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1.
J Dent ; 145: 105033, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38697505

ABSTRACT

OBJECTIVES: This study aimed to enhance gingival fibroblast function and to achieve antibacterial activity around the implant abutment by using a zinc (Zn)-containing bioactive glass (BG) coating. METHODS: 45S5 BG containing 0, 5, and 10 wt.% Zn were coated on zirconia disks. The release of silica and Zn ions in physiological saline and their antibacterial effects were measured. The effects of BG coatings on human gingival fibroblasts (hGFs) were assessed using cytotoxicity assays and by analyzing the gene expression of various genes related to antioxidant enzymes, wound healing, and fibrosis. RESULTS: BG coatings are capable of continuous degradation and simultaneous ion release. The antibacterial effect of BG coatings increased with the addition of Zn, while the cytotoxicity remained unchanged compared to the group without coatings. BG coating enhances the expression of angiogenesis genes, while the Zn-containing BG enhances the expression of antioxidant genes at an early time point. BG coating enhances the expression of collagen genes at later time points. CONCLUSIONS: The antibacterial effect of BG improved with the increase in Zn concentration, without inducing cytotoxicity. BG coating enhances the expression of angiogenesis genes, and Zn-containing BG enhances the expression of antioxidant genes at an early time point. BG coating enhances the expression of collagen genes at later time points. CLINICAL SIGNIFICANCE: Adding 10 wt% Zn to BG could enhance the environment around implant abutments by providing antibacterial, antioxidant, and anti-fibrotic effects, having potential for clinical use.


Subject(s)
Anti-Bacterial Agents , Ceramics , Dental Abutments , Fibroblasts , Gingiva , Glass , Surface Properties , Zinc , Zirconium , Zirconium/pharmacology , Zirconium/chemistry , Humans , Zinc/pharmacology , Fibroblasts/drug effects , Anti-Bacterial Agents/pharmacology , Gingiva/cytology , Gingiva/drug effects , Glass/chemistry , Ceramics/pharmacology , Ceramics/chemistry , Coated Materials, Biocompatible/pharmacology , Coated Materials, Biocompatible/chemistry , Antioxidants/pharmacology , Materials Testing , Collagen , Wound Healing/drug effects , Dental Materials/pharmacology , Dental Materials/chemistry , Cells, Cultured
2.
Acta Biomater ; 180: 104-114, 2024 May.
Article in English | MEDLINE | ID: mdl-38583750

ABSTRACT

In the field of orthopedic surgery, there is an increasing need for the development of bone replacement materials for the treatment of bone defects. One of the main focuses of biomaterials engineering are advanced bioceramics like mesoporous bioactive glasses (MBG´s). The present study compared the new bone formation after 12 weeks of implantation of MBG scaffolds with composition 82,5SiO2-10CaO-5P2O5-x 2.5SrO alone (MBGA), enriched with osteostatin, an osteoinductive peptide, (MBGO) or enriched with bone marrow aspirate (MBGB) in a long bone critical defect in radius bone of adult New Zealand rabbits. New bone formation from the MBG scaffold groups was compared to the gold standard defect filled with iliac crest autograft and to the unfilled defect. Radiographic follow-up was performed at 2, 6, and 12 weeks, and microCT and histologic examination were performed at 12 weeks. X-Ray study showed the highest bone formation scores in the group with the defect filled with autograft, followed by the MBGB group, in addition, the microCT study showed that bone within defect scores (BV/TV) were higher in the MBGO group. This difference could be explained by the higher density of newly formed bone in the osteostatin enriched MBG scaffold group. Therefore, MBG scaffold alone and enriched with osteostatin or bone marrow aspirate increase bone formation compared to defect unfilled, being higher in the osteostatin group. The present results showed the potential to treat critical bone defects by combining MBGs with osteogenic peptides such as osteostatin, with good prospects for translation into clinical practice. STATEMENT OF SIGNIFICANCE: Treatment of bone defects without the capacity for self-repair is a global problem in the field of Orthopedic Surgery, as evidenced by the fact that in the U.S alone it affects approximately 100,000 patients per year. The gold standard of treatment in these cases is the autograft, but its use has limitations both in the amount of graft to be obtained and in the morbidity produced in the donor site. In the field of materials engineering, there is a growing interest in the development of a bone substitute equivalent. Mesoporous bioactive glass (MBG´s) scaffolds with three-dimensional architecture have shown great potential for use as a bone substitutes. The osteostatin-enriched Sr-MBG used in this long bone defect in rabbit radius bone in vivo study showed an increase in bone formation close to autograft, which makes us think that it may be an option to consider as bone substitute.


