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Patient-Tailored Biomimetic Scaffold Constructs for Bone Regeneration
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Patient-Tailored Biomimetic Scaffold Constructs for Bone Regeneration

A special issue of Applied Sciences (ISSN 2076-3417). This special issue belongs to the section "Materials Science and Engineering".

Deadline for manuscript submissions: closed (31 January 2021) | Viewed by 30416

Special Issue Editors

Dr. Wanda Lattanzi

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Guest Editor
1. Dipartimento Scienze della Vita e Sanità Pubblica, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
2. Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
Interests: bone biology; osteogenic mechanisms; bone regenerative strategies; orthopedics; craniofacial surgery
Special Issues, Collections and Topics in MDPI journals
Dr. Alessandro Arcovito

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Guest Editor
1. Dipartimento di Scienze Biotecnologiche di Base Cliniche Intensivologiche e Perioperatorie, Sezione di Biochimica, Università Cattolica del Sacro Cuore, 29010 Rome, Italy
2. Fondazione Policlinico Universitario A. Gemelli—IRCCS, 00168 Rome, Italy
Interests: drug design; drug delivery; protein interactions
Special Issues, Collections and Topics in MDPI journals
Dr. Giuseppina Nocca

E-Mail Website
Guest Editor
1. Dipartimento di Scienze Biotecnologiche di Base, Cliniche Intensivologiche e Perioperatorie, Sezione di Biochimica, Università Cattolica del Sacro Cuore, Roma, Italy
2. Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy
Interests: cell–material interactions; drug delivery; biological characterization of nano- and micromaterials
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Ilaria Cacciotti

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Guest Editor
Department of Engineering, INSTM RU, University of Rome “Niccolò Cusano”, Via Don Carlo Gnocchi 3, 00166 Roma, Italy
Interests: biomaterials; bioceramics; biopolymers; biocomposites; ecosustainable materials; scaffold; spheres; fibers; coatings; sol–gel processes; valorization of agro-food waste extracts and by-products; electrospinning; additive manufacturing; physicochemical characterization; microstructure; thermal and mechanical properties; tissue engineering/regenerative medicine; drug delivery
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The present-day health demographic scenario shows an increasingly aging population. Age-related bone frailty represents a critical medical challenge in particular, owing to the physiologic decrease in bone self-healing properties and the heterogeneous co-morbidities that coexist in the elderly. The incidence of fragility fractures in Europe was nearly 3 million in 2017 and is foreseen to increase significantly in the next few decades, creating a pressing need for rapid technological improvement in the field of bone reconstructive/regenerative techniques. Native bone tissue features a complex three-dimensional structure, with multiple levels of complexity, from the molecular, through the nanostructure to the micro- and macroscopic architecture. To achieve an effective restoration of tissue morphology and functionality, new biomimetic systems and bone tissue engineering strategies are emerging, as an alternative to bone grafting and conventional static scaffold compounds, to achieve the dynamic changes needed for the correct balance between mechanical strength and plasticity in the newly formed bone. Implants for tissue engineering strongly depend on (bio)materials, on the manufacturing process, and on the possible implementation of biological structures, including stem cells, growth factors, and derivatives. In this context, the rapid advance in additive manufacturing techniques offers a promising tool, particularly in the vision of a custom-made, patient-oriented approach. However, it is still necessary to better identify and overcome technical and regulatory drawbacks.

This Special Issue aims to address the challenges in the development of new biomimetic systems and technologies in the field of bone regeneration and reconstruction, including new scaffold design and engineering novel biomaterials, innovative scaffold design, advanced (bio)printing and 4D printing techniques, scaffold–cell interactions, drug delivery and scaffold functionalization strategies, imaging techniques for ultrastructural characterization, and valuable state-of-the art meta-analyses, in order to provide a complete and multidisciplinary vision of the faced thematic, from the engineering aspect to the biological and clinical point of view.

