Bone Regeneration and Repair Materials

A special issue of Journal of Functional Biomaterials (ISSN 2079-4983). This special issue belongs to the section "Bone Biomaterials".

Deadline for manuscript submissions: closed (20 February 2024) | Viewed by 28898

Special Issue Editors


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Guest Editor
Bone Research Lab, School of Dentistry of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil
Interests: bone biology; bone regeneration; cell culture; cell therapy; bone biomaterials; molecular biology

E-Mail Website
Guest Editor
Bone Research Lab, School of Dentistry of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil
Interests: bone; biomaterials; cell therapy; regenerative medicine; cell signalling

Special Issue Information

Dear Colleagues,

Bone tissue has a remarkable capacity to regenerate after injury and trauma. However, the extent of bone loss or the presence of concurring diseases can often surpass its regenerative ability, leading to the failure of conventional procedures and, consequently, the need for additional treatments. Regenerative medicine in the context of bone regeneration encompasses all currently available treatments including biological and material approaches as well as the combination of both, which are under the scrutiny of researchers and clinicians. This Special Issue, “Bone Regeneration and Repair Materials”, aims to compile original articles and reviews in this field, covering all aspects of scientific investigation from bench to bedside. Papers dealing with, but not limited to: new insights on the use of grafts and/or fixation devices; the role of cells and growth factors, either combined or not with biomaterials; the development, physico-chemical modifications, characterizations, and biological evaluations of bone biomaterials; and innovative advances toward bone regeneration are of great interest.

Prof. Dr. Adalberto Luiz Rosa
Prof. Dr. Marcio Mateus Beloti
Guest Editors

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Keywords

  • biomaterials
  • bone
  • graft
  • cell therapy
  • fixation devices
  • regenerative medicine
  • tissue engineering

Published Papers (17 papers)

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Editorial

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5 pages, 203 KiB  
Editorial
Bone Regeneration and Repair Materials
by Marcio Mateus Beloti and Adalberto Luiz Rosa
J. Funct. Biomater. 2024, 15(3), 78; https://doi.org/10.3390/jfb15030078 - 21 Mar 2024
Viewed by 623
Abstract
Bone tissue has a remarkable ability to regenerate following injury and trauma [...] Full article
(This article belongs to the Special Issue Bone Regeneration and Repair Materials)

