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The Molecules and Stem Cells in Bone Regeneration

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

Deadline for manuscript submissions: closed (25 September 2022) | Viewed by 12349

Special Issue Editors

School of Dentistry, Saint Camillus International University of Health and Medical Sciences, Via di Sant’Alessandro 8, 00131 Rome, Italy
Interests: bone regeneration; osseointegration; fracture implant; biomaterials; biocompatibility; bone resorption; bone biology
Special Issues, Collections and Topics in MDPI journals
Department of Medical, Oral and Biotechnological Sciences, University of Chieti-Pescara, Chieti, Italy
Interests: biomaterials; bone regeneration; bioengineering; biomedical engineering
Special Issues, Collections and Topics in MDPI journals
Department of Medical, Oral and Biotechnological Sciences, University G. d'Annunzio of Chieti-Pescara, Chieti, Italy
Interests: oral implantology; bone substitutes; biomechanical simulation; tissue engineering; bone substitute

Special Issue Information

Dear Colleagues,

The field of restoring hard and soft tissue lost by different damages includes several aspects of basic sciences such as physiology, stem cell biology, chemistry, molecules, and physical sciences.

There has been increased interest in surgical protocols, nanobiotechnologies, and tissue-engineering-proposed three-dimensional scaffolds and cell therapies as promising approaches in oral surgery.

The stem cells and new different molecules aim to improve the healthy regeneration of damaged orofacial tissue and reduce pathological wound healing responses, prevent resorption of bone, preserve the alveolar ridge, and provide sufficient bone for oral rehabilitation.

The aim of this Special Issue is to evaluate original research papers, reviews, and technical reports, encouraging manuscripts concerning the state of art in the fields of stem cell biology and molecules for the treatment of the bone defects.

Potential topics include but are not limited to the following:

  • Dental pulp stem cells for bone regeneration;
  • Applications of molecules for bone regeneration;
  • Stem cells seeded on scaffolds for tissue engineering;
  • Stem cells and blood-derived growth factors for hard and soft tissue healing;
  • Antioxidant protection against oxidative stress of new generation compounds on different mesenchymal cell lines;
  • Tissue engineering;
  • Bone regeneration;
  • Dental implants, biomaterials, and surface properties;
  • Stem cells as tools to test novel biomaterials for regenerative medicine.

Prof. Adriano Piatelli
Prof. Dr. Giovanna Iezzi
Dr. Natalia Di Pietro
Dr. Margherita Tumedei
Guest Editors

Manuscript Submission Information

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Keywords

  • Stem cells
  • Mesenchymal stem cells
  • Biomaterials
  • Tissue regeneration
  • Tissue engineering
  • Regenerative medicine
  • Implant surfaces
  • Bone regeneration
  • Osseointegration
  • Wound healing
  • Molecules

Published Papers (6 papers)

