties could be finetuned by adjusting the content of AgNPs and the synthesis route. The samples prepared using the in situ route had a wider porosity range and better homogeneity. Full article
(This article belongs to the Special Issue Design of Materials for Bone Tissue Scaffolds)
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Open AccessArticle
Bioengineering Bone Tissue with 3D Printed Scaffolds in the Presence of Oligostilbenes
Materials 2020, 13(20), 4471; https://doi.org/10.3390/ma13204471 - 09 Oct 2020
Cited by 3 | Viewed by 549
Abstract
Diseases determining bone tissue loss have a high impact on people of any age. Bone healing can be improved using a therapeutic approach based on tissue engineering. Scientific research is demonstrating that among bone regeneration techniques, interesting results, in filling of bone lesions [...] Read more.
Diseases determining bone tissue loss have a high impact on people of any age. Bone healing can be improved using a therapeutic approach based on tissue engineering. Scientific research is demonstrating that among bone regeneration techniques, interesting results, in filling of bone lesions and dehiscence have been obtained using adult mesenchymal stem cells (MSCs) integrated with biocompatible scaffolds. The geometry of the scaffold has critical effects on cell adhesion, proliferation and differentiation. Many cytokines and compounds have been demonstrated to be effective in promoting MSCs osteogenic differentiation. Oligostilbenes, such as Resveratrol (Res) and Polydatin (Pol), can increase MSCs osteoblastic features. 3D printing is an excellent technique to create scaffolds customized for the lesion and thus optimized for the patient. In this work we analyze osteoblastic features of adult MSCs integrated with 3D-printed polycarbonate scaffolds differentiated in the presence of oligostilbenes. Full article
(This article belongs to the Special Issue Design of Materials for Bone Tissue Scaffolds)
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Open AccessCommunication
An Algorithm to Optimize the Micro-Geometrical Dimensions of Scaffolds with Spherical Pores
Materials 2020, 13(18), 4062; https://doi.org/10.3390/ma13184062 - 13 Sep 2020
Viewed by 498
Abstract
Despite the wide use of scaffolds with spherical pores in the clinical context, no studies are reported in the literature that optimize the micro-architecture dimensions of such scaffolds to maximize the amounts of neo-formed bone. In this study, a mechanobiology-based optimization algorithm was [...] Read more.
Despite the wide use of scaffolds with spherical pores in the clinical context, no studies are reported in the literature that optimize the micro-architecture dimensions of such scaffolds to maximize the amounts of neo-formed bone. In this study, a mechanobiology-based optimization algorithm was implemented to determine the optimal geometry of scaffolds with spherical pores subjected to both compression and shear loading. We found that these scaffolds are particularly suited to bear shear loads; the amounts of bone predicted to form for this load type are, in fact, larger than those predicted in other scaffold geometries. Knowing the anthropometric characteristics of the patient, one can hypothesize the possible value of load acting on the scaffold that will be implanted and, through the proposed algorithm, determine the optimal dimensions of the scaffold that favor the formation of the largest amounts of bone. The proposed algorithm can guide and support the surgeon in the choice of a “personalized” scaffold that better suits the anthropometric characteristics of the patient, thus allowing to achieve a successful follow-up in the shortest possible time. Full article
(This article belongs to the Special Issue Design of Materials for Bone Tissue Scaffolds)
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Open AccessArticle
Enhanced Osteogenic Differentiation of Human Primary Mesenchymal Stem and Progenitor Cultures on Graphene Oxide/Poly(methyl methacrylate) Composite Scaffolds
Materials 2020, 13(13), 2991; https://doi.org/10.3390/ma13132991 - 05 Jul 2020
Cited by 1 | Viewed by 551
Abstract
Due to its versatility, small size, large surface area, and ability to interact with biological cells and tissues, graphene oxide (GO) is an excellent filler for various polymeric composites and is frequently used to expand their functionality. Even though the major advantage of [...] Read more.
Due to its versatility, small size, large surface area, and ability to interact with biological cells and tissues, graphene oxide (GO) is an excellent filler for various polymeric composites and is frequently used to expand their functionality. Even though the major advantage of the incorporation of GO is the enhancement of mechanical properties of the composite material, GO is also known to improve bioactivity during biomineralization and promote osteoblast adhesion. In this study, we described the fabrication of a composite bone cement made of GO and poly(methyl methacrylate) (PMMA), and we investigated its potential to enhance osteogenic differentiation of human primary mesenchymal stem and progenitor cells. Through the analysis of three differentiation markers, namely alkaline phosphatase, secreted protein acidic and rich in cysteine, and bone morphogenetic protein-2 in the presence and in the absence of an osteogenic differentiation medium, we were able to indicate a composite produced manually with a thick GO paper as the most effective among all investigated samples. This effect was related to its developed surface, possessing a significant number of voids and pores. In this way, GO/PMMA composites were shown as promising materials for the applications in bone tissue engineering. Full article
(This article belongs to the Special Issue Design of Materials for Bone Tissue Scaffolds)
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Open AccessArticle
Evaluation of the Use of an Inorganic Bone Matrix in the Repair of Bone Defects in Rats Submitted to Experimental Alcoholism
Materials 2020, 13(3), 695; https://doi.org/10.3390/ma13030695 - 04 Feb 2020
Cited by 1 | Viewed by 702
Abstract
To assess the effects of chronic alcoholism on the repair of bone defects associated with xenograft. Forty male rats were distributed in: control group (CG, n = 20) and experimental group (EG, n = 20), which received 25% ethanol ad libitum after a [...] Read more.
To assess the effects of chronic alcoholism on the repair of bone defects associated with xenograft. Forty male rats were distributed in: control group (CG, n = 20) and experimental group (EG, n = 20), which received 25% ethanol ad libitum after a period of adaptation. After 90 days of liquid diet, the rats were submitted to 5.0-mm bilateral craniotomy on the parietal bones, subdividing into groups: CCG (control group that received only water with liquid diet and the defect was filled with blood clot), BCG (control group that received only water with liquid diet and the defect was filled with biomaterial), CEG (alcoholic group that received only ethanol solution 25% v/v with liquid diet and the defect was filled with blood clot), and BEG (alcoholic group that received only ethanol solution 25% v/v with liquid diet and the defect was filled with biomaterial). In the analysis of body mass, the drunk animals presented the lowest averages in relation to non-drunk animals during the experimental period. Histomorphologically all groups presented bone formation restricted to the defect margins at 60 days, with bone islets adjacent to the BCG biomaterial particles. CEG showed significant difference compared to BEG only at 40 days (17.42 ± 2.78 vs. 9.59 ± 4.59, respectively). In the birefringence analysis, in early periods all groups showed red-orange birefringence turning greenish-yellow at the end of the experiment. The results provided that, regardless of clinical condition, i.e., alcoholic or non-alcoholic, in the final period of the experiment, the process of bone defect recomposition was similar with the use of xenograft or only clot. Full article
(This article belongs to the Special Issue Design of Materials for Bone Tissue Scaffolds)
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Open AccessFeature PaperArticle
Mechanobiological Approach to Design and Optimize Bone Tissue Scaffolds 3D Printed with Fused Deposition Modeling: A Feasibility Study
Materials 2020, 13(3), 648; https://doi.org/10.3390/ma13030648 - 01 Feb 2020
Cited by 7 | Viewed by 896
Abstract
In spite of the rather large use of the fused deposition modeling (FDM) technique for the fabrication of scaffolds, no studies are reported in the literature that optimize the geometry of such scaffold types based on mechanobiological criteria. We implemented a mechanobiology-based optimization [...] Read more.
In spite of the rather large use of the fused deposition modeling (FDM) technique for the fabrication of scaffolds, no studies are reported in the literature that optimize the geometry of such scaffold types based on mechanobiological criteria. We implemented a mechanobiology-based optimization algorithm to determine the optimal distance between the strands in cylindrical scaffolds subjected to compression. The optimized scaffolds were then 3D printed with the FDM technique and successively measured. We found that the difference between the optimized distances and the average measured ones never exceeded 8.27% of the optimized distance. However, we found that large fabrication errors are made on the filament diameter when the filament diameter to be realized differs significantly with respect to the diameter of the nozzle utilized for the extrusion. This feasibility study demonstrated that the FDM technique is suitable to build accurate scaffold samples only in the cases where the strand diameter is close to the nozzle diameter. Conversely, when a large difference exists, large fabrication errors can be committed on the diameter of the filaments. In general, the scaffolds realized with the FDM technique were predicted to stimulate the formation of amounts of bone smaller than those that can be obtained with other regular beam-based scaffolds. Full article
(This article belongs to the Special Issue Design of Materials for Bone Tissue Scaffolds)
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Open AccessArticle
Lactoferrin-Hydroxyapatite Containing Spongy-Like Hydrogels for Bone Tissue Engineering
Materials 2019, 12(13), 2074; https://doi.org/10.3390/ma12132074 - 27 Jun 2019
Cited by 9 | Viewed by 1226
Abstract
The development of bioactive and cell-responsive materials has fastened the field of bone tissue engineering. Gellan gum (GG) spongy-like hydrogels present high attractive properties for the tissue engineering field, especially due to their wide microarchitecture and tunable mechanical properties, as well as their [...] Read more.
The development of bioactive and cell-responsive materials has fastened the field of bone tissue engineering. Gellan gum (GG) spongy-like hydrogels present high attractive properties for the tissue engineering field, especially due to their wide microarchitecture and tunable mechanical properties, as well as their ability to entrap the responsive cells. Lactoferrin (Lf) and Hydroxyapatite (HAp) are bioactive factors that are known to potentiate faster bone regeneration. Thus, we developed an advanced three-dimensional (3D) biomaterial by integrating these bioactive factors within GG spongy-like hydrogels. Lf-HAp spongy-like hydrogels were characterized in terms of microstructure, water uptake, degradation, and concomitant release of Lf along the time. Human adipose-derived stem cells (hASCs) were seeded and the capacity of these materials to support hASCs in culture for 21 days was assessed. Lf addition within GG spongy-like hydrogels did not change the main features of GG spongy-like hydrogels in terms of porosity, pore size, degradation, and water uptake commitment. Nevertheless, HAp addition promoted an increase of the pore wall thickness (from ~13 to 28 µm) and a decrease on porosity (from ~87% to 64%) and mean pore size (from ~12 to 20 µm), as well as on the degradability and water retention capabilities. A sustained release of Lf was observed for all the formulations up to 30 days. Cell viability assays showed that hASCs were viable during the culture period regarding cell-laden spongy-like hydrogels. Altogether, we demonstrate that GG spongy-like hydrogels containing HAp and Lf in high concentrations gathered favorable 3D bone-like microenvironment with an increased hASCs viability with the presented results. Full article
(This article belongs to the Special Issue Design of Materials for Bone Tissue Scaffolds)
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Open AccessArticle
In Vitro and In Vivo Evaluation of Starfish Bone-Derived β-Tricalcium Phosphate as a Bone Substitute Material
Materials 2019, 12(11), 1881; https://doi.org/10.3390/ma12111881 - 11 Jun 2019
Cited by 3 | Viewed by 1222
Abstract
We evaluated starfish-derived β-tricalcium phosphate (Sf-TCP) obtained by phosphatization of starfish-bone-derived porous calcium carbonate as a potential bone substitute material. The Sf-TCP had a communicating pore structure with a pore size of approximately 10 μm. Although the porosity of Sf-TCP was similar to [...] Read more.
We evaluated starfish-derived β-tricalcium phosphate (Sf-TCP) obtained by phosphatization of starfish-bone-derived porous calcium carbonate as a potential bone substitute material. The Sf-TCP had a communicating pore structure with a pore size of approximately 10 μm. Although the porosity of Sf-TCP was similar to that of Cerasorb M (CM)—a commercially available β-TCP bone filler—the specific surface area was roughly three times larger than that of CM. Observation by scanning electron microscopy showed that pores communicated to the inside of the Sf-TCP. Cell growth tests showed that Sf-TCP improved cell proliferation compared with CM. Cells grown on Sf-TCP showed stretched filopodia and adhered; cells migrated both to the surface and into pores. In vivo, vigorous tissue invasion into pores was observed in Sf-TCP, and more fibrous tissue was observed for Sf-TCP than CM. Moreover, capillary formation into pores was observed for Sf-TCP. Thus, Sf-TCP showed excellent biocompatibility in vitro and more vigorous bone formation in vivo, indicating the possible applications of this material as a bone substitute. In addition, our findings suggested that mimicking the microstructure derived from whole organisms may facilitate the development of superior artificial bone. Full article
(This article belongs to the Special Issue Design of Materials for Bone Tissue Scaffolds)
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Review