Research

Jump to: Editorial, Review

13 pages, 3048 KiB  
Article
Estrogen Deficiency Impairs Osseointegration in Hypertensive Rats Even Treated with Alendronate Coated on the Implant Surface
by Gabriel Mulinari-Santos, Jaqueline Silva dos Santos, Igor Lebedenco Kitagawa, Fábio Roberto de Souza Batista, Paulo Roberto Botacin, Cristina Antoniali, Paulo Noronha Lisboa-Filho and Roberta Okamoto
J. Funct. Biomater. 2023, 14(9), 471; https://doi.org/10.3390/jfb14090471 - 13 Sep 2023
Cited by 1 | Viewed by 1002
Abstract
Hypertension and estrogen deficiency can affect bone metabolism and therefore increase the risk of osseointegration. Antihypertensive drugs such as losartan not only control blood pressure but also enhance bone healing. In addition, alendronate sodium is widely used to treat postmenopausal osteoporosis. Hence, we [...] Read more.
Hypertension and estrogen deficiency can affect bone metabolism and therefore increase the risk of osseointegration. Antihypertensive drugs such as losartan not only control blood pressure but also enhance bone healing. In addition, alendronate sodium is widely used to treat postmenopausal osteoporosis. Hence, we evaluated the effect of systemic antihypertensive and local alendronate coted on implants on osseointegration under hypertensive and estrogen-deficiency conditions. A total of 64 spontaneously hypertensive rats (SHRs) treated with losartan were randomly divided according to the estrogen-deficiency induction by ovariectomy (OVX) or not (SHAM), and whether the implant surface was coated with sodium alendronate (ALE) or not, resulting in four groups: SHR SHAM, SHR SHAM ALE, SHR OVX, and SHR OVX ALE. The removal torque, microcomputed tomography, and epifluorescence microscopy were the adopted analyses. The hypertensive and estrogen-deficiency animals presented a lower removal torque even when treated with alendronate on implant surface. The microcomputed tomography revealed a higher bone volume and bone-to-implant contact in the SHRs than the SHR OVX rats. Epifluorescence showed a decreased mineral apposition ratio in the SHR OVX ALE group. The data presented indicate that estrogen deficiency impairs osseointegration in hypertensive rats; in addition, alendronate coated on the implant surface does not fully reverse this impaired condition caused by estrogen deficiency. Full article
(This article belongs to the Special Issue Bone Regeneration and Repair Materials)
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17 pages, 3630 KiB  
Article
Biomimetic Nacre-like Hydroxyapatite/Polymer Composites for Bone Implants
by Parinaz Tabrizian, Huijun Sun, Urangua Jargalsaikhan, Tan Sui, Sean Davis and Bo Su
J. Funct. Biomater. 2023, 14(8), 393; https://doi.org/10.3390/jfb14080393 - 25 Jul 2023
Cited by 1 | Viewed by 1305
Abstract
One of the most ambitious goals for bone implants is to improve bioactivity, incapability, and mechanical properties; to reduce the need for further surgery; and increase efficiency. Hydroxyapatite (HA), the main inorganic component of bones and teeth, has high biocompatibility but is weak [...] Read more.
One of the most ambitious goals for bone implants is to improve bioactivity, incapability, and mechanical properties; to reduce the need for further surgery; and increase efficiency. Hydroxyapatite (HA), the main inorganic component of bones and teeth, has high biocompatibility but is weak and brittle material. Cortical bone is composed of 70% calcium phosphate (CaP) and 30% collagen and forms a complex hierarchical structure with anisotropic and lamellar microstructure (osteons) which makes bone a light, strong, tough, and durable material that can support large loads. However, imitation of concentric lamellar structure of osteons is difficult to achieve in fabrication. Nacre from mollusk shells with layered structures has now become the archetype of the natural “model” for bio-inspired materials. Incorporating a nacre-like layered structure into bone implants can enhance their mechanical strength, toughness, and durability, reducing the risk of implant catastrophic failure or fracture. The layered structure of nacre-like HA/polymer composites possess high strength, toughness, and tunable stiffness which matches that of bone. The nacre-like HA/polymer composites should also possess excellent biocompatibility and bioactivity which facilitate the bonding of the implant with the surrounding bone, leading to improved implant stability and long-term success. To achieve this, a bi-directional freeze-casting technique was used to produce elongated lamellar HA were further densified and infiltrated with polymer to produce nacre-like HA/polymer composites with high strength and fracture toughness. Mechanical characterization shows that increasing the ceramic fractions in the composite increases the density of the mineral bridges, resulting in higher flexural and compressive strength. The nacre-like HA/(methyl methacrylate (MMA) + 5 wt.% acrylic acid (AA)) composites with a ceramic fraction of 80 vol.% showed a flexural strength of 158 ± 7.02 MPa and a Young’s modulus of 24 ± 4.34 GPa, compared with 130 ± 5.82 MPa and 19.75 ± 2.38 GPa, in the composite of HA/PMMA, due to the higher strength of the polymer and the interface of the composite. The fracture toughness in the composition of 5 wt.% PAA to PMMA improves from 3.023 ± 0.98 MPa·m1/2 to 5.27 ± 1.033 MPa·m1/2 by increasing the ceramic fraction from 70 vol.% to 80 vol.%, respectively. Full article
(This article belongs to the Special Issue Bone Regeneration and Repair Materials)
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12 pages, 2423 KiB  
Article
Physicochemical Characterization of Thermally Processed Goose Bone Ash for Bone Regeneration
by Fatimah Suhaily Abdul Rahman, Abdul Manaf Abdullah, Asanah Radhi, Wan Nazatul Shima Shahidan and Johari Yap Abdullah
J. Funct. Biomater. 2023, 14(7), 351; https://doi.org/10.3390/jfb14070351 - 30 Jun 2023
Viewed by 1287
Abstract
Goose bone is traditionally applied for many ailments including bone fractures. Goose bone that consists of calcium phosphate plays a major role in bone regeneration. In this study, the production of goose bone ash (GBA) was translated from a traditional process into one [...] Read more.