Subject(s)
Bone Substitutes , Glass , Tissue Scaffolds , Animals , Rabbits , Bone Substitutes/chemistry , Bone Substitutes/pharmacology , Tissue Scaffolds/chemistry , Glass/chemistry , Porosity , Diaphyses/pathology , Diaphyses/diagnostic imaging , Diaphyses/drug effects , X-Ray Microtomography , Osteogenesis/drug effects , Ceramics/chemistry , Ceramics/pharmacology , Male , Parathyroid Hormone-Related Protein/pharmacology , Bone Regeneration/drug effects , Peptide Fragments
3.
J Mater Chem B ; 12(14): 3494-3508, 2024 Apr 03.
Article in English | MEDLINE | ID: mdl-38512116

ABSTRACT

Magnetite (Fe3O4) nanoparticle (MNP)-substituted glass-ceramic (MSGC) powders with compositions of (45 - x)SiO2-24.5CaO-24.5Na2O-6P2O5-xFe3O4 (x = 5, 8, and 10 wt%) have been prepared by a sol-gel route by introducing Fe3O4 nanoparticles during the synthesis. The X-ray diffraction patterns of the as-prepared MSGC nanopowders revealed the presence of combeite (Na2Ca2Si3O9), magnetite, and sodium nitrate (NaNO3) crystalline phases. Heat-treatment up to 700 °C for 1 h resulted in the complete dissolution of NaNO3 along with partial conversion of magnetite into hematite (α-Fe2O3). Optimal heat-treatment of the MSGC powders at 550 °C for 1 h yielded the highest relative percentage of magnetite (without hematite) with some residual NaNO3. The saturation magnetization and heat generation capacity of the MSGC fluids increased with an increase in the MNP content. The in vitro bioactivity of the MSGC pellets was evaluated by monitoring the pH and the formation of a hydroxyapatite surface layer upon immersion in modified simulated body fluid. Proliferation of MG-63 osteoblast cells indicated that all of the MSGC compositions were non-toxic and MSGC with 10 wt% MNPs exhibited extraordinarily high cell viability. The MSGC with 10 wt% MNPs demonstrated optimal characteristics in terms of cell viability, magnetic properties, and induction heating capacity, which surpass those of the commercial magnetic fluid FluidMag-CT employed in hyperthermia treatment.


Subject(s)
Biocompatible Materials , Ferric Compounds , Magnetite Nanoparticles , Biocompatible Materials/chemistry , Silicon Dioxide/chemistry , Ferrosoferric Oxide , Heating , Ceramics/pharmacology , Ceramics/chemistry
4.
Int Endod J ; 57(6): 727-744, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38436622