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Open AccessReview
Exploring Macroporosity of Additively Manufactured Titanium Metamaterials for Bone Regeneration with Quality by Design: A Systematic Literature Review
Materials 2020, 13(21), 4794; https://doi.org/10.3390/ma13214794 - 27 Oct 2020
Cited by 1 | Viewed by 597
Abstract
Additive manufacturing facilitates the design of porous metal implants with detailed internal architecture. A rationally designed porous structure can provide to biocompatible titanium alloys biomimetic mechanical and biological properties for bone regeneration. However, increased porosity results in decreased material strength. The porosity and [...] Read more.
Additive manufacturing facilitates the design of porous metal implants with detailed internal architecture. A rationally designed porous structure can provide to biocompatible titanium alloys biomimetic mechanical and biological properties for bone regeneration. However, increased porosity results in decreased material strength. The porosity and pore sizes that are ideal for porous implants are still controversial in the literature, complicating the justification of a design decision. Recently, metallic porous biomaterials have been proposed for load-bearing applications beyond surface coatings. This recent science lacks standards, but the Quality by Design (QbD) system can assist the design process in a systematic way. This study used the QbD system to explore the Quality Target Product Profile and Ideal Quality Attributes of additively manufactured titanium porous scaffolds for bone regeneration with a biomimetic approach. For this purpose, a total of 807 experimental results extracted from 50 different studies were benchmarked against proposed target values based on bone properties, governmental regulations, and scientific research relevant to bone implants. The scaffold properties such as unit cell geometry, pore size, porosity, compressive strength, and fatigue strength were studied. The results of this study may help future research to effectively direct the design process under the QbD system. Full article
(This article belongs to the Special Issue Design of Materials for Bone Tissue Scaffolds)
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Other

