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Research on Bone Healing Materials
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Research on Bone Healing Materials

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Materials Science".

Deadline for manuscript submissions: closed (31 March 2023) | Viewed by 13946

Special Issue Editor

Prof. Dr. Emerito Carlos Rodriguez-Merchan

E-Mail Website
Guest Editor
1. Department of Orthopedic Surgery, La Paz University Hospital, 28046 Madrid, Spain
2. Osteoarticular Surgery Research, Institute for Health Research, La Paz University Hospital, Autonomous University of Madrid, 28046 Madrid, Spain
Interests: bone; tendon; ligament; muscle; hemophilia
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues, 

Bone fractures are the most common traumatic injuries in humans. The repair of bone fractures is a regenerative process that usually leads to successful healing and the recovery of the damaged bone. However, around 5–10% of fractures will lead to delayed union or nonunion. In this Special Issue, we will review the different strategies to heal bone defects using synthetic bone graft substitutes (BGS), as well as biologically active substances and stem cells. BGS can be either derived from biological products (such as demineralized bone matrix, platelet-rich plasma, hydroxyapatite, adjunction of growth factors (such as bone morphogenetic protein)) or synthetic products (such as calcium sulfate, tri-calcium phosphate ceramics, bioactive glasses, or polymer-based substitutes). Current treatment approaches can be classified in three main categories: 1) synthetic BGS whose architecture and surface can be optimized; 2) BGS combined with bioactive molecules such as growth factors, peptides, or small molecules targeting bone precursor cells, bone formation, and metabolism; and 3) cell-based strategies with progenitor cells combined or not with active molecules that can be injected or seeded on BGS for improved delivery. The aim of this Special Issue is to bring together the latest research on bone healing materials. It is essential to be able to resolve from a clinical point of view the 5–10% of cases of delayed union and nonunion, especially some of them that sometimes become recalcitrant.

Prof. Dr. Emerito Carlos Rodriguez-Merchan
Guest Editor

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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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

  • bone healing materials
  • bone fracture
  • bone graft substitutes
  • biologically active substance
  • hydroxyapatite

Published Papers (5 papers)

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Research

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13 pages, 3928 KiB  
Article
Antiosteoporotic Nanohydroxyapatite Zoledronate Scaffold Seeded with Bone Marrow Mesenchymal Stromal Cells for Bone Regeneration: A 3D In Vitro Model
by Matilde Tschon, Elisa Boanini, Maria Sartori, Francesca Salamanna, Silvia Panzavolta, Adriana Bigi and Milena Fini
Int. J. Mol. Sci. 2022, 23(11), 5988; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23115988 - 26 May 2022
Cited by 1 | Viewed by 1607
Abstract
Background: Bisphosphonates are widely employed drugs for the treatment of pathologies with high bone resorption, such as osteoporosis, and display a great affinity for calcium ions and apatitic substrates. Here, we aimed to investigate the potentiality of zoledronate functionalized hydroxyapatite nanocrystals (HAZOL) to [...] Read more.
Background: Bisphosphonates are widely employed drugs for the treatment of pathologies with high bone resorption, such as osteoporosis, and display a great affinity for calcium ions and apatitic substrates. Here, we aimed to investigate the potentiality of zoledronate functionalized hydroxyapatite nanocrystals (HAZOL) to promote bone regeneration by stimulating adhesion, viability, metabolic activity and osteogenic commitment of human bone marrow derived mesenchymal stromal cells (hMSCs). Methods: we adopted an advanced three-dimensional (3D) in vitro fracture healing model to study porous scaffolds: hMSCs were seeded onto the scaffolds that, after three days, were cut in halves and unseeded scaffolds were placed between the two halves. Scaffold characterization by X-ray diffraction, transmission and scanning electron microscopy analyses and cell morphology, viability, osteogenic differentiation and extracellular matrix deposition were evaluated after 3, 7 and 10 days of culture. Results: Electron microscopy showed a porous and interconnected structure and a uniform cell layer spread onto scaffolds. Scaffolds were able to support cell growth and cells progressively colonized the whole inserts in absence of cytotoxic effects. Osteogenic commitment and gene expression of hMSCs were enhanced with higher expressions of ALPL, COL1A1, BGLAP, RUNX2 and Osterix genes. Conclusion: Although some limitations affect the present study (e.g., the lack of longer experimental times, of mechanical stimulus or pathological microenvironment), the obtained results with the adopted experimental setup suggested that zoledronate functionalized scaffolds (GHAZOL) might sustain not only cell proliferation, but positively influence osteogenic differentiation and activity if employed in bone fracture healing. Full article
(This article belongs to the Special Issue Research on Bone Healing Materials)
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Review

