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Biomedicines
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Scientific Advances in Fracture Healing and Bone Regeneration: Current Strategies...
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Scientific Advances in Fracture Healing and Bone Regeneration: Current Strategies for Enhancing Bone Repair

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Cell Biology and Pathology".

Deadline for manuscript submissions: closed (31 March 2021) | Viewed by 20058

Special Issue Editor

Dr. Timo Gaber

E-Mail Website
Guest Editor
1. Charité–Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Rheumatology and Clinical Immunology, Berlin, Germany
2. German Rheumatism Research Centre (DRFZ) Berlin, a Leibniz Institute, Berlin, Germany
Interests: cellular energy metabolism of immune cells; cellular glucocorticoid mechanisms and the role of HIF’s in cellular immune response and regeneration processes such as wound and fracture healing
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Every year, millions of patients worldwide suffer bone fractures (one every two to three seconds). More than 10% of these fractures lead to bone healing disorders such as non-unions, cause substantial pain for the patients and enormous costs to the health care system, and frequently create social challenges for patients.

A deep understanding of the biology underlying bone regeneration, knowledge on current fixation methods and standardized pain management, feasibility and requirements for cell grafting approaches, and biologics and physical stimulation as well as strategies for enhancing repair ensure successful clinical management of fracture repair.

This Special Issue will focus on up-to-date experimental methods to measure, assess, and enhance bone repair using standardized state-of-the-art techniques and new biological, chemical, and tissue-engineered approaches; current and new types of fixation protocols; and appropriate experimental in vitro and in vivo models. In particular, for this Special Issue contributions dealing with strategies for enhancing fracture repair, including improvement of vascularization with a substantial enhancement of knowledge on bone biology and osteoimmunology as well as new experimental in vitro and in vivo approaches, are highly encouraged.

Dr. Timo Gaber
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. Biomedicines is an international peer-reviewed open access monthly 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

  • fracture healing
  • cell therapy
  • scaffolds
  • promotion of fracture healing
  • improvement of vascularization
  • in vitro and in vivo approaches
  • fixation methods
  • bone biology

Published Papers (4 papers)