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Research

14 pages, 12255 KiB  
Article
Osseointegration Potential Assessment of Bone Graft Materials Loaded with Mesenchymal Stem Cells in Peri-Implant Bone Defects
Int. J. Mol. Sci. 2024, 25(2), 862; https://doi.org/10.3390/ijms25020862 - 10 Jan 2024
Viewed by 452
Abstract
Many studies have been exploring the use of bone graft materials (BGMs) and mesenchymal stem cells in bone defect reconstruction. However, the regeneration potential of Algipore (highly purified hydroxyapatite) and Biphasic (hydroxyapatite/beta-tricalcium phosphate) BGMs combined with bone marrow–derived mesenchymal stem cells (BMSCs) remains [...] Read more.
Many studies have been exploring the use of bone graft materials (BGMs) and mesenchymal stem cells in bone defect reconstruction. However, the regeneration potential of Algipore (highly purified hydroxyapatite) and Biphasic (hydroxyapatite/beta-tricalcium phosphate) BGMs combined with bone marrow–derived mesenchymal stem cells (BMSCs) remains unclear. Therefore, we evaluated their osseointegration capacities in reconstructing peri-implant bone defects. The cellular characteristics of BMSCs and the material properties of Algipore and Biphasic were assessed in vitro. Four experimental groups—Algipore, Biphasic, Algipore+BMSCs, and Biphasic+BMSCs—were designed in a rabbit tibia peri-implant defect model. Implant stability parameters were measured. After 4 and 8 weeks of healing, all samples were evaluated using micro-CT, histological, and histomorphometric analysis. In the energy-dispersive X-ray spectroscopy experiment, the Ca/P ratio was higher for Algipore (1.67) than for Biphasic (1.44). The ISQ values continuously increased, and the PTV values gradually decreased for all groups during the healing period. Both Algipore and Biphasic BGM promoted new bone regeneration. Higher implant stability and bone volume density were observed when Algipore and Biphasic BGMs were combined with BMSCs. Biphasic BGM exhibited a faster degradation rate than Algipore BGM. Notably, after eight weeks of healing, Algipore with BSMCs showed more bone–implant contact than Biphasic alone (p < 0.05). Both Algipore and Biphasic are efficient in reconstructing peri-implant bone defects. In addition, Algipore BGM incorporation with BSMCs displayed the best performance in enhancing implant stability and osseointegration potential. Full article
(This article belongs to the Special Issue The Molecules and Stem Cells in Bone Regeneration)
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15 pages, 4327 KiB  
Article
Osteoblasts and Fibroblasts Interaction with a Porcine Acellular Dermal Matrix Membrane
Int. J. Mol. Sci. 2023, 24(4), 3649; https://doi.org/10.3390/ijms24043649 - 11 Feb 2023
Cited by 2 | Viewed by 1190
Abstract
The use of collagen membranes has remained the gold standard in GTR/GBR. In this study, the features and the biological activities of an acellular porcine dermis collagen matrix membrane applicable during dental surgery were investigated, and also by applying hydration with NaCl. Thus, [...] Read more.
The use of collagen membranes has remained the gold standard in GTR/GBR. In this study, the features and the biological activities of an acellular porcine dermis collagen matrix membrane applicable during dental surgery were investigated, and also by applying hydration with NaCl. Thus, two tested membranes were distinguished, the H-Membrane and Membrane, compared to the control cell culture plastic. The characterization was performed by SEM and histological analyses. In contrast, the biocompatibility was investigated on HGF and HOB cells at 3, 7, and 14 days by MTT for proliferation study; by SEM and histology for cell interaction study; and by RT-PCR for function-related genes study. In HOBs seeded on membranes, mineralization functions by ALP assay and Alizarin Red staining were also investigated. Results indicated that the tested membranes, especially when hydrated, can promote the proliferation and attachment of cells at each time. Furthermore, membranes significantly increased ALP and mineralization activities in HOBs as well as the osteoblastic-related genes ALP and OCN. Similarly, membranes significantly increased ECM-related and MMP8 gene expression in HGFs. In conclusion, the tested acellular porcine dermis collagen matrix membrane, mainly when it is hydrated, behaved as a suitable microenvironment for oral cells. Full article
(This article belongs to the Special Issue The Molecules and Stem Cells in Bone Regeneration)
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16 pages, 3123 KiB  
Article