ABSTRACT

AIMS: This study aimed to investigate the anti-inflammatory and odontoblastic effects of cerium-containing mesoporous bioactive glass nanoparticles (Ce-MBGNs) on dental pulp cells as novel pulp-capping agents. METHODOLOGY: Ce-MBGNs were synthesized using a post-impregnation strategy based on the antioxidant properties of Ce ions and proposed the first use of Ce-MBGNs for pulp-capping application. The biocompatibility of Ce-MBGNs was analysed using the CCK-8 assay and apoptosis detection. Additionally, the reactive oxygen species (ROS) scavenging ability of Ce-MBGNs was measured using the 2,7-Dichlorofuorescin Diacetate (DCFH-DA) probe. The anti-inflammatory effect of Ce-MBGNs on THP-1 cells was further investigated using flow cytometry and quantitative real-time polymerase chain reaction (RT-qPCR). Moreover, the effect of Ce-MBGNs on the odontoblastic differentiation of the dental pulp cells (DPCs) was assessed by combined scratch assays, RT-qPCR, western blotting, immunocytochemistry, Alizarin Red S staining and tissue-nonspecific alkaline phosphatase staining. Analytically, the secretions of tumour necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) were detected with enzyme-linked immunosorbent assay (ELISA). RESULTS: Ce-MBGNs were confirmed to effectively scavenge ROS in THP-1-derived macrophages and DPCs. Flow cytometry and RT-qPCR assays revealed that Ce-MBGNs significantly inhibited the M1 polarization of macrophages (Mφ). Furthermore, the protein levels of TNF-α and IL-1ß were downregulated in THP-1-derived macrophages after stimulation with Ce-MBGNs. With a step-forward virtue of promoting the odontoblastic differentiation of DPCs, we further confirmed that Ce-MBGNs could regulate the formation of a conductive immune microenvironment with respect to tissue repair in DPCs, which was mediated by macrophages. CONCLUSIONS: Ce-MBGNs protected cells from self-produced oxidative damage and exhibited excellent immunomodulatory and odontoblastic differentiation effects on DPCs. As a pulp-capping agent, this novel biomaterial can exert anti-inflammatory effects and promote restorative dentine regeneration in clinical treatment. We believe that this study will stimulate further correlative research on the development of advanced pulp-capping agents.


Subject(s)
Anti-Inflammatory Agents , Cerium , Dental Pulp , Nanoparticles , Dental Pulp/cytology , Dental Pulp/drug effects , Cerium/pharmacology , Humans , Anti-Inflammatory Agents/pharmacology , Reactive Oxygen Species/metabolism , Tumor Necrosis Factor-alpha/metabolism , Ceramics/pharmacology , Cell Differentiation/drug effects , Glass , Odontoblasts/drug effects , Regeneration/drug effects , THP-1 Cells , Pulp Capping and Pulpectomy Agents/pharmacology , Interleukin-1beta/metabolism , Apoptosis/drug effects , Porosity , Cells, Cultured
5.
J Biomed Mater Res A ; 112(7): 1124-1137, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38433700

ABSTRACT

This work presents the effect of the silicocarnotite (SC) and nagelschmidtite (Nagel) phases on in vitro osteogenesis. The known hydroxyapatite of biological origin (BHAp) was used as a standard of osteoconductive characteristics. The evaluation was carried out in conventional and osteogenic media for comparative purposes to assess the osteogenic ability of the bioceramics. First, the effect of the material on cell viability at 24 h, 7 and 14 days of incubation was evaluated. In addition, cell morphology and attachment on dense bioceramic surfaces were observed by fluorescence microscopy. Specifically, alkaline phosphatase (ALP) activity was evaluated as an osteogenic marker of the early stages of bone cell differentiation. Mineralized extracellular matrix was observed by calcium phosphate deposits and extracellular vesicle formation. Furthermore, cell phenotype determination was confirmed by scanning electron microscope. The results provided relevant information on the cell attachment, proliferation, and osteogenic differentiation processes after 7 and 14 days of incubation. Finally, it was demonstrated that SC and Nagel phases promote cell proliferation and differentiation, while the Nagel phase exhibited a superior osteoconductive behavior and could promote MC3T3-E1 cell differentiation to a higher extent than SC and BHAp, which was reflected in a higher number of deposits in a shorter period for both conventional and osteogenic media.


