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Special Issue "Head Tissues Regeneration"

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (31 December 2018).

Special Issue Editor

Prof. Dr. Rodella Luigi
Website
Guest Editor
Division of Anatomy and Physiopathology, Department of Clinical and Experimental Sciences, University of Brescia, Viale Europa 11 , 25123 Brescia, Italy.
Interests: Head and neck anatomy, platelets preparations, bone regeneration

Special Issue Information

Dear Colleagues,

Regeneration of head tissues represents one of the main goal of regenerative medicine.

The Special Issue on “Head tissues regeneration” will cover recent advances in the application of regenerative medicine in head and neck tissues regeneration in different medical areas including dermatology, dentistry, aesthetic medicine, otolaryngology, neurosurgery.

All regenerative approaches that help soft tissues and bone regeneration after trauma or degenerative pathologies, are welcome.

Ranging from molecular and cellular studies to in vivo approaches, the aim of this Special Issue is to focus the role alone or combined with bioactive molecules, biomaterials, stem cells, bone and soft tissue transplantation, platelet preparations, in regenerative medicine. Up-to-date reviews and research articles will all be considered.

Prof. Dr. Luigi F. Rodella
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 papers will be 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

  • tissue regeneration
  • head and neck
  • bone
  • soft tissues
  • bioactive molecules
  • biomaterials
  • stem cells
  • platelet preparations
  • dermatology, dentistry
  • aesthetic medicine
  • otolaryngology
  • neurosurgery

Published Papers (11 papers)