Goose bone is traditionally applied for many ailments including bone fractures. Goose bone that consists of calcium phosphate plays a major role in bone regeneration. In this study, the production of goose bone ash (GBA) was translated from a traditional process into one of a laboratory scale via thermal and mechanical methods. The GBA was thermally processed via calcination at 300 °C and 900 °C. The differences in physicochemical properties between studied GBA (SGBA) and commercial GBA (CGBA) were elucidated via Fourier transform infrared (FT-IR), X-ray fluorescence (XRF), X-ray diffraction (XRD) and electron diffraction X-Ray (EDX). The morphological properties of SGBA and CGBA were characterized using field emission scanning electron microscopy (FESEM) in which nano-sized particles were detected. The results showed that the SGBA of 300 °C had comparable physicochemical properties to those of CGBA. A high processing temperature was associated with decreasing organic compounds and increasing crystallinity. The finding from EDX suggests that sintering at 900 °C (SGBA 900) demonstrated the presence of hydroxyapatite in the mineralogical phase and had a Ca/P atomic ratio of 1.64 which is comparable to the ideal stoichiometric ratio of 1.67. Findings from this study could be used for the further exploration of GBA as a potential material for bone regeneration via the elucidation of their biological properties in the next experimental setting. Full article
(This article belongs to the Special Issue Bone Regeneration and Repair Materials)
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13 pages, 5013 KiB  
Article
Mesenchymal Stem Cells Combined with a P(VDF-TrFE)/BaTiO3 Scaffold and Photobiomodulation Therapy Enhance Bone Repair in Rat Calvarial Defects
by Leticia Faustino Adolpho, Larissa Mayra Silva Ribeiro, Gileade Pereira Freitas, Helena Bacha Lopes, Maria Paula Oliveira Gomes, Emanuela Prado Ferraz, Rossano Gimenes, Marcio Mateus Beloti and Adalberto Luiz Rosa
J. Funct. Biomater. 2023, 14(6), 306; https://doi.org/10.3390/jfb14060306 - 01 Jun 2023
Viewed by 1747
Abstract
Background: Tissue engineering and cell therapy have been the focus of investigations on how to treat challenging bone defects. This study aimed to produce and characterize a P(VDF-TrFE)/BaTiO3 scaffold and evaluate the effect of mesenchymal stem cells (MSCs) combined with this scaffold [...] Read more.
Background: Tissue engineering and cell therapy have been the focus of investigations on how to treat challenging bone defects. This study aimed to produce and characterize a P(VDF-TrFE)/BaTiO3 scaffold and evaluate the effect of mesenchymal stem cells (MSCs) combined with this scaffold and photobiomodulation (PBM) on bone repair. Methods and results: P(VDF-TrFE)/BaTiO3 was synthesized using an electrospinning technique and presented physical and chemical properties suitable for bone tissue engineering. This scaffold was implanted in rat calvarial defects (unilateral, 5 mm in diameter) and, 2 weeks post-implantation, MSCs were locally injected into these defects (n = 12/group). Photobiomodulation was then applied immediately, and again 48 and 96 h post-injection. The μCT and histological analyses showed an increment in bone formation, which exhibited a positive correlation with the treatments combined with the scaffold, with MSCs and PBM inducing more bone repair, followed by the scaffold combined with PBM, the scaffold combined with MSCs, and finally the scaffold alone (ANOVA, p ≤ 0.05). Conclusions: The P(VDF-TrFE)/BaTiO3 scaffold acted synergistically with MSCs and PBM to induce bone repair in rat calvarial defects. These findings emphasize the need to combine a range of techniques to regenerate large bone defects and provide avenues for further investigations on innovative tissue engineering approaches. Full article
(This article belongs to the Special Issue Bone Regeneration and Repair Materials)
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12 pages, 6444 KiB  
Article
Laser-Modified Ti Surface Improves Paracrine Osteogenesis by Modulating the Expression of DKK1 in Osteoblasts
by Jorge Felipe Lima Teixeira, João Antônio Chaves de Souza, Fernando Augusto Cintra Magalhães, Guilherme José Pimentel Lopes de Oliveira, José Bernardo de Santis, Carlos Alberto de Souza Costa and Pedro Paulo Chaves de Souza
J. Funct. Biomater. 2023, 14(4), 224; https://doi.org/10.3390/jfb14040224 - 16 Apr 2023
Viewed by 1327
Abstract
Titanium surface modifications are widely used to modulate cellular behavior by recognition of topographical cues. However, how those modifications affect the expression of mediators that will influence neighboring cells is still elusive. This study aimed to evaluate the effects of conditioned media from [...] Read more.
Titanium surface modifications are widely used to modulate cellular behavior by recognition of topographical cues. However, how those modifications affect the expression of mediators that will influence neighboring cells is still elusive. This study aimed to evaluate the effects of conditioned media from osteoblasts cultured on laser-modified titanium surfaces on the differentiation of bone marrow cells in a paracrine manner and to analyze the expression of Wnt pathway inhibitors. Mice calvarial osteoblasts were seeded on polished (P) and Yb:YAG laser-irradiated (L) Ti surfaces. Osteoblast culture media were collected and filtered on alternate days to stimulate mice BMCs. Resazurin assay was performed every other day for 20 days to check BMC viability and proliferation. After 7 and 14 days of BMCs maintained with osteoblasts P and L-conditioned media, alkaline phosphatase activity, Alizarin Red staining, and RT-qPCR were performed. ELISA of conditioned media was conducted to investigate the expression of Wnt inhibitors Dickkopf-1 (DKK1) and Sclerostin (SOST). BMCs showed increased mineralized nodule formation and alkaline phosphatase activity. The L-conditioned media enhanced the BMC mRNA expression of bone-related markers Bglap, Alpl, and Sp7. L-conditioned media decreased the expression of DKK1 compared with P-conditioned media. The contact of osteoblasts with Yb:YAG laser-modified Ti surfaces induces the regulation of the expression of mediators that affect the osteoblastic differentiation of neighboring cells. DKK1 is among these regulated mediators. Full article