Subject(s)
Cell Differentiation , Ceramics , Durapatite , Osteoblasts , Osteogenesis , Silicates , Animals , Mice , Durapatite/chemistry , Durapatite/pharmacology , Ceramics/chemistry , Ceramics/pharmacology , Osteoblasts/cytology , Osteoblasts/metabolism , Osteoblasts/drug effects , Silicates/chemistry , Silicates/pharmacology , Cell Differentiation/drug effects , Osteogenesis/drug effects , Cell Proliferation/drug effects , Biocompatible Materials/chemistry , Alkaline Phosphatase/metabolism , Calcium Compounds/pharmacology , Calcium Compounds/chemistry , Cell Survival/drug effects , Cell Adhesion/drug effects , Extracellular Matrix/metabolism , 3T3 Cells , Cell Line
6.
Adv Healthc Mater ; 13(13): e2303217, 2024 May.
Article in English | MEDLINE | ID: mdl-38363057

ABSTRACT

Osteochondral defects are often accompanied by excessive reactive oxygen species (ROS) caused by osteoarthritis or acute surgical inflammation. An inflammatory environment containing excess ROS will not only hinder tissue regeneration but also impact the quality of newly formed tissues. Therefore, there is an urgent need to develop scaffolds with both ROS scavenging and osteochondral repair functions to promote and protect osteochondral tissue regeneration. In this work, by using 3D printing technology, a composite scaffold based on cobalt-incorporated chloroapatite (Co-ClAP) bioceramics, which possesses ROS-scavenging activity and can support cell proliferation, adhesion, and differentiation, is developed. Benefiting from the catalytic activity of Co-ClAP bioceramics, the composite scaffold can protect cells from oxidative damage under ROS-excessive conditions, support their directional differentiation, and simultaneously mediate an anti-inflammatory microenvironment. In addition, it is also confirmed by using rabbit osteochondral defect model that the Co-ClAP/poly(lactic-co-glycolic acid) scaffold can effectively promote the integrated regeneration of cartilage and subchondral bone, exhibiting an ideal repair effect in vivo. This study provides a promising strategy for the treatment of defects with excess ROS and inflammatory microenvironments.


Subject(s)
Bone Regeneration , Ceramics , Cobalt , Printing, Three-Dimensional , Tissue Scaffolds , Animals , Rabbits , Tissue Scaffolds/chemistry , Cobalt/chemistry , Ceramics/chemistry , Ceramics/pharmacology , Bone Regeneration/drug effects , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Reactive Oxygen Species/metabolism , Antioxidants/chemistry , Antioxidants/pharmacology , Tissue Engineering/methods , Cell Proliferation/drug effects , Apatites/chemistry , Cell Differentiation/drug effects , Chondrocytes/cytology , Chondrocytes/drug effects , Chondrocytes/metabolism
7.
J Biomed Mater Res B Appl Biomater ; 112(2): e35388, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38334714

ABSTRACT

The trace element strontium (Sr) enhances new bone formation. However, delivering Sr, like other materials, in a sustained manner from a ceramic bone graft substitute (BGS) is difficult. We developed a novel ceramic BGS, polyphosphate dicalcium phosphate dehydrate (P-DCPD), which delivers embedded drugs in a sustained pattern. This study assessed the in vitro and in vivo performance of Sr-doped P-DCPD. In vitro P-DCPD and 10%Sr-P-DCPD were nontoxic and eluents from 10%Sr-P-DCPD significantly enhanced osteoblastic MC3T3 cell differentiation. A sustained, zero-order Sr release was observed from 10%Sr-P-DCPD for up to 70 days. When using this BGS in a rat calvaria defect model, both P-DCPD and 10% Sr-P-DCPD were found to be biocompatible and biodegradable. Histologic data from decalcified and undecalcified tissue showed that 10%Sr-P-DCPD had more extensive new bone formation compared with P-DCPD 12-weeks after surgery and the 10%Sr-P-DCPD had more organized new bone and much less fibrous tissue at the defect margins. The new bone was formed on the surface of the degraded ceramic debris within the bone defect area. P-DCPD represented a promising drug-eluting BGS for repair of critical bone defects.