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15 pages, 1319 KiB  
Review
Treatment Effect of Platelet Gel on Reconstructing Bone Defects and Nonunions: A Review of In Vivo Human Studies
by Che-Yu Lin
Int. J. Mol. Sci. 2022, 23(19), 11377; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms231911377 - 27 Sep 2022
Cited by 1 | Viewed by 1977
Abstract
In ideal circumstances, a fractured bone can heal properly by itself or with the aid of clinical interventions. However, around 5% to 10% of bone fractures fail to heal properly within the expected time even with the aid of clinical interventions, resulting in [...] Read more.
In ideal circumstances, a fractured bone can heal properly by itself or with the aid of clinical interventions. However, around 5% to 10% of bone fractures fail to heal properly within the expected time even with the aid of clinical interventions, resulting in nonunions. Platelet gel is a blood-derived biomaterial used in regenerative medicine aiming to promote wound healing and regeneration of damaged tissues. The purpose of this paper is to review relevant articles in an attempt to explore the current consensus on the treatment effect of platelet gel on reconstructing bone defects and nonunions, hoping to provide a valuable reference for clinicians to make treatment decisions in clinical practice. Based on the present review, most of the studies applied the combination of platelet gel and bone graft to reconstruct bone defects and nonunions, and most of the results were positive, suggesting that this treatment strategy could promote successful reconstruction of bone defects and nonunions. Only two studies tried to apply platelet gel alone to reconstruct bone defects and nonunions, therefore a convincing conclusion could not be made yet regarding the treatment effect of platelet gel alone on reconstructing bone defects and nonunions. Only one study applied platelet gel combined with extracorporeal shock wave therapy to reconstruct nonunions, and the results were positive; the hypothetical mechanism of this treatment strategy is reasonable and sound, and more future clinical studies are encouraged to further justify the effectiveness of this promising treatment strategy. In conclusion, the application of platelet gel could be a promising and useful treatment method for reconstructing bone defects and nonunions, and more future clinical studies are encouraged to further investigate the effectiveness of this promising treatment method. Full article
(This article belongs to the Special Issue Research on Bone Healing Materials)
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11 pages, 900 KiB  
Review
Bone Healing Materials in the Treatment of Recalcitrant Nonunions and Bone Defects
by Emérito Carlos Rodríguez-Merchán
Int. J. Mol. Sci. 2022, 23(6), 3352; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23063352 - 20 Mar 2022
Cited by 28 | Viewed by 3779
Abstract
The usual treatment for bone defects and recalcitrant nonunions is an autogenous bone graft. However, due to the limitations in obtaining autogenous bone grafts and the morbidity associated with their procurement, various bone healing materials have been developed in recent years. The three [...] Read more.
The usual treatment for bone defects and recalcitrant nonunions is an autogenous bone graft. However, due to the limitations in obtaining autogenous bone grafts and the morbidity associated with their procurement, various bone healing materials have been developed in recent years. The three main treatment strategies for bone defects and recalcitrant nonunions are synthetic bone graft substitutes (BGS), BGS combined with bioactive molecules, and BGS and stem cells (cell-based constructs). Regarding BGS, numerous biomaterials have been developed to prepare bone tissue engineering scaffolds, including biometals (titanium, iron, magnesium, zinc), bioceramics (hydroxyapatite (HA)), tricalcium phosphate (TCP), biopolymers (collagen, polylactic acid (PLA), polycaprolactone (PCL)), and biocomposites (HA/MONs@miR-34a composite coating, Bioglass (BG)-based ABVF-BG (antibiotic-releasing bone void filling) putty). Bone tissue engineering scaffolds are temporary implants that promote tissue ingrowth and new bone regeneration. They have been developed to improve bone healing through appropriate designs in terms of geometric, mechanical, and biological performance. Concerning BGS combined with bioactive molecules, one of the most potent osteoinductive growth factors is bone morphogenetic proteins (BMPs). In recent years, several natural (collagen, fibrin, chitosan, hyaluronic acid, gelatin, and alginate) and synthetic polymers (polylactic acid, polyglycolic acid, polylactic-coglycolide, poly(e-caprolactone) (PCL), poly-p-dioxanone, and copolymers consisting of glycolide/trimethylene carbonate) have been investigated as potential support materials for bone tissue engineering. Regarding BGS and stem cells (cell-based constructs), the main strategies are bone marrow stromal cells, adipose-derived mesenchymal cells, periosteum-derived stem cells, and 3D bioprinting of hydrogels and cells or bioactive molecules. Currently, significant research is being performed on the biological treatment of recalcitrant nonunions and bone defects, although its use is still far from being generalized. Further research is needed to investigate the efficacy of biological treatments to solve recalcitrant nonunions and bone defects. Full article