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Research

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15 pages, 4858 KiB  
Article
Clumps of Mesenchymal Stem Cells/Extracellular Matrix Complexes Generated with Xeno-Free Chondro-Inductive Medium Induce Bone Regeneration via Endochondral Ossification
by Susumu Horikoshi, Mikihito Kajiya, Souta Motoike, Mai Yoshino, Shin Morimoto, Hiroki Yoshii, Tomoya Ogawa, Hisakatsu Sone, Tomoyuki Iwata, Kazuhisa Ouhara, Shinji Matsuda, Noriyoshi Mizuno and Hidemi Kurihara
Biomedicines 2021, 9(10), 1408; https://doi.org/10.3390/biomedicines9101408 - 07 Oct 2021
Cited by 5 | Viewed by 1827
Abstract
Three-dimensional clumps of mesenchymal stem cells (MSCs)/extracellular matrix (ECM) complexes (C-MSCs) can be transplanted into tissue defect site with no artificial scaffold. Importantly, most bone formation in the developing process or fracture healing proceeds via endochondral ossification. Accordingly, this present study investigated whether [...] Read more.
Three-dimensional clumps of mesenchymal stem cells (MSCs)/extracellular matrix (ECM) complexes (C-MSCs) can be transplanted into tissue defect site with no artificial scaffold. Importantly, most bone formation in the developing process or fracture healing proceeds via endochondral ossification. Accordingly, this present study investigated whether C-MSCs generated with chondro-inductive medium (CIM) can induce successful bone regeneration and assessed its healing process. Human bone marrow-derived MSCs were cultured with xeno-free/serum-free (XF) growth medium. To obtain C-MSCs, confluent cells that had formed on the cellular sheet were scratched using a micropipette tip and then torn off. The sheet was rolled to make a round clump of cells. The cell clumps, i.e., C-MSCs, were maintained in XF-CIM. C-MSCs generated with XF-CIM showed enlarged round cells, cartilage matrix, and hypertrophic chondrocytes genes elevation in vitro. Transplantation of C-MSCs generated with XF-CIM induced successful bone regeneration in the SCID mouse calvaria defect model. Immunofluorescence staining for human-specific vimentin demonstrated that donor human and host mouse cells cooperatively contributed the bone formation. Besides, the replacement of the cartilage matrix into bone was observed in the early period. These findings suggested that cartilaginous C-MSCs generated with XF-CIM can induce bone regeneration via endochondral ossification. Full article
(This article belongs to the Special Issue Scientific Advances in Fracture Healing and Bone Regeneration: Current Strategies for Enhancing Bone Repair)
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21 pages, 5256 KiB  
Article
Vancomycin-Loaded Collagen/Hydroxyapatite Layers Electrospun on 3D Printed Titanium Implants Prevent Bone Destruction Associated with S. epidermidis Infection and Enhance Osseointegration
by Tomáš Suchý, Lucie Vištejnová, Monika Šupová, Pavel Klein, Martin Bartoš, Yaroslav Kolinko, Tereza Blassová, Zbyněk Tonar, Marek Pokorný, Zbyněk Sucharda, Margit Žaloudková, František Denk, Rastislav Ballay, Štefan Juhás, Jana Juhásová, Eva Klapková, Lukáš Horný, Radek Sedláček, Tomáš Grus, Zdeněk Čejka, Jr., Zdeněk Čejka, Kateřina Chudějová and Jaroslav Hrabákadd Show full author list remove Hide full author list
Biomedicines 2021, 9(5), 531; https://doi.org/10.3390/biomedicines9050531 - 10 May 2021
Cited by 15 | Viewed by 3488
Abstract
The aim of the study was to develop an orthopedic implant coating in the form of vancomycin-loaded collagen/hydroxyapatite layers (COLHA+V) that combine the ability to prevent bone infection with the ability to promote enhanced osseointegration. The ability to prevent bone infection was investigated [...] Read more.
The aim of the study was to develop an orthopedic implant coating in the form of vancomycin-loaded collagen/hydroxyapatite layers (COLHA+V) that combine the ability to prevent bone infection with the ability to promote enhanced osseointegration. The ability to prevent bone infection was investigated employing a rat model that simulated the clinically relevant implant-related introduction of bacterial contamination to the bone during a surgical procedure using a clinical isolate of Staphylococcus epidermidis. The ability to enhance osseointegration was investigated employing a model of a minipig with terminated growth. Six weeks following implantation, the infected rat femurs treated with the implants without vancomycin (COLHA+S. epidermidis) exhibited the obvious destruction of cortical bone as evinced via a cortical bone porosity of up to 20% greater than that of the infected rat femurs treated with the implants containing vancomycin (COLHA+V+S. epidermidis) (3%) and the non-infected rat femurs (COLHA+V) (2%). The alteration of the bone structure of the infected COLHA+S. epidermidis group was further demonstrated by a 3% decrease in the average Ca/P molar ratio of the bone mineral. Finally, the determination of the concentration of vancomycin released into the blood stream indicated a negligible systemic load. Six months following implantation in the pigs, the quantified ratio of new bone indicated an improvement in osseointegration, with a two-fold bone ingrowth on the COLHA (47%) and COLHA+V (52%) compared to the control implants without a COLHA layer (27%). Therefore, it can be concluded that COLHA+V layers are able to significantly prevent the destruction of bone structure related to bacterial infection with a minimal systemic load and, simultaneously, enhance the rate of osseointegration. Full article
(This article belongs to the Special Issue Scientific Advances in Fracture Healing and Bone Regeneration: Current Strategies for Enhancing Bone Repair)
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Review