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Open AccessCase Report
Design Techniques to Optimize the Scaffold Performance: Freeze-dried Bone Custom-made Allografts for Maxillary Alveolar Horizontal Ridge Augmentation
Materials 2020, 13(6), 1393; https://doi.org/10.3390/ma13061393 - 19 Mar 2020
Cited by 4 | Viewed by 846
Abstract
The purpose of the current investigation was to evaluate the clinical success of horizontal ridge augmentation in severely atrophic maxilla (Cawood and Howell class IV) using freeze-dried custom made bone harvested from the tibial hemiplateau of cadaver donors, and to analyze the marginal [...] Read more.
The purpose of the current investigation was to evaluate the clinical success of horizontal ridge augmentation in severely atrophic maxilla (Cawood and Howell class IV) using freeze-dried custom made bone harvested from the tibial hemiplateau of cadaver donors, and to analyze the marginal bone level gain prior to dental implant placement at nine months subsequent to bone grafting and before prosthetic rehabilitation. A 52-year-old woman received custom made bone grafts. The patient underwent CT scans two weeks prior and nine months after surgery for graft volume and density analysis. The clinical and radiographic bone observations showed a very low rate of resorption after bone graft and implant placement. The custom-made allograft material was a highly effective modality for restoring the alveolar horizontal ridge, resulting in a reduction of the need to obtain autogenous bone from a secondary site with predictable procedure. Further studies are needed to investigate its behavior at longer time periods. Full article
(This article belongs to the Special Issue Design of Materials for Bone Tissue Scaffolds)
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Planned Papers

