Multidisciplinary Insights on Bone Healing (Volume II)

A special issue of Biology (ISSN 2079-7737).

Deadline for manuscript submissions: 15 April 2024 | Viewed by 14737

Special Issue Editors

Department of Medical and Surgical Sciences for Children & Adults, Università degli Studi di Modena e Reggio Emilia, Via del Pozzo 71, 41124 Modena, Italy
Interests: bioceramics based bone grafting materials for regenerative biomedicine; bioceramics biocompatibility through in vitro/cytotoxicity assays, and /in vivo /implantation in animal model; bone cutting device evaluation, both for rotatory instruments and piezosurgical osteotomes; microsurgical flap reconstruction for head & neck defects; deep learning and computing technology in maxillo-facial surgery, head & neck surgical oncology
Special Issues, Collections and Topics in MDPI journals
Unit of Dentistry and Maxillo-Facial Surgery, Surgery, Dentistry, Maternity and Infant Department, University of Verona, P.le L.A. Scuro 10, 37134 Verona, Italy
Interests: bioceramics based bone grafting materials for regenerative biomedicine; bioceramics biocompatibility through in vitro/cytotoxicity assays, and /in vivo /implantation in animal model; bone cutting device evaluation, both for rotatory instruments and piezosurgical osteotomes; microsurgical flap reconstruction for head & neck defects; deep learning and the use of new technologies in maxillo-facial surgery; head & neck surgical oncology; pediatric diseases of the cervico-facial district

Special Issue Information

Dear Colleagues,

At the basis of the bone healing process there is a sophisticated multifactorial “system” composed of both macro- and microscopic agents that interact each other in order to obtain the recovery of correct morphological and functional features. Bone tissue-specific agents and extra-bone factors can influence the final outcome at several levels; all of them are characterized by complex and multidisciplinary perspectives that have raised many questions that have yet to be fully elucidated. The development of new technologies has improved the methodology to evaluate the findings. The consequence has been the raising of the curtain on this fascinating topic, which must be looked at from different angles in order to be correctly framed.

Basic research with a translational approach concerning the bone healing process is a growing field of study. Interdisciplinarity between pre-clinical (e.g., the interaction of tissue and biophysical energy), medical (e.g., innovative pharmacological protocols) and surgical specialties, as well as regenerative medicine strategies, may result in a common enrichment in terms of the knowledge of bone healing processes and a perspective in applying these notions for the safety of patients. We hope that researchers with different areas of expertise will consider contributing to this Special Issue.

Dr. Alexandre Anesi
Dr. Mattia Di Bartolomeo
Guest Editors

Manuscript Submission Information

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Keywords

  • bone healing
  • bone regeneration
  • bone diseases and related pathologies
  • bone tissue engineering
  • bone substitute

Related Special Issue

Published Papers (8 papers)