Prof. Dr. Wanda Lattanzi
Prof. Dr. Alessandro Arcovito
Prof. Dr. Giuseppina Nocca
Prof. Dr. Ilaria Cacciotti
Guest Editors

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Keywords

  • osteoconduction
  • osteoinduction
  • biomimetic scaffolds
  • personalized medicine
  • additive manufacturing
  • biotechnology
  • nanotechnology
  • regenerative medicine

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Published Papers (6 papers)

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Research

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22 pages, 9681 KiB  
Article
Robocasting of Single and Multi-Functional Calcium Phosphate Scaffolds and Its Hybridization with Conventional Techniques: Design, Fabrication and Characterization
by Mehdi Mohammadi, Patricia Pascaud-Mathieu, Valeria Allizond, Jean-Marc Tulliani, Bartolomeo Coppola, Giuliana Banche, Christophe Chaput, Anna Maria Cuffini, Fabrice Rossignol and Paola Palmero
Appl. Sci. 2020, 10(23), 8677; https://doi.org/10.3390/app10238677 - 4 Dec 2020
Cited by 20 | Viewed by 2799
Abstract
In this work, dense, porous, and, for the first time, functionally-graded bi-layer scaffolds with a cylindrical geometry were produced from a commercially available hydroxyapatite powder using the robocasting technique. The bi-layer scaffolds were made of a dense core part attached to a surrounding [...] Read more.
In this work, dense, porous, and, for the first time, functionally-graded bi-layer scaffolds with a cylindrical geometry were produced from a commercially available hydroxyapatite powder using the robocasting technique. The bi-layer scaffolds were made of a dense core part attached to a surrounding porous part. Subsequently, these bi-layer robocast scaffolds were joined with an outer shell of an antibacterial porous polymer layer fabricated by solvent casting/salt leaching techniques, leading to hybrid ceramic-polymer scaffolds. The antibacterial functionality was achieved through the addition of silver ions to the polymer layer. All the robocast samples, including the bi-layer ones, were first characterized through scanning electron microscopy observations, mechanical characterization in compression and preliminary bioactivity tests. Then, the hybrid bi-layer ceramic-polymer scaffolds were characterized through antimicrobial tests. After sintering at 1300 °C for 3 h, the compressive strengths of the structures were found to be equal to 29 ± 4 MPa for dense samples and 7 ± 4 MPa for lattice structures with a porosity of 34.1%. Bioactivity tests performed at 37 °C for 4 weeks showed that the precipitated layer on the robocast samples contained octacalcium phosphate. Finally, it was evidenced that the hybrid structure was effective in releasing antibacterial Ag+ ions to the surrounding medium showing its potential efficiency in limiting Staphylococcus aureus proliferation during surgery. Full article
(This article belongs to the Special Issue Patient-Tailored Biomimetic Scaffold Constructs for Bone Regeneration)
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15 pages, 1573 KiB  
Article
Sintering Behavior of a Six-Oxide Silicate Bioactive Glass for Scaffold Manufacturing
by Elisa Fiume, Gianpaolo Serino, Cristina Bignardi, Enrica Verné and Francesco Baino
Appl. Sci. 2020, 10(22), 8279; https://doi.org/10.3390/app10228279 - 22 Nov 2020
Cited by 12 | Viewed by 2291
Abstract
The intrinsic brittleness of bioactive glasses (BGs) is one of the main barriers to the widespread use of three-dimensional porous BG-derived bone grafts (scaffolds) in clinical practice. Among all the available strategies for improving the mechanical properties of BG-based scaffolds, strut densification upon [...] Read more.
The intrinsic brittleness of bioactive glasses (BGs) is one of the main barriers to the widespread use of three-dimensional porous BG-derived bone grafts (scaffolds) in clinical practice. Among all the available strategies for improving the mechanical properties of BG-based scaffolds, strut densification upon sintering treatments at high temperatures represents a relatively easy approach, but its implementation might lead to undesired and poorly predictable decrease in porosity, mass transport properties and bioactivity resulting from densification and devitrification phenomena occurring in the material upon heating. The aim of the present work was to investigate the sinter-crystallization of a highly bioactive SiO2-P2O5-CaO–MgO–Na2O–K2O glass (47.5B composition) in reference to its suitability for the fabrication of bonelike foams. The thermal behavior of 47.5B glass particles was investigated upon sintering at different temperatures in the range of 600–850 °C by means of combined thermal analyses (differential thermal analysis (DTA) and hot-stage microscopy (HSM)). Then, XRD measurements were carried out to identify crystalline phases developed upon sintering. Finally, porous scaffolds were produced by a foam replica method in order to evaluate the effect of the sintering temperature on the mechanical properties under compression loading conditions. Assessing a relationship between mechanical properties and sintering temperature, or in other words between scaffold performance and fabrication process, is a key step towards the rationale design of optimized scaffolds for tissue repair. Full article