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Research

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Open AccessArticle
Influence of Cigarette Smoke Inhalation on an Autogenous Onlay Bone Graft Area in Rats with Estrogen Deficiency: A Histomorphometric and Immunohistochemistry Study
Int. J. Mol. Sci. 2019, 20(8), 1854; https://doi.org/10.3390/ijms20081854 - 15 Apr 2019
Abstract
Purpose: The present study aimed to evaluate the influence of cigarette smoke inhalation on an autogenous onlay bone graft area, either covered with a collagen membrane or not, in healthy and estrogen-deficient rats through histomorphometry and immunohistochemistry. Materials and Methods: Sixty female rats [...] Read more.
Purpose: The present study aimed to evaluate the influence of cigarette smoke inhalation on an autogenous onlay bone graft area, either covered with a collagen membrane or not, in healthy and estrogen-deficient rats through histomorphometry and immunohistochemistry. Materials and Methods: Sixty female rats (Wistar), weighing 250–300 g, were randomly divided and allocated into groups (either exposed to cigarette smoke inhalation or not, ovariectomized and SHAM). After 15 days, the test group underwent cigarette smoke inhalation. Sixty days after exposition, autogenous bone grafting was only performed on all right hemimandibles, and the left ones underwent autogenous onlay bone grafting with the collagen membrane (BioGide®). The graft was harvested from the parietal bone and attached to the animals’ jaws (right and left). They were euthanized at 21, 45, and 60 days after grafting. Histological measurements and immunohistochemical analyses were performed, and results were submitted to a statistical analysis. Results: The addition of a collagen membrane to the bone graft proved more efficient in preserving graft area if compared to the graft area without a collagen membrane and the one associated with cigarette smoke inhalation at 21 (p = 0.0381) and 60 days (p = 0.0192), respectively. Cigarette smoke inhalation combined with ovariectomy promoted a significant reduction of the autogenous graft area at 21 and 60 days. At 45 days, no statistically significant results were observed. In the immunohistochemical analysis, the ovariectomized and smoking subgroups, combined or not with collagen membrane, received moderate and intense immunolabeling at 21 days for Receptor Activator of Nuclear Factor Kappa-B Ligand (RANKL) (p = 0.0017 and p = 0.0381, respectively). For Osteoprotegerin (OPG), intense immunolabeling was observed in most subgroups under analysis at 60 days. Conclusion: Smoking inhalation promoted resorption on the autogenous onlay bone graft, mainly when associated with ovariectomy. Furthermore, when associated with the collagen membrane, a lower resorption rate was observed if compared to the absence of the membrane. Full article
(This article belongs to the Special Issue Head Tissues Regeneration)
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Open AccessArticle
Minimally Manipulative Method for the Expansion of Human Bone Marrow Mesenchymal Stem Cells to Treat Osseous Defects
Int. J. Mol. Sci. 2019, 20(3), 612; https://doi.org/10.3390/ijms20030612 - 31 Jan 2019
Cited by 3
Abstract
Lack of standardization of clinically compliant culture protocols of mesenchymal stem cells for re-implantation in humans have hindered clinical progress in the field of tissue regeneration to repair maxillofacial and orthopedic defects. The goal of this study was to establish a clinically relevant [...] Read more.
Lack of standardization of clinically compliant culture protocols of mesenchymal stem cells for re-implantation in humans have hindered clinical progress in the field of tissue regeneration to repair maxillofacial and orthopedic defects. The goal of this study was to establish a clinically relevant osteogenic protocol for collection and expansion of autologous stem cells to be used at Marshall University for re-implantation and repair of maxillofacial and orthopedic conditions. Human bone marrow (hBM) samples were collected from patients undergoing intramedullary nail fixation for closed femoral fractures. hBM mesenchymal cells were expanded by growing them first in Petri dishes for two weeks, followed by a week of culture using Perfecta 3D Hanging Drop Plates®. Various scaffold materials were tested and analyzed for cellular integration, vitality, and differentiation capacity of harvested hBM-MSCs including: 60/40 blend of hydroxyapatite biomatrix; Acellular bone composite discs; Allowash®, cancellous bone cubes; PLGA (poly lactic-co-glycolic acid); and Woven chitin derived fiber. We found that the 3D spheroid culture allowed production of hBM mesenchymal cells that retained osteoblast differentiation capacity over a monolayer culture of hBM-MSCs without the need to use chemical or hormonal modulation. We also observed that hydroxyapatite and Allowash cancellous bone scaffolds allowed better cell integration and viability properties as compared to other materials tested in this study. In conclusion, the multimodal culture methodology we developed creates actively differentiating stem-cell spheroids that can then be readily utilized in clinical practices to improve the regeneration of tissues of the head and the body. Full article
(This article belongs to the Special Issue Head Tissues Regeneration)
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Open AccessArticle
Dose-Dependent Effect of Mesenchymal Stromal Cell Recruiting Chemokine CCL25 on Porcine Tissue-Engineered Healthy and Osteoarthritic Cartilage
Int. J. Mol. Sci. 2019, 20(1), 52; https://doi.org/10.3390/ijms20010052 - 23 Dec 2018
Cited by 1
Abstract