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Research

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17 pages, 27588 KiB  
Article
Multipotent Mesenchymal Cells Homing and Differentiation on Poly(ε-caprolactone) Blended with 20% Tricalcium Phosphate and Polylactic Acid Incorporating 10% Hydroxyapatite 3D-Printed Scaffolds via a Commercial Fused Deposition Modeling 3D Device
by Nicola De Angelis, Andrea Amaroli, Alberto Lagazzo, Fabrizio Barberis, Pier Raffaele Zarro, Alessia Cappelli, Maria Giovanna Sabbieti and Dimitrios Agas
Biology 2023, 12(12), 1474; https://doi.org/10.3390/biology12121474 - 28 Nov 2023
Cited by 2 | Viewed by 1323
Abstract
As highlighted by the ‘Global Burden of Disease Study 2019’ conducted by the World Health Organization, ensuring fair access to medical care through affordable and targeted treatments remains crucial for an ethical global healthcare system. Given the escalating demand for advanced and urgently [...] Read more.
As highlighted by the ‘Global Burden of Disease Study 2019’ conducted by the World Health Organization, ensuring fair access to medical care through affordable and targeted treatments remains crucial for an ethical global healthcare system. Given the escalating demand for advanced and urgently needed solutions in regenerative bone procedures, the critical role of biopolymers emerges as a paramount necessity, offering a groundbreaking avenue to address pressing medical needs and revolutionize the landscape of bone regeneration therapies. Polymers emerge as excellent solutions due to their versatility, making them reliable materials for 3D printing. The development and widespread adoption of this technology would impact production costs and enhance access to related healthcare services. For instance, in dentistry, the use of commercial polymers blended with β-tricalcium phosphate (TCP) is driven by the need to print a standardized product with osteoconductive features. However, modernization is required to bridge the gap between biomaterial innovation and the ability to print them through commercial printing devices. Here we showed, for the first time, the metabolic behavior and the lineage commitment of bone marrow-derived multipotent mesenchymal cells (MSCs) on the 3D-printed substrates poly(e-caprolactone) combined with 20% tricalcium phosphate (PCL + 20% β-TCP) and L-polylactic acid (PLLA) combined with 10% hydroxyapatite (PLLA + 10% HA). Although there are limitations in printing additive-enriched polymers with a predictable and short half-life, the tested 3D-printed biomaterials were highly efficient in supporting osteoinductivity. Indeed, considering different temporal sequences, both 3D-printed biomaterials resulted as optimal scaffolds for MSCs’ commitment toward mature bone cells. Of interest, PLLA + 10% HA substrates hold the confirmation as the finest material for osteoinduction of MSCs. Full article
(This article belongs to the Special Issue Multidisciplinary Insights on Bone Healing (Volume II))
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16 pages, 5686 KiB  
Article
Identifying Fibroblast Growth Factor Receptor 3 as a Mediator of Periosteal Osteochondral Differentiation through the Construction of microRNA-Based Interaction Networks
by Leah M. Wells, Helen C. Roberts, Frank P. Luyten and Scott J. Roberts
Biology 2023, 12(11), 1381; https://doi.org/10.3390/biology12111381 - 28 Oct 2023
Viewed by 1048
Abstract
Human periosteum-derived progenitor cells (hPDCs) have the ability to differentiate towards both the chondrogenic and osteogenic lineages. This coordinated and complex osteochondrogenic differentiation process permits endochondral ossification and is essential in bone development and repair. We have previously shown that humanised cultures of [...] Read more.
Human periosteum-derived progenitor cells (hPDCs) have the ability to differentiate towards both the chondrogenic and osteogenic lineages. This coordinated and complex osteochondrogenic differentiation process permits endochondral ossification and is essential in bone development and repair. We have previously shown that humanised cultures of hPDCs enhance their osteochondrogenic potentials in vitro and in vivo; however, the underlying mechanisms are largely unknown. This study aimed to identify novel regulators of hPDC osteochondrogenic differentiation through the construction of miRNA-mRNA regulatory networks derived from hPDCs cultured in human serum or foetal bovine serum as an alternative in silico strategy to serum characterisation. Sixteen differentially expressed miRNAs (DEMis) were identified in the humanised culture. In silico analysis of the DEMis with TargetScan allowed for the identification of 1503 potential miRNA target genes. Upon comparison with a paired RNAseq dataset, a 4.5% overlap was observed (122 genes). A protein–protein interaction network created with STRING interestingly identified FGFR3 as a key network node, which was further predicted using multiple pathway analyses. Functional analysis revealed that hPDCs with the activating mutation FGFR3N540K displayed increased expressions of chondrogenic gene markers when cultured under chondrogenic conditions in vitro and displayed enhanced endochondral bone formation in vivo. A further histological analysis uncovered known downstream mediators involved in FGFR3 signalling and endochondral ossification to be upregulated in hPDC FGFR3N540K-seeded implants. This combinational approach of miRNA-mRNA-protein network analysis with in vitro and in vivo characterisation has permitted the identification of FGFR3 as a novel mediator of hPDC biology. Furthermore, this miRNA-based workflow may also allow for the identification of drug targets, which may be of relevance in instances of delayed fracture repair. Full article