(This article belongs to the Special Issue Patient-Tailored Biomimetic Scaffold Constructs for Bone Regeneration)
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15 pages, 1316 KiB  
Article
Evaluation of Aloe Vera Coated Polylactic Acid Scaffolds for Bone Tissue Engineering
by Ricardo Donate, María Elena Alemán-Domínguez, Mario Monzón, Jianshu Yu, Francisco Rodríguez-Esparragón and Chaozong Liu
Appl. Sci. 2020, 10(7), 2576; https://doi.org/10.3390/app10072576 - 9 Apr 2020
Cited by 11 | Viewed by 3772
Abstract
3D-printed polylactic acid (PLA) scaffolds have been demonstrated as being a promising tool for the development of tissue-engineered replacements of bone. However, this material lacks a suitable surface chemistry to efficiently interact with extracellular proteins and, consequently, to integrate into the surrounding tissue [...] Read more.
3D-printed polylactic acid (PLA) scaffolds have been demonstrated as being a promising tool for the development of tissue-engineered replacements of bone. However, this material lacks a suitable surface chemistry to efficiently interact with extracellular proteins and, consequently, to integrate into the surrounding tissue when implanted in vivo. In this study, aloe vera coatings have been proposed as a strategy to improve the bioaffinity of this type of structures. Aloe vera coatings were applied at three different values of pH (3, 4 and 5), after treating the surface of the PLA scaffolds with oxygen plasma. The surface modification of the material has been assessed through X-ray photoelectron spectroscopy (XPS) analysis and water contact angle measurements. In addition, the evaluation of the enzymatic degradation of the structures showed that the pH of the aloe vera extracts used as coating influences the degradation rate of the PLA-based scaffolds. Finally, the cell metabolic activity of an in vitro culture of human fetal osteoblastic cells on the samples revealed an improvement of this parameter on aloe vera coated samples, especially for those treated at pH 3. Hence, these structures showed potential for being applied for bone tissue regeneration. Full article
(This article belongs to the Special Issue Patient-Tailored Biomimetic Scaffold Constructs for Bone Regeneration)
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12 pages, 2364 KiB  
Article
The Synergic Effect of Terpenoid and Steroidal Saponins Can Improve Bone Healing, by Promoting the Osteogenic Commitment of Adipose Mesenchymal Stem Cells: An In Vitro Study
by Gloria Bellin, Chiara Gardin, Letizia Ferroni, Paolo Ghensi, Barbara Zavan and Marco Tatullo
Appl. Sci. 2019, 9(16), 3426; https://doi.org/10.3390/app9163426 - 20 Aug 2019
Cited by 1 | Viewed by 4279
Abstract
Bone regeneration involves several biological processes that consistently impact the quality of tissue healing. An important step consists of the local recruitment and differentiation of mesenchymal stem cells that migrate in the site to regenerate from bone marrow. Mesenchymal stem cells (MSCs) may [...] Read more.
Bone regeneration involves several biological processes that consistently impact the quality of tissue healing. An important step consists of the local recruitment and differentiation of mesenchymal stem cells that migrate in the site to regenerate from bone marrow. Mesenchymal stem cells (MSCs) may be pushed towards osteogenic commitment by specific substances, often naturally present in plants. Yunnan Baiyao (YB) is a Chinese herbal medicine, mainly working through the synergic effect of terpenoid and steroidal saponins. YB is well known for its numerous biomedical effects, including the ability to favor improved bone tissue healing. In our in vitro study, we used adipose mesenchymal stem cells (ADSCs) as a study-model: We selected samples to harvest and isolate ADSCs and investigate their viability; moreover, we performed bone-related gene expression to evaluate the differentiation of MSCs. To confirm this behavior, we analyzed alkaline phosphate activity and calcium deposition, with ADSCs cultured in basal and osteogenic media, with YB at different concentrations in the medium, and at different time-points: 7, 14 and 21 days. Our results indicate that the synergic effect of terpenoid and steroidal saponins slightly favor the late ADSCs differentiation towards the osteoblasts phenotype. In osteogenic committed cells, the treatment with the lower dose of YB promoted the up-regulation of the alkaline phosphatase gene (ALPL) at day seven and 14 (p < 0.01); at day 21, the alkaline phosphatase (ALP) activity showed a slight increase, although in basal condition it maintains low rates. We assume that such molecular synergy can promote the osteogenic commitment of adipose mesenchymal stem cells, thus improving the timing and the quality of bone healing. Full article
(This article belongs to the Special Issue Patient-Tailored Biomimetic Scaffold Constructs for Bone Regeneration)
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Review