(This article belongs to the Special Issue Bone Regeneration and Repair Materials)
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16 pages, 3456 KiB  
Article
Adipogenesis-Related Metabolic Condition Affects Shear-Stressed Endothelial Cells Activity Responding to Titanium
by Thaís Silva Pinto, Anderson Moreira Gomes, Paula Bertin de Morais and Willian F. Zambuzzi
J. Funct. Biomater. 2023, 14(3), 162; https://doi.org/10.3390/jfb14030162 - 17 Mar 2023
Viewed by 1409
Abstract
Purpose: Obesity has increased around the world. Obese individuals need to be better assisted, with special attention given to dental and medical specialties. Among obesity-related complications, the osseointegration of dental implants has raised concerns. This mechanism depends on healthy angiogenesis surrounding the implanted [...] Read more.
Purpose: Obesity has increased around the world. Obese individuals need to be better assisted, with special attention given to dental and medical specialties. Among obesity-related complications, the osseointegration of dental implants has raised concerns. This mechanism depends on healthy angiogenesis surrounding the implanted devices. As an experimental analysis able to mimic this issue is currently lacking, we address this issue by proposing an in vitro high-adipogenesis model using differentiated adipocytes to further investigate their endocrine and synergic effect in endothelial cells responding to titanium. Materials and methods: Firstly, adipocytes (3T3-L1 cell line) were differentiated under two experimental conditions: Ctrl (normal glucose concentration) and High-Glucose Medium (50 mM of glucose), which was validated using Oil Red O Staining and inflammatory markers gene expression by qPCR. Further, the adipocyte-conditioned medium was enriched by two types of titanium-related surfaces: Dual Acid-Etching (DAE) and Nano-Hydroxyapatite blasted surfaces (nHA) for up to 24 h. Finally, the endothelial cells (ECs) were exposed in those conditioned media under shear stress mimicking blood flow. Important genes related to angiogenesis were then evaluated by using RT-qPCR and Western blot. Results: Firstly, the high-adipogenicity model using 3T3-L1 adipocytes was validated presenting an increase in the oxidative stress markers, concomitantly with an increase in intracellular fat droplets, pro-inflammatory-related gene expressions, and also the ECM remodeling, as well as modulating mitogen-activated protein kinases (MAPKs). Additionally, Src was evaluated by Western blot, and its modulation can be related to EC survival signaling. Conclusion: Our study provides an experimental model of high adipogenesis in vitro by establishing a pro-inflammatory environment and intracellular fat droplets. Additionally, the efficacy of this model to evaluate the EC response to titanium-enriched mediums under adipogenicity-related metabolic conditions was analyzed, revealing significant interference with EC performance. Altogether, these data gather valuable findings on understanding the reasons for the higher percentage of implant failures in obese individuals. Full article
(This article belongs to the Special Issue Bone Regeneration and Repair Materials)
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19 pages, 4808 KiB  
Article
Different Species of Marine Sponges Diverge in Osteogenic Potential When Therapeutically Applied as Natural Scaffolds for Bone Regeneration in Rats
by Cíntia P. G. Santos, João P. S. Prado, Kelly R. Fernandes, Hueliton W. Kido, Bianca P. Dorileo, Julia R. Parisi, Jonas A. Silva, Matheus A. Cruz, Márcio R. Custódio, Ana C. M. Rennó and Renata N. Granito
J. Funct. Biomater. 2023, 14(3), 122; https://doi.org/10.3390/jfb14030122 - 24 Feb 2023
Cited by 3 | Viewed by 1676
Abstract
A highly porous structure, and an inorganic (biosilica) and collagen-like organic content (spongin) makes marine sponges potential candidates to be used as natural scaffolds in bone tissue engineering. The aim of this study was to characterize (through SEM, FTIR, EDS, XRD, pH, mass [...] Read more.
A highly porous structure, and an inorganic (biosilica) and collagen-like organic content (spongin) makes marine sponges potential candidates to be used as natural scaffolds in bone tissue engineering. The aim of this study was to characterize (through SEM, FTIR, EDS, XRD, pH, mass degradation and porosity tests) scaffolds produced from two species of marine sponges, Dragmacidon reticulatum (DR) and Amphimedon viridis (AV), and to evaluate the osteogenic potential of these scaffolds by using a bone defect model in rats. First, it was shown that the same chemical composition and porosity (84 ± 5% for DR and 90 ± 2% for AV) occurs among scaffolds from the two species. Higher material degradation was observed in the scaffolds of the DR group, with a greater loss of organic matter after incubation. Later, scaffolds from both species were surgically introduced in rat tibial defects, and histopathological analysis after 15 days showed the presence of neo-formed bone and osteoid tissue within the bone defect in DR, always around the silica spicules. In turn, AV exhibited a fibrous capsule around the lesion (19.9 ± 17.1%), no formation of bone tissue and only a small amount of osteoid tissue. The results showed that scaffolds manufactured from Dragmacidon reticulatum presented a more suitable structure for stimulation of osteoid tissue formation when compared to Amphimedon viridis marine sponge species. Full article
(This article belongs to the Special Issue Bone Regeneration and Repair Materials)
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15 pages, 15642 KiB  
Article
3D-Printed GelMA/PEGDA/F127DA Scaffolds for Bone Regeneration
by Jianpeng Gao, Ming Li, Junyao Cheng, Xiao Liu, Zhongyang Liu, Jianheng Liu and Peifu Tang
J. Funct. Biomater. 2023, 14(2), 96; https://doi.org/10.3390/jfb14020096 - 09 Feb 2023
Cited by 8 | Viewed by 2987
Abstract