The Osteogenic Differentiation of Human Dental Pulp Stem Cells through G0/G1 Arrest and the p-ERK/Runx-2 Pathway by Sonic Vibration
Int. J. Mol. Sci. 2021, 22(18), 10167; https://doi.org/10.3390/ijms221810167 - 21 Sep 2021
Cited by 7 | Viewed by 2185
Abstract
Mechanical/physical stimulations modulate tissue metabolism, and this process involves multiple cellular mechanisms, including the secretion of growth factors and the activation of mechano-physically sensitive kinases. Cells and tissue can be modulated through specific vibration-induced changes in cell activity, which depend on the vibration [...] Read more.
Mechanical/physical stimulations modulate tissue metabolism, and this process involves multiple cellular mechanisms, including the secretion of growth factors and the activation of mechano-physically sensitive kinases. Cells and tissue can be modulated through specific vibration-induced changes in cell activity, which depend on the vibration frequency and occur via differential gene expression. However, there are few reports about the effects of medium-magnitude (1.12 g) sonic vibration on the osteogenic differentiation of human dental pulp stem cells (HDPSCs). In this study, we investigated whether medium-magnitude (1.12 g) sonic vibration with a frequency of 30, 45, or 100 Hz could affect the osteogenic differentiation of HDPSCs. Their cell morphology changed to a cuboidal shape at 45 Hz and 100 Hz, but the cells in the other groups were elongated. FACS analysis showed decreased CD 73, CD 90, and CD 105 expression at 45 Hz and 100 Hz. Additionally, the proportions of cells in the G0/G1 phase in the control, 30 Hz, 45 Hz, and 100 Hz groups after vibration were 60.7%, 65.9%, 68.3%, and 66.7%, respectively. The mRNA levels of osteogenic-specific markers, including osteonectin, osteocalcin, BMP-2, ALP, and Runx-2, increased at 45 and 100 Hz, and the ALP and calcium content was elevated in the vibration groups compared with those in the control. Additionally, the western blotting results showed that p-ERK, BSP, osteoprotegerin, and osteonectin proteins were upregulated at 45 Hz compared with the other groups. The vibration groups showed higher ALP and calcium content than the control. Vibration, especially at 100 Hz, increased the number of calcified nodes relative to the control group, as evidenced by von Kossa staining. Immunohistochemical staining demonstrated that type I and III collagen, osteonectin, and osteopontin were upregulated at 45 Hz and 100 Hz. These results suggest that medium magnitude vibration at 45 Hz induces the G0/G1 arrest of HDPSCs through the p-ERK/Runx-2 pathway and can serve as a potent stimulator of differentiation and extracellular matrix production. Full article
(This article belongs to the Special Issue The Molecules and Stem Cells in Bone Regeneration)
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13 pages, 3973 KiB  
Article
Influence of Nano, Micro, and Macro Topography of Dental Implant Surfaces on Human Gingival Fibroblasts
Int. J. Mol. Sci. 2021, 22(18), 9871; https://doi.org/10.3390/ijms22189871 - 13 Sep 2021
Cited by 16 | Viewed by 2452
Abstract
Current research on dental implants has mainly focused on the influence of surface roughness on the rate of osseointegration, while studies on the development of surfaces to also improve the interaction of peri-implant soft tissues are lacking. To this end, the first purpose [...] Read more.
Current research on dental implants has mainly focused on the influence of surface roughness on the rate of osseointegration, while studies on the development of surfaces to also improve the interaction of peri-implant soft tissues are lacking. To this end, the first purpose of this study was to evaluate the response of human gingival fibroblasts (hGDFs) to titanium implant discs (Implacil De Bortoli, Brazil) having different micro and nano-topography: machined (Ti-M) versus sandblasted/double-etched (Ti-S). The secondary aim was to investigate the effect of the macrogeometry of the discs on cells: linear-like (Ti-L) versus wave-like (Ti-W) surfaces. The atomic force microscopy (AFM) and scanning electron microscopy (SEM) analysis showed that the Ti-S surfaces were characterized by a significantly higher micro and nano roughness and showed the 3D macrotopography of Ti-L and Ti-W surfaces. For in vitro analyses, the hGDFs were seeded into titanium discs and analyzed at 1, 3, and 5 days for adhesion and morphology (SEM) viability and proliferation (Cck-8 and MTT assays). The results showed that all tested surfaces were not cytotoxic for the hGDFs, rather the nano-micro and macro topography favored their proliferation in a time-dependent manner. Especially, at 3 and 5 days, the number of cells on Ti-L was higher than on other surfaces, including Ti-W surfaces. In conclusion, although further studies are needed, our in vitro data proved that the use of implant discs with Ti-S surfaces promotes the adhesion and proliferation of gingival fibroblasts, suggesting their use for in vivo applications. Full article