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20 pages, 1122 KiB  
Review
Fracture Healing Research—Shift towards In Vitro Modeling?
by Moritz Pfeiffenberger, Alexandra Damerau, Annemarie Lang, Frank Buttgereit, Paula Hoff and Timo Gaber
Biomedicines 2021, 9(7), 748; https://doi.org/10.3390/biomedicines9070748 - 28 Jun 2021
Cited by 17 | Viewed by 10131
Abstract
Fractures are one of the most frequently occurring traumatic events worldwide. Approximately 10% of fractures lead to bone healing disorders, resulting in strain for affected patients and enormous costs for society. In order to shed light into underlying mechanisms of bone regeneration (habitual [...] Read more.
Fractures are one of the most frequently occurring traumatic events worldwide. Approximately 10% of fractures lead to bone healing disorders, resulting in strain for affected patients and enormous costs for society. In order to shed light into underlying mechanisms of bone regeneration (habitual or disturbed), and to develop new therapeutic strategies, various in vivo, ex vivo and in vitro models can be applied. Undeniably, in vivo models include the systemic and biological situation. However, transferability towards the human patient along with ethical concerns regarding in vivo models have to be considered. Fostered by enormous technical improvements, such as bioreactors, on-a-chip-technologies and bone tissue engineering, sophisticated in vitro models are of rising interest. These models offer the possibility to use human cells from individual donors, complex cell systems and 3D models, therefore bridging the transferability gap, providing a platform for the introduction of personalized precision medicine and finally sparing animals. Facing diverse processes during fracture healing and thus various scientific opportunities, the reliability of results oftentimes depends on the choice of an appropriate model. Hence, we here focus on categorizing available models with respect to the requirements of the scientific approach. Full article
(This article belongs to the Special Issue Scientific Advances in Fracture Healing and Bone Regeneration: Current Strategies for Enhancing Bone Repair)
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20 pages, 10894 KiB  
Review
Strategies to Improve Bone Healing: Innovative Surgical Implants Meet Nano-/Micro-Topography of Bone Scaffolds
by Dirk Wähnert, Johannes Greiner, Stefano Brianza, Christian Kaltschmidt, Thomas Vordemvenne and Barbara Kaltschmidt
Biomedicines 2021, 9(7), 746; https://doi.org/10.3390/biomedicines9070746 - 28 Jun 2021
Cited by 10 | Viewed by 3741
Abstract
Successful fracture healing is dependent on an optimal mechanical and biological environment at the fracture site. Disturbances in fracture healing (non-union) or even critical size bone defects, where void volume is larger than the self-healing capacity of bone tissue, are great challenges for [...] Read more.
Successful fracture healing is dependent on an optimal mechanical and biological environment at the fracture site. Disturbances in fracture healing (non-union) or even critical size bone defects, where void volume is larger than the self-healing capacity of bone tissue, are great challenges for orthopedic surgeons. To address these challenges, new surgical implant concepts have been recently developed to optimize mechanical conditions. First, this review article discusses the mechanical environment on bone and fracture healing. In this context, a new implant concept, variable fixation technology, is introduced. This implant has the unique ability to change its mechanical properties from “rigid” to “dynamic” over the time of fracture healing. This leads to increased callus formation, a more homogeneous callus distribution and thus improved fracture healing. Second, recent advances in the nano- and micro-topography of bone scaffolds for guiding osteoinduction will be reviewed, particularly emphasizing the mimicry of natural bone. We summarize that an optimal scaffold should comprise micropores of 50–150 µm diameter allowing vascularization and migration of stem cells as well as nanotopographical osteoinductive cues, preferably pores of 30 nm diameter. Next to osteoinduction, such nano- and micro-topographical cues may also reduce inflammation and possess an antibacterial activity to further promote bone regeneration. Full article
(This article belongs to the Special Issue Scientific Advances in Fracture Healing and Bone Regeneration: Current Strategies for Enhancing Bone Repair)
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