Tissue-engineered scaffolds are an effective method for the treatment of bone defects, and their structure and function are essential for bone regeneration. Digital light processing (DLP) printing technology has been widely used in bone tissue engineering (BTE) due to its high printing resolution [...] Read more.
Tissue-engineered scaffolds are an effective method for the treatment of bone defects, and their structure and function are essential for bone regeneration. Digital light processing (DLP) printing technology has been widely used in bone tissue engineering (BTE) due to its high printing resolution and gentle printing process. As commonly used bioinks, synthetic polymers such as polyethylene glycol diacrylate (PEGDA) and Pluronic F127 diacrylate (F127DA) have satisfactory printability and mechanical properties but usually lack sufficient adhesion to cells and tissues. Here, a compound BTE scaffold based on PEGDA, F127DA, and gelatin methacrylate (GelMA) was successfully prepared using DLP printing technology. The scaffold not only facilitated the adhesion and proliferation of cells, but also effectively promoted the osteogenic differentiation of mesenchymal stem cells in an osteoinductive environment. Moreover, the bone tissue volume/total tissue volume (BV/TV) of the GelMA/PEGDA/F127DA (GPF) scaffold in vivo was 49.75 ± 8.50%, higher than the value of 37.10 ± 7.27% for the PEGDA/F127DA (PF) scaffold and 20.43 ± 2.08% for the blank group. Therefore, the GPF scaffold prepared using DLP printing technology provides a new approach to the treatment of bone defects. Full article
(This article belongs to the Special Issue Bone Regeneration and Repair Materials)
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27 pages, 7113 KiB  
Article
The Local Release of Teriparatide Incorporated in 45S5 Bioglass Promotes a Beneficial Effect on Osteogenic Cells and Bone Repair in Calvarial Defects in Ovariectomized Rats
by Juliani Caroline Ribeiro de Araújo, Leonardo Alvares Sobral Silva, Vinicius Almeida de Barros Lima, Tiago Moreira Bastos Campos, Paulo Noronha Lisboa Filho, Roberta Okamoto and Luana Marotta Reis de Vasconcellos
J. Funct. Biomater. 2023, 14(2), 93; https://doi.org/10.3390/jfb14020093 - 09 Feb 2023
Cited by 1 | Viewed by 1528
Abstract
With the increase in the population’s life expectancy, there has also been an increase in the rate of osteoporosis, which has expanded the search for strategies to regenerate bone tissue. The ultrasonic sonochemical technique was chosen for the functionalization of the 45S5 bioglass. [...] Read more.
With the increase in the population’s life expectancy, there has also been an increase in the rate of osteoporosis, which has expanded the search for strategies to regenerate bone tissue. The ultrasonic sonochemical technique was chosen for the functionalization of the 45S5 bioglass. The samples after the sonochemical process were divided into (a) functionalized bioglass (BG) and (b) functionalized bioglass with 10% teriparatide (BGT). Isolated mesenchymal cells (hMSC) from femurs of ovariectomized rats were differentiated into osteoblasts and submitted to in vitro tests. Bilateral ovariectomy (OVX) and sham ovariectomy (Sham) surgeries were performed in fifty-five female Wistar rats. After a period of 60 days, critical bone defects of 5.0 mm were created in the calvaria of these animals. For biomechanical evaluation, critical bone defects of 3.0 mm were performed in the tibias of some of these rats. The groups were divided into the clot (control) group, the BG group, and the BGT group. After the sonochemical process, the samples showed modified chemical topographic and morphological characteristics, indicating that the surface was chemically altered by the functionalization of the particles. The cell environment was conducive to cell adhesion and differentiation, and the BG and BGT groups did not show cytotoxicity. In addition, the experimental groups exhibited characteristics of new bone formation with the presence of bone tissue in both periods, with the BGT group and the OVX group statistically differing from the other groups (p < 0.05) in both periods. Local treatment with the drug teriparatide in ovariectomized animals promoted positive effects on bone tissue, and longitudinal studies should be carried out to provide additional information on the biological performance of the mutual action between the bioglass and the release of the drug teriparatide. Full article
(This article belongs to the Special Issue Bone Regeneration and Repair Materials)
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20 pages, 3756 KiB  
Article
Effects of Modulation of the Hedgehog and Notch Signaling Pathways on Osteoblast Differentiation Induced by Titanium with Nanotopography
by Paola Gomes Souza, Leticia Faustino Adolpho, Helena Bacha Lopes, Denise Weffort, Alann Thaffarell Portilho Souza, Fabiola Singaretti Oliveira, Adalberto Luiz Rosa and Marcio Mateus Beloti
J. Funct. Biomater. 2023, 14(2), 79; https://doi.org/10.3390/jfb14020079 - 30 Jan 2023
Cited by 4 | Viewed by 1572
Abstract
Background: The events of bone formation and osteoblast/titanium (Ti) interactions may be affected by Hedgehog and Notch signalling pathways. Herein, we investigated the effects of modulation of these signalling pathways on osteoblast differentiation caused by the nanostructured Ti (Ti-Nano) generated by H2 [...] Read more.
Background: The events of bone formation and osteoblast/titanium (Ti) interactions may be affected by Hedgehog and Notch signalling pathways. Herein, we investigated the effects of modulation of these signalling pathways on osteoblast differentiation caused by the nanostructured Ti (Ti-Nano) generated by H2SO4/H2O2. Methods: Osteoblasts from newborn rat calvariae were cultured on Ti-Control and Ti-Nano in the presence of the Hedgehog agonist purmorphamine or antagonist cyclopamine and of the Notch antagonist N-(3,5-Difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT) or agonist bexarotene. Osteoblast differentiation was evaluated by alkaline phosphatase activity and mineralization, and the expression of Hedgehog and Notch receptors was also evaluated. Results: In general, purmorphamine and DAPT increased while cyclopamine and bexarotene decreased osteoblast differentiation and regulated the receptor expression on both Ti surfaces, with more prominent effects on Ti-Nano. The purmorphamine and DAPT combination exhibited synergistic effects on osteoblast differentiation that was more intense on Ti-Nano. Conclusion: Our results indicated that the Hedgehog and Notch signalling pathways drive osteoblast/Ti interactions more intensely on nanotopography. We also demonstrated that combining Hedgehog activation with Notch inhibition exhibits synergistic effects on osteoblast differentiation, especially on Ti-Nano. The uncovering of these cellular mechanisms contributes to create strategies to control the process of osseointegration based on the development of nanostructured surfaces. Full article