Subject(s)
Bone Substitutes , Calcium Phosphates , Phosphates , Polyphosphates , Rats , Animals , Polyphosphates/pharmacology , Bone Substitutes/pharmacology , Strontium/pharmacology , Ceramics/pharmacology , Skull
8.
Int Endod J ; 57(6): 682-699, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38403990

ABSTRACT

AIM: This study aimed to determine the effects of iRoot BP Plus on receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis in vitro and inflammation-mediated bone resorption in vivo and investigated the underlying molecular mechanisms. METHODOLOGY: CCK-8 was performed to test cell viability in RANKL-induced RAW 264.7 cells and BMDMs in response to iRoot BP Plus. The effect of iRoot BP Plus on osteoclastogenesis was determined using TRAP staining and phalloidin staining, respectively. Pit formation assay was conducted to measure osteoclast resorptive capacity. Western blot and qPCR were performed to examine osteoclast-related proteins and gene expression, respectively. Western blot was also used to investigate the signalling pathways involved. For in vivo experiments, an LPS-induced mouse calvarial bone resorption model was established to analyse the effect of iRoot BP Plus on bone resorption (n = 6 per group). At 7 days, mouse calvaria were collected and prepared for histological analysis. RESULTS: We identified that iRoot BP Plus extracts significantly attenuated RANKL-induced osteoclastogenesis, reduced sealing zone formation, restrained osteolytic capacity and decreased osteoclast-specific gene expression (p < .01). Mechanistically, iRoot BP Plus extracts reduced TRAF6 via proteasomal degradation, then suppressed the phosphorylation of mitogen-activated protein kinases (MAPKs), blocked the nuclear translocation of c-Fos and diminished nuclear factor-κB (NF-κB) p65 and NFATc1 accumulation. Consistent with the in vitro results, iRoot BP Plus extracts attenuated osteoclast activity thus protecting against inflammatory bone resorption in vivo (p < .05), which was accompanied by a suppression of TRAF6, c-Fos, NFATc1 and cathepsin K expression. CONCLUSION: These findings provide valuable insights into the signalling mechanisms underlying nanoparticulate bioceramic putty-mediated bone homeostasis.


Subject(s)
Bone Resorption , Osteoclasts , Osteogenesis , RANK Ligand , Signal Transduction , TNF Receptor-Associated Factor 6 , Animals , Mice , TNF Receptor-Associated Factor 6/metabolism , Signal Transduction/drug effects , Bone Resorption/metabolism , RAW 264.7 Cells , Osteogenesis/drug effects , Osteoclasts/drug effects , RANK Ligand/metabolism , Nanoparticles , Ceramics/pharmacology , Inflammation/metabolism , Cell Survival/drug effects
9.
Adv Healthc Mater ; 13(13): e2303182, 2024 May.
Article in English | MEDLINE | ID: mdl-38298104

ABSTRACT

Infective bone defect is increasingly threatening human health. How to achieve the optimal antibacterial activity and regenerative repair of infective bone defect simultaneously is a huge challenge in clinic. Herein, this work reports a rational integration of Mn single-atom nanozyme into the 3D-printed bioceramic scaffolds (Mn/HSAE@BCP scaffolds). The integrated Mn/HSAE@BCP scaffolds can catalyze the conversion of H2O2 to produce hydroxyl radical (•OH) and superoxide anion (O2 •-) through cascade reaction. Besides, the prominent thermal conversion efficiency of Mn/HSAE@BCP scaffolds can be utilized for sonodynamic therapy (SDT). The synergetic strategy of chemodynamic therapy (CDT)/SDT enables the sufficient generation of reactive oxygen species (ROS) to kill Staphylococcus aureus (S. aureus) or Escherichia coli (E. coli). Furthermore, the enhanced antibacterial efficacy of Mn/HSAE@BCP scaffolds is beneficial to upregulate the expression of osteogenesis-related markers (such as collagen 1(COL1), Runt-related transcription factor 2 (Runx2), osteocalcin (OCN), and osteoprotegerin (OPG)) in vitro and further promote bone regeneration in vivo. The results demonstrate the good potential of Mn/HSAE@BCP scaffolds for the enhanced antibacterial activity and bone regeneration, which provide an effective method for the treatment of clinical infective bone defect.