(This article belongs to the Special Issue The Molecules and Stem Cells in Bone Regeneration)
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12 pages, 3306 KiB  
Article
Osseointegration of Sandblasted and Acid-Etched Implant Surfaces. A Histological and Histomorphometric Study in the Rabbit
Int. J. Mol. Sci. 2021, 22(16), 8507; https://doi.org/10.3390/ijms22168507 - 07 Aug 2021
Cited by 20 | Viewed by 2212
Abstract
Titanium surface is an important factor in achieving osseointegration during the early wound healing of dental implants in alveolar bone. The purpose of this study was to evaluate sandblasted-etched surface implants to investigate the osseointegration. In the present study, we used two different [...] Read more.
Titanium surface is an important factor in achieving osseointegration during the early wound healing of dental implants in alveolar bone. The purpose of this study was to evaluate sandblasted-etched surface implants to investigate the osseointegration. In the present study, we used two different types of sandblasted-etched surface implants, an SLA™ surface and a Nanoblast Plus™ surface. Roughness and chemical composition were evaluated by a white light interferometer microscope and X-ray photoelectron spectroscopy, respectively. The SLA™ surface exhibited the higher values (Ra 3.05 μm) of rugosity compared to the Nanoblast Plus™ surface (Ra 1.78 μm). Both types of implants were inserted in the femoral condyles of ten New Zealand white rabbits. After 12 weeks, histological and histomorphometric analysis was performed. All the implants were osseointegrated and no signs of infection were observed. Histomorphometric analysis revealed that the bone–implant contact % (BIC) ratio was similar around the SLA™ implants (63.74 ± 13.61) than around the Nanoblast Plus™ implants (62.83 ± 9.91). Both implant surfaces demonstrated a favorable bone response, confirming the relevance of the sandblasted-etched surface on implant osseointegration. Full article
(This article belongs to the Special Issue The Molecules and Stem Cells in Bone Regeneration)
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13 pages, 3406 KiB  
Article
Platelet-Rich Fibrin Increases BMP2 Expression in Oral Fibroblasts via Activation of TGF-β Signaling
Int. J. Mol. Sci. 2021, 22(15), 7935; https://doi.org/10.3390/ijms22157935 - 25 Jul 2021
Cited by 9 | Viewed by 2290
Abstract
Solid platelet-rich fibrin (PRF), consisting of coagulated plasma from fractionated blood, has been proposed to be a suitable carrier for recombinant bone morphogenetic protein 2 (BMP2) to target mesenchymal cells during bone regeneration. However, whether solid PRF can increase the expression of BMPs [...] Read more.
Solid platelet-rich fibrin (PRF), consisting of coagulated plasma from fractionated blood, has been proposed to be a suitable carrier for recombinant bone morphogenetic protein 2 (BMP2) to target mesenchymal cells during bone regeneration. However, whether solid PRF can increase the expression of BMPs in mesenchymal cells remains unknown. Proteomics analysis confirmed the presence of TGF-β1 but not BMP2 in PRF lysates. According to the existing knowledge of recombinant TGF-β1, we hypothesized that PRF can increase BMP2 expression in mesenchymal cells. To test this hypothesis, we blocked TGF-β receptor 1 kinase with SB431542 in gingival fibroblasts exposed to PRF lysates. RT-PCR and immunoassays confirmed that solid PRF lysates caused a robust SB431542-dependent increase in BMP2 expression in gingival fibroblasts. Additionally, fractions of liquid PRF, namely platelet-poor plasma (PPP) and the buffy coat (BC) layer, but not heat-denatured PPP (Alb-gel), greatly induced the expression of BMP2 in gingival fibroblasts. Even though PRF has no detectable BMPs, PRF lysates similar to recombinant TGF-β1 had the capacity to provoke canonical BMP signaling, as indicated by the nuclear translocation of Smad1/5 and the increase in its phosphorylation. Taken together, our data suggest that PRF can activate TGF-β receptor 1 kinase and consequently induce the production of BMP2 in cells of the mesenchymal lineage. Full article
(This article belongs to the Special Issue The Molecules and Stem Cells in Bone Regeneration)
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