(This article belongs to the Special Issue Bone Regeneration and Repair Materials)
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17 pages, 3976 KiB  
Article
Healing Patterns of Non-Collagenated Bovine and Collagenated Porcine Xenografts Used for Sinus Floor Elevation: A Histological Study in Rabbits
by Yuhei Miyauchi, Takayuki Izutani, Yuki Teranishi, Takahisa Iida, Yasushi Nakajima, Samuel Porfirio Xavier and Shunsuke Baba
J. Funct. Biomater. 2022, 13(4), 276; https://doi.org/10.3390/jfb13040276 - 05 Dec 2022
Cited by 5 | Viewed by 1238
Abstract
Objective: To compare healing of collagenated and non-collagenated xenografts used for maxillary sinus floor elevation. Materials and Methods: Two different xenografts were used: deproteinized bovine bone (DBBM group) and collagenated corticocancellous porcine bone (collagenated group). Healing was studied after 2, 4, and 8 [...] Read more.
Objective: To compare healing of collagenated and non-collagenated xenografts used for maxillary sinus floor elevation. Materials and Methods: Two different xenografts were used: deproteinized bovine bone (DBBM group) and collagenated corticocancellous porcine bone (collagenated group). Healing was studied after 2, 4, and 8 weeks. The loss of dimensions of the elevated area and the percentages of new bone, xenograft remnants, osteoclastic zones, vessels, inflammatory infiltrates, and soft tissues were analyzed. Three regions were evaluated: close to the bone walls (bone wall region), subjacent the sinus mucosa (submucosa region), and the center of the elevated area (middle region). The primary variables were the percentage of new bone and xenograft remnants. Results: Between 2 and 8 weeks, the elevated areas showed a reduction of 16.3% and 52.2% in the DBBM and collagenated groups, respectively (p < 0.01 between the two areas after 8 weeks). After 8 weeks, the highest content of new bone was observed in the bone wall region, which was higher in the collagenated group than in the DBBM group (41.6% and 28.6%, respectively; p < 0.01). A similar quantity of new bone was found between the two groups in other regions. A higher percentage of vessels in all regions evaluated (p < 0.01) and soft tissue in the sub-mucosa region (p < 0.05) was found in the collagenated group than in the DBBM group. Conclusions: The present study showed that both xenografts allowed new bone formation. In comparison with the non-collagenated xenograft, the collagenated xenograft underwent higher resorption, resulting in greater shrinkage of the elevated space after sinus lifting and a higher content of new bone in the regions close to the bone walls. Clinical relevance: In this study, the region adjacent to the bone wall showed the highest new bone content. This region resembles the base of the sinus, closest to the sinus floor and walls, and is the most important region from a clinical point of view because it is where the implant will be installed. Residues of the biomaterial remained after 8 weeks of healing. Other reports have shown that these biomaterial residues may interfere with the integration of implants. Full article
(This article belongs to the Special Issue Bone Regeneration and Repair Materials)
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10 pages, 2981 KiB  
Article
Sinus Mucosal Damage Triggered by Synthetic or Xenogeneic Bone Substitutes: A Histological Analysis in Rabbits
by Yuki Omori, Daniele Botticelli, Stefano Migani, Vitor Ferreira Balan, Eduardo Pires Godoy and Samuel Porfirio Xavier
J. Funct. Biomater. 2022, 13(4), 257; https://doi.org/10.3390/jfb13040257 - 19 Nov 2022
Cited by 2 | Viewed by 1537
Abstract
Background: It has been shown in rabbit models that the sinus mucosa in contact with graft particles might experience a progressive thinning and perforations. The phenomenon depends on the graft used. Hence, the aim of the present study was to compare the damaging [...] Read more.
Background: It has been shown in rabbit models that the sinus mucosa in contact with graft particles might experience a progressive thinning and perforations. The phenomenon depends on the graft used. Hence, the aim of the present study was to compare the damaging effects of a synthetic of a xenogeneic graft. Methods: Forty New Zealand rabbits received a bilateral sinus elevation. Both sinuses of twenty rabbits were grafted with a biphasic 60% hydroxyapatite and 40% β-tricalcium phosphate while the other twenty received a deproteinized bovine bone mineral graft. Thinned sites (<40 µm) and perforations on the mucosa in contact with graft particles were evaluated after 2 and 10 weeks (ten animals each period). The width of the pseudostratified epithelium was also measured as control. Results: After 2 weeks of healing, 61 thinned sites were detected in the Synthetic group and 49 in the Xenogeneic group. After 10 weeks, the number of thinned mucosae increased to 79 sites in the Synthetic group (p = 0.222 between periods), and to 114 sites in the Xenogeneic group (p = 0.030 between groups; p = 0.001 between periods). Perforations were few in the 2-week period, two in two sinuses out of 20 in the Synthetic group, and four in two sinuses out of 20 in the Xenogeneic group (p = 0.721). In the 10-week period, the perforations increased to eight in the Synthetic group, distributed in six sinuses out of 20, and to sixteen in the Xenogeneic group, distributed in 11 sinuses out of 20 (p = 0.082). The pseudostratified epithelium presented a reduced width at the thinned sites. Conclusions: The contact with synthetic or xenogeneic grafts will induce thinning and possible perforations of the sinus mucosa. This effect will increase over time, and it is stronger at the xenogeneic than the synthetic graft. Full article