Thymus-expressed chemokine (CCL25) is a potent cell attractant for mesenchymal stromal cells, and therefore it is a candidate for in situ cartilage repair approaches focusing on the recruitment of endogenous repair cells. However, the influence of CCL25 on cartilage is unknown. Accordingly, in [...] Read more.
Thymus-expressed chemokine (CCL25) is a potent cell attractant for mesenchymal stromal cells, and therefore it is a candidate for in situ cartilage repair approaches focusing on the recruitment of endogenous repair cells. However, the influence of CCL25 on cartilage is unknown. Accordingly, in this study, we investigated the effect of CCL25 on tissue-engineered healthy and osteoarthritic cartilage. Porcine chondrocytes were cultured in a three-dimensional (3D) micromass model that has been proven to mimic key-aspects of human cartilage and osteoarthritic alterations upon stimulation with tumor necrosis factor-α (TNF-α). Micromass cultures were stimulated with CCL25 (0, 0.05, 0.5, 5, 50, 500 nmol/L) alone or in combination with 0.6 nmol/L TNF-α for seven days. Effects were evaluated by life/dead staining, safranin O staining, histomorphometrical analysis of glycosaminoglycans (GAGs), collagen type II (COL2A1) real-time RT-PCR and Porcine Genome Array analysis. 500 nmol/L CCL25 led to a significant reduction of GAGs and COL2A1 expression and induced the expression of matrix metallopeptidases (MMP) 1, MMP3, early growth response protein 1 (EGR1), and superoxide dismutase 2 (SOD2). In concentrations lower than 500 nmol/L, CCL25 seems to be a candidate for in situ cartilage repair therapy approaches. Full article
(This article belongs to the Special Issue Head Tissues Regeneration)
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Open AccessArticle
Effects of Enhanced Hydrophilic Titanium Dioxide-Coated Hydroxyapatite on Bone Regeneration in Rabbit Calvarial Defects
Int. J. Mol. Sci. 2018, 19(11), 3640; https://doi.org/10.3390/ijms19113640 - 19 Nov 2018
Cited by 3
Abstract
The regeneration of bone defects caused by periodontal disease or trauma is an important goal. Porous hydroxyapatite (HA) is an osteoconductive graft material. However, the hydrophobic properties of HA can be a disadvantage in the initial healing process. HA can be coated with [...] Read more.
The regeneration of bone defects caused by periodontal disease or trauma is an important goal. Porous hydroxyapatite (HA) is an osteoconductive graft material. However, the hydrophobic properties of HA can be a disadvantage in the initial healing process. HA can be coated with TiO2 to improve its hydrophilicity, and ultraviolet irradiation (UV) can further increase the hydrophilicity by photofunctionalization. This study was designed to evaluate the effect of 5% TiO2-coated HA on rabbit calvarial defects and compare it with that of photofunctionalization on new bone in the early stage. The following four study groups were established, negative control, HA, TiO2-coated HA, and TiO2-coated HA with UV. The animals were sacrificed and the defects were assessed by radiography as well as histologic and histomorphometric analyses. At 2 and 8 weeks postoperatively, the TiO2-coated HA with UV group and TiO2-coated HA group showed significantly higher percentages of new bone than the control group (p < 0.05). UV irradiation increased the extent of new bone formation, and there was a significant difference between the TiO2-coated HA group and TiO2-coated HA with UV group. The combination of TiO2/HA and UV irradiation in bone regeneration appears to induce a favorable response. Full article
(This article belongs to the Special Issue Head Tissues Regeneration)
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Open AccessCommunication
An In Vitro Model of Angiogenesis during Wound Healing Provides Insights into the Complex Role of Cells and Factors in the Inflammatory and Proliferation Phase
Int. J. Mol. Sci. 2018, 19(10), 2913; https://doi.org/10.3390/ijms19102913 - 25 Sep 2018
Cited by 7
Abstract
Successful vascularization is essential in wound healing, the histo-integration of biomaterials, and other aspects of regenerative medicine. We developed a functional in vitro assay to dissect the complex processes directing angiogenesis during wound healing, whereby vascular cell spheroids were induced to sprout in [...] Read more.
Successful vascularization is essential in wound healing, the histo-integration of biomaterials, and other aspects of regenerative medicine. We developed a functional in vitro assay to dissect the complex processes directing angiogenesis during wound healing, whereby vascular cell spheroids were induced to sprout in the presence of classically (M1) or alternatively (M2) activated macrophages. This simulated a microenvironment, in which sprouting cells were exposed to the inflammatory or proliferation phases of wound healing, respectively. We showed that M1 macrophages induced single-cell migration of endothelial cells and pericytes. In contrast, M2 macrophages augmented endothelial sprouting, suggesting that vascular cells infiltrate the wound bed during the inflammatory phase and extensive angiogenesis is initiated upon a switch to a predominance of M2. Interestingly, M1 and M2 shared a pro-angiogenic secretome, whereas pro-inflammatory cytokines were solely secreted by M1. These results suggested that acute inflammatory factors act as key inducers of vascular cell infiltration and as key negative regulators of angiogenesis, whereas pro-angiogenic factors are present throughout early wound healing. This points to inflammatory factors as key targets to modulate angiogenesis. The here-established wound healing assay represents a useful tool to investigate the effect of biomaterials and factors on angiogenesis during wound healing. Full article