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35 pages, 1152 KiB  
Review
Personalized Bone Reconstruction and Regeneration in the Treatment of Craniosynostosis
by Federica Tiberio, Ilaria Cacciotti, Paolo Frassanito, Giuseppina Nocca, Gianpiero Tamburrini, Alessandro Arcovito and Wanda Lattanzi
Appl. Sci. 2021, 11(6), 2649; https://doi.org/10.3390/app11062649 - 16 Mar 2021
Cited by 6 | Viewed by 7153
Abstract
Craniosynostosis (CS) is the second most prevalent craniofacial congenital malformation due to the premature fusion of skull sutures. CS care requires surgical treatment of variable complexity, aimed at resolving functional and cosmetic defects resulting from the skull growth constrain. Despite significant innovation in [...] Read more.
Craniosynostosis (CS) is the second most prevalent craniofacial congenital malformation due to the premature fusion of skull sutures. CS care requires surgical treatment of variable complexity, aimed at resolving functional and cosmetic defects resulting from the skull growth constrain. Despite significant innovation in the management of CS, morbidity and mortality still exist. Residual cranial defects represent a potential complication and needdedicated management to drive a targeted bone regeneration while modulating suture ossification. To this aim, existing techniques are rapidly evolving and include the implementation of novel biomaterials, 3D printing and additive manufacturing techniques, and advanced therapies based on tissue engineering. This review aims at providing an exhaustive and up-to-date overview of the strategies in use to correct these congenital defects, focusing on the technological advances in the fields of biomaterials and tissue engineering implemented in pediatric surgical skull reconstruction, i.e., biodegradable bone fixation systems, biomimetic scaffolds, drug delivery systems, and cell-based approaches. Full article
(This article belongs to the Special Issue Patient-Tailored Biomimetic Scaffold Constructs for Bone Regeneration)
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11 pages, 664 KiB  
Review
The Impact of Optogenetics on Regenerative Medicine
by Gianrico Spagnuolo, Fabio Genovese, Leonzio Fortunato, Michele Simeone, Carlo Rengo and Marco Tatullo
Appl. Sci. 2020, 10(1), 173; https://doi.org/10.3390/app10010173 - 24 Dec 2019
Cited by 9 | Viewed by 8951
Abstract
Optogenetics is a novel strategic field that combines light (opto-) and genetics (genetic) into applications able to control the activity of excitable cells and neuronal circuits. Using genetic manipulation, optogenetics may induce the coding of photosensitive ion channels on specific neurons: this non-invasive [...] Read more.
Optogenetics is a novel strategic field that combines light (opto-) and genetics (genetic) into applications able to control the activity of excitable cells and neuronal circuits. Using genetic manipulation, optogenetics may induce the coding of photosensitive ion channels on specific neurons: this non-invasive technology combines several approaches that allow users to achieve improved optical control and higher resolution. This technology can be applied to optical systems already present in the clinical-diagnostic field, and it has also excellent effects on biological investigations and on therapeutic strategies. Recently, several biomedical applications of optogenetics have been investigated, such as applications in ophthalmology, in bone repairing, in heart failure recovery, in post-stroke recovery, in tissue engineering, and regenerative medicine (TERM). Nevertheless, the most promising and developed applications of optogenetics are related to dynamic signal coding in cell physiology and neurological diseases. In this review, we will describe the state of the art and future insights on the impact of optogenetics on regenerative medicine. Full article
(This article belongs to the Special Issue Patient-Tailored Biomimetic Scaffold Constructs for Bone Regeneration)
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