(This article belongs to the Special Issue Bone Regeneration and Repair Materials)
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22 pages, 6627 KiB  
Article
Strontium Carbonate and Strontium-Substituted Calcium Carbonate Nanoparticles Form Protective Deposits on Dentin Surface and Enhance Human Dental Pulp Stem Cells Mineralization
by Tatiane Cristina Dotta, Larwsk Hayann, Leonardo de Padua Andrade Almeida, Lucas Fabrício B. Nogueira, Mayara M. Arnez, Raisa Castelo, Ana Flávia B. Cassiano, Gisele Faria, Milena Martelli-Tosi, Massimo Bottini, Pietro Ciancaglini, Alma B. C. E. B. Catirse and Ana Paula Ramos
J. Funct. Biomater. 2022, 13(4), 250; https://doi.org/10.3390/jfb13040250 - 17 Nov 2022
Cited by 4 | Viewed by 2415
Abstract
Strontium acetate is applied for dental hypersensitivity treatment; however, the use of strontium carbonates for this purpose has not been described. The use of Sr-carbonate nanoparticles takes advantage of both the benefits of strontium on dentin mineralization and the abrasive properties of carbonates. [...] Read more.
Strontium acetate is applied for dental hypersensitivity treatment; however, the use of strontium carbonates for this purpose has not been described. The use of Sr-carbonate nanoparticles takes advantage of both the benefits of strontium on dentin mineralization and the abrasive properties of carbonates. Here in, we aimed to synthesize strontium carbonate and strontium-substituted calcium carbonate nanoparticles and test them as potential compounds in active dentifrices for treating dental hypersensitivity. For this, SrCO3, Sr0.5Ca0.5CO3, and CaCO3 nanoparticles were precipitated using Na2CO3, SrCl2, and/or CaCl2 as precursors. Their morphology and crystallinity were evaluated by electron microscopy (SEM) and X-ray diffraction, respectively. The nanoparticles were added to a poly (vinyl alcohol) gel and used to brush dentin surfaces isolated from human third molars. Dentin chemical composition before and after brushing was investigated by infrared spectroscopy (FTIR) and X-ray dispersive energy spectroscopy. Dentin tubule morphology, obliteration, and resistance of the coatings to acid attack were investigated by SEM and EDS. The cytotoxicity and ability of the particles to trigger the mineralization of hDPSCs in vitro were studied. Dentin brushed with the nanoparticles was coated by a mineral layer that was also able to penetrate the tubules, while CaCO3 remained as individual particles on the surface. FTIR bands related to carbonate groups were intensified after brushing with either SrCO3 or Sr0.5Ca0.5CO3. The shift of the phosphate-related FTIR band to a lower wavenumber indicated that strontium replaced calcium on the dentin structure after treatment. The coating promoted by SrCO3 or Sr0.5Ca0.5CO3 resisted the acid attack, while calcium and phosphorus were removed from the top of the dentin surface. The nanoparticles were not toxic to hDPSCs and elicited mineralization of the cells, as revealed by increased mineral nodule formation and enhanced expression of COL1, ALP, and RUNX2. Adding Sr0.5Ca0.5CO3 as an active ingredient in dentifrices formulations may be commercially advantageous since this compound combines the well-known abrasive properties of calcium carbonate with the mineralization ability of strontium, while the final cost remains between the cost of CaCO3 and SrCO3. The novel Sr0.5Ca0.5CO3 nanoparticles might emerge as an alternative for the treatment of dental hypersensitivity. Full article
(This article belongs to the Special Issue Bone Regeneration and Repair Materials)
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14 pages, 2892 KiB  
Article
Hydrothermal Synthesis of Fluorapatite Coatings over Titanium Implants for Enhanced Osseointegration—An In Vivo Study in the Rabbit
by Eduardo Santiago, Victor Martin, Bruno Colaço, Maria Helena Fernandes, Catarina Santos and Pedro S. Gomes
J. Funct. Biomater. 2022, 13(4), 241; https://doi.org/10.3390/jfb13040241 - 14 Nov 2022
Cited by 6 | Viewed by 1537
Abstract
This work aims at the development and characterization of fluorapatite coatings, innovatively prepared by the hydrothermal method, aiming for enhanced osseointegration of titanium implants. Fluoride-containing coatings were prepared and characterized by scanning and transmission electron microscopy, Fourier-transform infrared spectroscopy—attenuated total reflectance, and X-ray [...] Read more.
This work aims at the development and characterization of fluorapatite coatings, innovatively prepared by the hydrothermal method, aiming for enhanced osseointegration of titanium implants. Fluoride-containing coatings were prepared and characterized by scanning and transmission electron microscopy, Fourier-transform infrared spectroscopy—attenuated total reflectance, and X-ray photoelectron spectroscopy. The biological response was characterized by microtomographic evaluation and histomorphometric analysis upon orthotopic implantation in a translational rabbit experimental model. Physic-chemical analysis revealed the inclusion of fluoride in the apatite lattice with fluorapatite formation, associated with the presence of citrate species. The in vivo biological assessment of coated implants revealed an enhanced bone formation process—with increased bone-to-implant contact and bone volume. The attained enhancement of the osteogenic process may be attributable to the conjoined modulatory activity of selected fluoride and citrate levels within the produced coatings. In this regard, the production of fluorapatite coatings with citrate, through the hydrothermal method, entails a promising approach for enhanced osseointegration in implant dentistry and orthopedic applications. Full article
(This article belongs to the Special Issue Bone Regeneration and Repair Materials)
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Review