(This article belongs to the Special Issue Head Tissues Regeneration)
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Open AccessArticle
Can Plasma Rich in Growth Factors Be Safe for Parental Use? A Safety Study in the Canine Model
Int. J. Mol. Sci. 2018, 19(9), 2701; https://doi.org/10.3390/ijms19092701 - 11 Sep 2018
Cited by 1
Abstract
Low invasiveness is the main goal of modern surgery. The use of platelet-rich plasma (PRP) is known to be effective in a variety of applications, such as oral, maxillofacial, orthopedic, dermatologic and cosmetic surgeries. However, a potential ergogenic and carcinogenic effect of PRP [...] Read more.
Low invasiveness is the main goal of modern surgery. The use of platelet-rich plasma (PRP) is known to be effective in a variety of applications, such as oral, maxillofacial, orthopedic, dermatologic and cosmetic surgeries. However, a potential ergogenic and carcinogenic effect of PRP derivatives by means of the insulin-like growth factor-1 (IGF-1) pathway has been suggested. Because of this notion, the purpose of this study is to assess the effect of a commercially available PRP-derivative intramuscular injection in the lumbar muscular tissue (local effect) and to determine the IGF-1 blood concentration (systemic effect) on healthy beagle dogs. Local effect was evaluated by computed tomography (CT) scan and echography, and systemic effect was calculated by blood testing on days 0, 14, 28, 42 and 56. No statistically significant changes were observed; thus, PRGF could be considered safe when using therapeutic doses. Full article
(This article belongs to the Special Issue Head Tissues Regeneration)
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Open AccessArticle
Dental Pulp Stem Cell-Derived, Scaffold-Free Constructs for Bone Regeneration
Int. J. Mol. Sci. 2018, 19(7), 1846; https://doi.org/10.3390/ijms19071846 - 22 Jun 2018
Cited by 8
Abstract
In the present study, a scaffold-free tissue construct was developed as an approach for the regeneration of tissue defects, which produced good outcomes. We fabricated a scaffold-free tissue construct from human dental pulp stem cells (hDPSCs construct), and examined the characteristics of the [...] Read more.
In the present study, a scaffold-free tissue construct was developed as an approach for the regeneration of tissue defects, which produced good outcomes. We fabricated a scaffold-free tissue construct from human dental pulp stem cells (hDPSCs construct), and examined the characteristics of the construct. For its fabrication, basal sheets prepared by 4-week hDPSCs culturing were subjected to 1-week three-dimensional culture, with or without osteogenic induction, whereas hDPSC sheets (control) were fabricated by 1-week culturing of basal sheets on monolayer culture. The hDPSC constructs formed a spherical structure and calcified matrix that are absent in the control. The expression levels for bone-related genes in the hDPSC constructs were significantly upregulated compared with those in the control. Moreover, the hDPSC constructs with osteogenic induction had a higher degree of calcified matrix formation, and higher expression levels for bone-related genes, than those for the hDPSC constructs without osteogenic induction. These results suggest that the hDPSC constructs with osteogenic induction are composed of cells and extracellular and calcified matrices, and that they can be a possible scaffold-free material for bone regeneration. Full article
(This article belongs to the Special Issue Head Tissues Regeneration)
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Open AccessArticle
Three-Dimensional Architecture and Mechanical Properties of Bovine Bone Mixed with Autologous Platelet Liquid, Blood, or Physiological Water: An In Vitro Study
Int. J. Mol. Sci. 2018, 19(4), 1230; https://doi.org/10.3390/ijms19041230 - 18 Apr 2018
Cited by 5
Abstract
In recent years, several techniques and material options have been investigated and developed for bone defect repair and regeneration. The progress in studies of composite graft materials and autologous platelet-derived growth factors for bone regeneration in dentistry and their biological and biomechanical properties [...] Read more.
In recent years, several techniques and material options have been investigated and developed for bone defect repair and regeneration. The progress in studies of composite graft materials and autologous platelet-derived growth factors for bone regeneration in dentistry and their biological and biomechanical properties has improved clinical strategies and results. The aim of this study was to evaluate the three-dimensional architecture and mechanical properties of three different combinations of composite bovine graft, adding autologous platelet liquid (APL), blood, or physiological water. One experimental group for each combination of biomaterials was created. In particular, in Group I, the bovine graft was mixed with APL; in Group II, it was mixed with blood, and in Group III, the biomaterial graft was combined with physiological water. Then, the composite biomaterials were evaluated by scanning electron microscopy (SEM), and a compression-loading test was conducted. The evaluation showed a statistical significance (p < 0.01) of the elastic regime of deformation resistance, in which the combination of APL with bone graft resulted in an 875% increase in the mechanical resistance. The protocol of APL mixed with bovine bone graft produced a composite sticky graft block that was capable of increasing the mechanical properties in order to improve its clinical use in the treatment of the maxillary bone defects. Full article
(This article belongs to the Special Issue Head Tissues Regeneration)
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Review