The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.

1. Lactoferrin-Hydroxyapatite Containing Spongy-like Hydrogels for Bone Tissue Engineering

Ana Raquel Bastos1,2, Lucília Pereira da Silva1,2, Fátima Raquel Maia1,2,3, Tânia Rodrigues1,2, Filipa Sousa1,2, Joaquim Miguel Oliveira1,2,3, Jillian Cornish4, Vitor Manuel Correlo1,2,3 and Rui Luís Reis1,2,3

13B's Research Group, I3Bs – Research Institute on Biomaterials, Biodegradables and Biomimetics,  University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ciência e Tecnologia, Zona Industrial da Gandra, 4805-017 Barco, Guimarães, Portugal;

2ICVS/3B’s - PT Government Associated Laboratory, Portugal;

3The Discoveries Centre for Regenerative and Precision Medicine, Headquarters at University of Minho, Avepark, 4805-017 Barco, Guimarães, Portugal;

4Department of Medicine, University of Auckland, Auckland, New Zealand

2. Novel titanium-based scaffolds in bone regeneration: types and application

Maja Antunovic, Maja Pusić, Slaven Babic, Katarina Caput Mihalic and Inga Marijanovic *.

Department of Biology, Faculty of Science, University of Zagreb; Traumatology Clinic, Clinical Hospital Centre “Sestre Milosrdnice”, Zagreb.

Title: Chemical composition and particle size of synthetic ceramics delivered with rhBMP6 in autologous blood coagulum determine the ectopic bone structure in a rat one year follow up study
Authors: Nikola Stokovic1,2; Natalia Ivanjko1,2; Marina Milesevic1,2,; Igor Erjavec1,2; T Kuber Sampath3; Slobodan Vukicevic1,2
Affiliation: 1 Laboratory for Mineralized Tissues, University of Zagreb School of Medicine, Zagreb, Croatia 2 Scientific Center of Excellence for Reproductive and Regenerative Medicine 3 perForm Biologics Inc, Holliston, Massachusetts, USA

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