Jump to: Editorial, Research

19 pages, 1359 KiB  
Review
Wood as Possible Renewable Material for Bone Implants—Literature Review
by Vadims Nefjodovs, Laura Andze, Martins Andzs, Inese Filipova, Ramunas Tupciauskas, Linda Vecbiskena and Martins Kapickis
J. Funct. Biomater. 2023, 14(5), 266; https://doi.org/10.3390/jfb14050266 - 10 May 2023
Cited by 2 | Viewed by 2866
Abstract
Bone fractures and bone defects affect millions of people every year. Metal implants for bone fracture fixation and autologous bone for defect reconstruction are used extensively in treatment of these pathologies. Simultaneously, alternative, sustainable, and biocompatible materials are being researched to improve existing [...] Read more.
Bone fractures and bone defects affect millions of people every year. Metal implants for bone fracture fixation and autologous bone for defect reconstruction are used extensively in treatment of these pathologies. Simultaneously, alternative, sustainable, and biocompatible materials are being researched to improve existing practice. Wood as a biomaterial for bone repair has not been considered until the last 50 years. Even nowadays there is not much research on solid wood as a biomaterial in bone implants. A few species of wood have been investigated. Different techniques of wood preparation have been proposed. Simple pre-treatments such as boiling in water or preheating of ash, birch and juniper woods have been used initially. Later researchers have tried using carbonized wood and wood derived cellulose scaffold. Manufacturing implants from carbonized wood and cellulose requires more extensive wood processing—heat above 800 °C and chemicals to extract cellulose. Carbonized wood and cellulose scaffolds can be combined with other materials, such as silicon carbide, hydroxyapatite, and bioactive glass to improve biocompatibility and mechanical durability. Throughout the publications wood implants have provided good biocompatibility and osteoconductivity thanks to wood’s porous structure. Full article
(This article belongs to the Special Issue Bone Regeneration and Repair Materials)
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18 pages, 4251 KiB  
Review
Global Trends and Future Research Directions for Temporomandibular Disorders and Stem Cells
by Zuleni Alexandre da Silva, Wallacy Watson Pereira Melo, Hadassa Helez Neves Ferreira, Rafael Rodrigues Lima and Renata Duarte Souza-Rodrigues
J. Funct. Biomater. 2023, 14(2), 103; https://doi.org/10.3390/jfb14020103 - 13 Feb 2023
Cited by 2 | Viewed by 1690
Abstract
Temporomandibular disorder (TMD) is an umbrella term used to describe various conditions that affect temporomandibular joints, masticatory muscles, and associated structures. Although the most conservative and least invasive treatment is preferable, more invasive therapies should be employed to refractory patients. Tissue engineering has [...] Read more.
Temporomandibular disorder (TMD) is an umbrella term used to describe various conditions that affect temporomandibular joints, masticatory muscles, and associated structures. Although the most conservative and least invasive treatment is preferable, more invasive therapies should be employed to refractory patients. Tissue engineering has been presented as a promising therapy. Our study aimed to investigate trends and point out future research directions on TMD and stem cells. A comprehensive search was carried out in the Web of Science Core Collection (WoS-CC) in October 2022. The bibliometric parameters were analyzed through descriptive statistics and graphical mapping. Thus, 125 papers, published between 1992 and 2022 in 65 journals, were selected. The period with the highest number of publications and citations was between 2012 and 2022. China has produced the most publications on the subject. The most frequently used keywords were “cartilage”, “temporomandibular joint”, “mesenchymal stem cells”, and “osteoarthritis”. Moreover, the primary type of study was in vivo. It was noticed that using stem cells to improve temporomandibular joint repair and regeneration is a significant subject of investigation. Nonetheless, a greater understanding of the biological interaction and the benefits of using these cells in patients with TMD is required. Full article
(This article belongs to the Special Issue Bone Regeneration and Repair Materials)
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