(This article belongs to the Special Issue Multidisciplinary Insights on Bone Healing (Volume II))
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18 pages, 1651 KiB  
Article
The Capacity of Magnesium to Induce Osteoclast Differentiation Is Greatly Enhanced by the Presence of Zoledronate
by Silvia Ricchiuto, Rossella Palumbo, Francesca Lami, Francesca Gavioli, Lorenzo Caselli, Monica Montanari, Vincenzo Zappavigna, Alexandre Anesi, Tommaso Zanocco-Marani and Alexis Grande
Biology 2023, 12(10), 1297; https://doi.org/10.3390/biology12101297 - 29 Sep 2023
Viewed by 921
Abstract
Bisphosphonates (BPs) are successfully used to cure a number of diseases characterized by a metabolic reduction in bone density, such as Osteoporosis, or a neoplastic destruction of bone tissue, such as multiple myeloma and bone metastases. These drugs exert their therapeutic effect by [...] Read more.
Bisphosphonates (BPs) are successfully used to cure a number of diseases characterized by a metabolic reduction in bone density, such as Osteoporosis, or a neoplastic destruction of bone tissue, such as multiple myeloma and bone metastases. These drugs exert their therapeutic effect by causing a systemic osteoclast depletion that, in turn, is responsible for reduced bone resorption. Unfortunately, in addition to their beneficial activity, BPs can also determine a frightening side effect known as osteonecrosis of the jaw (ONJ). It is generally believed that the inability of osteoclasts to dispose of inflamed/necrotic bone represents the main physiopathological aspect of ONJ. In principle, a therapeutic strategy able to elicit a local re-activation of osteoclast production could counteract ONJ and promote the healing of its lesions. Using an experimental model of Vitamin D3-dependent osteoclastogenesis, we have previously demonstrated that Magnesium is a powerful inducer of osteoclast differentiation. Here we show that, surprisingly, this effect is greatly enhanced by the presence of Zoledronate, chosen for our study because it is the most effective and dangerous of the BPs. This finding allows us to hypothesize that Magnesium might play an important role in the topical therapy of ONJ. Full article
(This article belongs to the Special Issue Multidisciplinary Insights on Bone Healing (Volume II))
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15 pages, 3167 KiB  
Article
Tackling Inequalities in Oral Health: Bone Augmentation in Dental Surgery through the 3D Printing of Poly(ε-caprolactone) Combined with 20% Tricalcium Phosphate
by Nicola De Angelis, Andrea Amaroli, Maria Giovanna Sabbieti, Alessia Cappelli, Alberto Lagazzo, Claudio Pasquale, Fabrizio Barberis and Dimitrios Agas
Biology 2023, 12(4), 536; https://doi.org/10.3390/biology12040536 - 31 Mar 2023
Cited by 2 | Viewed by 1313
Abstract
The concept of personalized medicine and overcoming healthcare inequalities have become extremely popular in recent decades. Polymers can support cost reductions, the simplicity of customized printing processes, and possible future wide-scale expansion. Polymers with β-tricalcium phosphate (TCP) are well known for their synergy [...] Read more.
The concept of personalized medicine and overcoming healthcare inequalities have become extremely popular in recent decades. Polymers can support cost reductions, the simplicity of customized printing processes, and possible future wide-scale expansion. Polymers with β-tricalcium phosphate (TCP) are well known for their synergy with oral tissues and their ability to induce osteoconductivity. However, poor information exists concerning their properties after the printing process and whether they can maintain an unaffected biological role. Poly(ε-caprolactone) (PCL) polymer and PCL compounded with TCP 20% composite were printed with a Prusa Mini-LCD-®3D printer. Samples were sterilised by immersion in a 2% peracetic acid solution. Sample analyses were performed using infrared-spectroscopy and statical mechanical tests. Biocompatibility tests, such as cell adhesion on the substrate, evaluations of the metabolic activity of viable cells on substrates, and F-actin labelling, followed by FilaQuant-Software were performed using a MC3T3-E1 pre-osteoblasts line. PCL+β-TCP-20% composite is satisfactory for commercial 3D printing and appears suitable to sustain an ISO14937:200937 sterilization procedure. In addition, the proper actin cytoskeleton rearrangement clearly shows their biocompatibility as well as their ability to favour osteoblast adhesion, which is a pivotal condition for cell proliferation and differentiation. Full article
(This article belongs to the Special Issue Multidisciplinary Insights on Bone Healing (Volume II))
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Review