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Open AccessReview
Modern Concepts in Regenerative Therapy for Ischemic Stroke: From Stem Cells for Promoting Angiogenesis to 3D-Bioprinted Scaffolds Customized via Carotid Shear Stress Analysis
Int. J. Mol. Sci. 2019, 20(10), 2574; https://doi.org/10.3390/ijms20102574 - 25 May 2019
Cited by 1
Abstract
Ischemic stroke is associated with a tremendous economic and societal burden, and only a few therapies are currently available for the treatment of this devastating disease. The main therapeutic approaches used nowadays for the treatment of ischemic brain injury aim to achieve reperfusion, [...] Read more.
Ischemic stroke is associated with a tremendous economic and societal burden, and only a few therapies are currently available for the treatment of this devastating disease. The main therapeutic approaches used nowadays for the treatment of ischemic brain injury aim to achieve reperfusion, neuroprotection and neurorecovery. Therapeutic angiogenesis also seems to represent a promising tool to improve the prognosis of cerebral ischemia. This review aims to present the modern concepts and the current status of regenerative therapy for ischemic stroke and discuss the main results of major clinical trials addressing the effectiveness of stem cell therapy for achieving neuroregeneration in ischemic stroke. At the same time, as a glimpse into the future, this article describes modern concepts for stroke prevention, such as the implantation of bioprinted scaffolds seeded with stem cells, whose 3D geometry is customized according to carotid shear stress. Full article
(This article belongs to the Special Issue Head Tissues Regeneration)
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Open AccessReview
Platelet-Rich Plasma in Treatment of Temporomandibular Joint Dysfunctions: Narrative Review
Int. J. Mol. Sci. 2019, 20(2), 277; https://doi.org/10.3390/ijms20020277 - 11 Jan 2019
Cited by 8
Abstract
Background: The aims of this narrative review were to examine up-to-date literature in order to evaluate the effectiveness of arthrocentesis or injections with platelet-rich plasma in temporomandibular affections and to compare them to arthrocentesis alone or with hyaluronic acid (HA) or to hyaluronic [...] Read more.
Background: The aims of this narrative review were to examine up-to-date literature in order to evaluate the effectiveness of arthrocentesis or injections with platelet-rich plasma in temporomandibular affections and to compare them to arthrocentesis alone or with hyaluronic acid (HA) or to hyaluronic acid injections. Methods: The search of international literature was made on the PMC, PubMed and Cochrane databases, including all full-length text of studies on humans focused on osteoarthritis and disc displacements and their treatment with platelet-rich plasma arthrocentesis or injections. All design studies were included in the review and they were examined for three different outcomes: pain, joint sound and mandibular motion. English papers were only selected. Results: Even though the low number of studies in this field, arthrocentesis with platelet-rich plasma and platelet-rich plasma injections in temporomandibular disorders’ management were found to be effective in reducing pain and joint sound as well as in improving mandibular motion in a maximum follow-up of 24 months. Conclusion: Comparison to arthrocentesis alone or to HA use in arthrocentesis or by injections provided encouraging results in terms of the effectiveness of platelet-rich plasma use. Full article
(This article belongs to the Special Issue Head Tissues Regeneration)
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Open AccessReview
Regenerative Models for the Integration and Regeneration of Head Skeletal Tissues
Int. J. Mol. Sci. 2018, 19(12), 3752; https://doi.org/10.3390/ijms19123752 - 26 Nov 2018
Cited by 1
Abstract
Disease of, or trauma to, the human jaw account for thousands of reconstructive surgeries performed every year. One of the most popular and successful treatment options in this context involves the transplantation of bone tissue from a different anatomical region into the affected [...] Read more.
Disease of, or trauma to, the human jaw account for thousands of reconstructive surgeries performed every year. One of the most popular and successful treatment options in this context involves the transplantation of bone tissue from a different anatomical region into the affected jaw. Although, this method has been largely successful, the integration of the new bone into the existing bone is often imperfect, and the integration of the host soft tissues with the transplanted bone can be inconsistent, resulting in impaired function. Unlike humans, several vertebrate species, including fish and amphibians, demonstrate remarkable regenerative capabilities in response to jaw injury. Therefore, with the objective of identifying biological targets to promote and engineer improved outcomes in the context of jaw reconstructive surgery, we explore, compare and contrast the natural mechanisms of endogenous jaw and limb repair and regeneration in regenerative model organisms. We focus on the role of different cell types as they contribute to the regenerating structure; how mature cells acquire plasticity in vivo; the role of positional information in pattern formation and tissue integration, and limitations to endogenous regenerative and repair mechanisms. Full article
(This article belongs to the Special Issue Head Tissues Regeneration)
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