(This article belongs to the Special Issue Research on Bone Healing Materials)
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32 pages, 22110 KiB  
Review
Addressing the Needs of the Rapidly Aging Society through the Development of Multifunctional Bioactive Coatings for Orthopedic Applications
by Tinkara Mastnak, Uroš Maver and Matjaž Finšgar
Int. J. Mol. Sci. 2022, 23(5), 2786; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23052786 - 03 Mar 2022
Cited by 13 | Viewed by 4093
Abstract
The unprecedented aging of the world’s population will boost the need for orthopedic implants and expose their current limitations to a greater extent due to the medical complexity of elderly patients and longer indwelling times of the implanted materials. Biocompatible metals with multifunctional [...] Read more.
The unprecedented aging of the world’s population will boost the need for orthopedic implants and expose their current limitations to a greater extent due to the medical complexity of elderly patients and longer indwelling times of the implanted materials. Biocompatible metals with multifunctional bioactive coatings promise to provide the means for the controlled and tailorable release of different medications for patient-specific treatment while prolonging the material’s lifespan and thus improving the surgical outcome. The objective of this work is to provide a review of several groups of biocompatible materials that might be utilized as constituents for the development of multifunctional bioactive coatings on metal materials with a focus on antimicrobial, pain-relieving, and anticoagulant properties. Moreover, the review presents a summary of medications used in clinical settings, the disadvantages of the commercially available products, and insight into the latest development strategies. For a more successful translation of such research into clinical practice, extensive knowledge of the chemical interactions between the components and a detailed understanding of the properties and mechanisms of biological matter are required. Moreover, the cost-efficiency of the surface treatment should be considered in the development process. Full article
(This article belongs to the Special Issue Research on Bone Healing Materials)
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11 pages, 9479 KiB  
Case Report
Analysis of the Chemical Composition and Morphological Characterization of Tissue Osseointegrated to a Dental Implant after 5 Years of Function
by Josefa Alarcón Apablaza, Fernando José Días, Karina Godoy Sánchez, Pablo Navarro, Camila Venegas and Ramón Fuentes
Int. J. Mol. Sci. 2022, 23(16), 8882; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23168882 - 10 Aug 2022
Cited by 3 | Viewed by 1508
Abstract
Osseointegration implies the coexistence of a biocompatible implant subjected to masticatory loads and living bone tissue adhered to its surface; this interaction is a critical process for the success of implants. The objective of this work is to analyze the osseoformation and osseointegration [...] Read more.
Osseointegration implies the coexistence of a biocompatible implant subjected to masticatory loads and living bone tissue adhered to its surface; this interaction is a critical process for the success of implants. The objective of this work is to analyze the osseoformation and osseointegration of a dental implant in operation for 5 years microscopically through morphological analysis of the surface and chemical composition through a variable pressure scanning electron microscope (VP-SEM) and energy dispersive X-ray spectrometry (EDX). The chemical composition and general characteristics of the structural morphology of random areas of the surfaces of an osseointegrated dental implant from an ex vivo sample were analyzed. On the surface of the implant free of bone tissue, titanium (TI) was mainly identified in the area of the implant threads and carbon (C) in the depth of the implant threads. Phosphorus (P), calcium (Ca), oxygen (O), carbon (C), with dense and homogeneous distribution, and, to a lesser extent, sodium (Na) were detected on the bone surface around the contour of the implant. Regarding the morphological characteristics of the implant surface, a rough structure with some irregularities and detachments of the implant lodged in the bone tissue was observed. Microscopic analysis showed calcified bone tissue distributed in an orderly manner on the coronal and medial surface and sinuous and irregular in the apical area, with the presence of red blood cells. The composition of the implant allows a dynamic process of bone remodeling and regeneration subject to the biological and mechanical needs of the operation. Dental implants are shown to have exceptional and long-lasting biocompatibility that enables the formation of mature peri-implant bone tissue. Full article
(This article belongs to the Special Issue Research on Bone Healing Materials)
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