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13 pages, 295 KiB  
Review
Bone Disorders in Pediatric Chronic Kidney Disease: A Literature Review
by Lavinia Capossela, Serena Ferretti, Silvia D’Alonzo, Lorenzo Di Sarno, Valeria Pansini, Antonietta Curatola, Antonio Chiaretti and Antonio Gatto
Biology 2023, 12(11), 1395; https://doi.org/10.3390/biology12111395 - 02 Nov 2023
Cited by 1 | Viewed by 1483
Abstract
Intense changes in mineral and bone metabolism are frequent in chronic kidney disease (CKD) and represent an important cause of morbidity and reduced quality of life. These disorders have conventionally been defined as renal osteodystrophy and classified based on bone biopsy, but due [...] Read more.
Intense changes in mineral and bone metabolism are frequent in chronic kidney disease (CKD) and represent an important cause of morbidity and reduced quality of life. These disorders have conventionally been defined as renal osteodystrophy and classified based on bone biopsy, but due to a lack of bone biopsy data and validated radiological methods to evaluate bone morphology in children, it has been challenging to effectively assess renal osteodystrophy in pediatric CKD; the consequence has been the suboptimal management of bone disorders in children. CKD–mineral and bone disorder (CKD-MBD) is a new expression used to describe a systemic disorder of mineral and bone metabolism as a result of CKD. CKD-MBD is a triad of biochemical imbalances in calcium, phosphate, parathyroid hormone, and vitamin D; bone deformities and soft tissue calcification. This literature review aims to explore the pathogenesis, diagnostic approach, and treatment of CKD-MBD in children and the effects of renal osteodystrophy on growing skeleton, with a specific focus on the biological basis of this peculiar condition. Full article
(This article belongs to the Special Issue Multidisciplinary Insights on Bone Healing (Volume II))
32 pages, 1140 KiB  
Review
Bone Involvement in Rheumatoid Arthritis and Spondyloartritis: An Updated Review
by Francesco Orsini, Chiara Crotti, Gilberto Cincinelli, Raffaele Di Taranto, Andrea Amati, Matteo Ferrito, Massimo Varenna and Roberto Caporali
Biology 2023, 12(10), 1320; https://doi.org/10.3390/biology12101320 - 09 Oct 2023
Viewed by 1283
Abstract
Several rheumatologic diseases are primarily distinguished by their involvement of bone tissue, which not only serves as a mere target of the condition but often plays a pivotal role in its pathogenesis. This scenario is particularly prominent in chronic inflammatory arthritis such as [...] Read more.
Several rheumatologic diseases are primarily distinguished by their involvement of bone tissue, which not only serves as a mere target of the condition but often plays a pivotal role in its pathogenesis. This scenario is particularly prominent in chronic inflammatory arthritis such as rheumatoid arthritis (RA) and spondyloarthritis (SpA). Given the immunological and systemic nature of these diseases, in this review, we report an overview of the pathogenic mechanisms underlying specific bone involvement, focusing on the complex interactions that occur between bone tissue’s own cells and the molecular and cellular actors of the immune system, a recent and fascinating field of interest defined as osteoimmunology. Specifically, we comprehensively elaborate on the distinct pathogenic mechanisms of bone erosion seen in both rheumatoid arthritis and spondyloarthritis, as well as the characteristic process of aberrant bone formation observed in spondyloarthritis. Lastly, chronic inflammatory arthritis leads to systemic bone involvement, resulting in systemic bone loss and consequent osteoporosis, along with increased skeletal fragility. Full article
(This article belongs to the Special Issue Multidisciplinary Insights on Bone Healing (Volume II))
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18 pages, 3852 KiB  
Review
CAM Model: Intriguing Natural Bioreactor for Sustainable Research and Reliable/Versatile Testing
by Carla Palumbo, Federica Sisi and Marta Checchi
Biology 2023, 12(9), 1219; https://doi.org/10.3390/biology12091219 - 08 Sep 2023
Viewed by 1282
Abstract
We are witnessing the revival of the CAM model, which has already used been in the past by several researchers studying angiogenesis and anti-cancer drugs and now offers a refined model to fill, in the translational meaning, the gap between in vitro and [...] Read more.
We are witnessing the revival of the CAM model, which has already used been in the past by several researchers studying angiogenesis and anti-cancer drugs and now offers a refined model to fill, in the translational meaning, the gap between in vitro and in vivo studies. It can be used for a wide range of purposes, from testing cytotoxicity, pharmacokinetics, tumorigenesis, and invasion to the action mechanisms of molecules and validation of new materials from tissue engineering research. The CAM model is easy to use, with a fast outcome, and makes experimental research more sustainable since it allows us to replace, reduce, and refine pre-clinical experimentation (“3Rs” rules). This review aims to highlight some unique potential that the CAM-assay presents; in particular, the authors intend to use the CAM model in the future to verify, in a microenvironment comparable to in vivo conditions, albeit simplified, the angiogenic ability of functionalized 3D constructs to be used in regenerative medicine strategies in the recovery of skeletal injuries of critical size (CSD) that do not repair spontaneously. For this purpose, organotypic cultures will be planned on several CAMs set up in temporal sequences, and a sort of organ model for assessing CSD will be utilized in the CAM bioreactor rather than in vivo. Full article
(This article belongs to the Special Issue Multidisciplinary Insights on Bone Healing (Volume II))
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12 pages, 1222 KiB  
Review
The Role of Sex Differences in Bone Health and Healing
by Elena Ortona, Maria Teresa Pagano, Lavinia Capossela and Walter Malorni
Biology 2023, 12(7), 993; https://doi.org/10.3390/biology12070993 - 12 Jul 2023
Cited by 4 | Viewed by 5319
Abstract
Fracture healing is a long-term and complex process influenced by a huge variety of factors. Among these, there is a sex/gender disparity. Based on significant differences observed in the outcome of bone healing in males and females, in the present review, we report [...] Read more.
Fracture healing is a long-term and complex process influenced by a huge variety of factors. Among these, there is a sex/gender disparity. Based on significant differences observed in the outcome of bone healing in males and females, in the present review, we report the main findings, hypotheses and pitfalls that could lead to these differences. In particular, the role of sex hormones and inflammation has been reported to have a role in the observed less efficient bone healing in females in comparison with that observed in males. In addition, estrogen-induced cellular processes such as autophagic cell cycle impairment and molecular signals suppressing cell cycle progression seem also to play a role in female fracture healing delay. In conclusion, it seems conceivable that a complex framework of events could contribute to the female bias in bone healing, and we suggest that a reappraisal of the compelling factors could contribute to the mitigation of sex/gender disparity and improve bone healing outcomes. Full article
(This article belongs to the Special Issue Multidisciplinary Insights on Bone Healing (Volume II))
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