Subject(s)
Anti-Bacterial Agents , Bone Regeneration , Ceramics , Escherichia coli , Manganese , Printing, Three-Dimensional , Staphylococcus aureus , Tissue Scaffolds , Bone Regeneration/drug effects , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Tissue Scaffolds/chemistry , Staphylococcus aureus/drug effects , Ceramics/chemistry , Ceramics/pharmacology , Animals , Escherichia coli/drug effects , Manganese/chemistry , Osteogenesis/drug effects , Humans
10.
Biomaterials ; 304: 122406, 2024 01.
Article in English | MEDLINE | ID: mdl-38096618

ABSTRACT

Calcium phosphate ceramics-based biomaterials were reported to have good biocompatibility and osteoinductivity and have been widely applied for bone defect repair and regeneration. However, the mechanism of their osteoinductivity is still unclear. In our study, we established an ectopic bone formation in vivo model and an in vitro macrophage cell co-culture system with calcium phosphate ceramics to investigate the effect of biphasic calcium phosphate on osteogenesis via regulating macrophage M1/M2 polarization. Our micro-CT data suggested that biphasic calcium phosphate had significant osteoinductivity, and the fluorescence co-localization detection found increased F4/80+/integrin αvß3+ macrophages surrounding the biphasic calcium phosphate scaffolds. Besides, our study also revealed that biphasic calcium phosphate promoted M2 polarization of macrophages via upregulating integrin αvß3 expression compared to tricalcium phosphate, and the increased M2 macrophages could subsequently augment the osteogenic differentiation of MSCs in a TGFß mediated manner. In conclusion, we demonstrated that macrophages subjected to biphasic calcium phosphate could polarize toward M2 phenotype via triggering integrin αvß3 and secrete TGFß to increase the osteogenesis of MSCs, which subsequently enhances bone regeneration.


Subject(s)
Mesenchymal Stem Cells , Osteogenesis , Integrin alphaVbeta3/metabolism , Calcium Phosphates/pharmacology , Macrophages/metabolism , Transforming Growth Factor beta/metabolism , Ceramics/pharmacology
11.
J Biomed Mater Res B Appl Biomater ; 112(1): e35340, 2024 01.
Article in English | MEDLINE | ID: mdl-37929804

ABSTRACT

Effective bone substitute biomaterials remain an important challenge in patients with large bone defects. Glass ceramics produced by different synthesis routes may result in changes in the material physicochemical properties and consequently affect the success or failure of the bone healing response. To investigate the differences in the orchestration of the inflammatory and healing process in bone grafting and repair using different glass-ceramic routes production. Thirty male Wistar rats underwent surgical unilateral parietal defects filled with silicate glass-ceramic produced by distinct routes: BS - particulate glass-ceramic produced via the fusion/solidification route, and BG - particulate glass-ceramic produced via the sol-gel route. After 7, 14, and 21 days from biomaterial grafting, parietal bones were removed to be analyzed under H&E and Massons' Trichome staining, and immunohistochemistry for CD206, iNOS, and TGF-ß. Our findings demonstrated that the density of lymphocytes and plasma cells was significantly higher in the BS group at 45, and 7 days compared to the BG group, respectively. Furthermore, a significant increase of foreign body giant cells (FBGCs) in the BG group at day 7, compared to BS was found, demonstrating early efficient recruitment of FBGCs against sol-gel-derived glass-ceramic particulate (BS group). According to macrophage profiles, CD206+ macrophages enhanced at the final periods of both groups, being significantly higher at 45 days of BS compared to the BG group. On the other hand, the density of transformation growth factor beta (TGF-ß) positive cells on 21 days were the highest in BG, and the lowest in the BS group, demonstrating a differential synergy among groups. Noteworthy, TGF-ß+ cells were significantly higher at 21 days of BG compared to the BS group. Glass-ceramic biomaterials can act differently in the biological process of bone remodeling due to their route production, being the sol-gel route more efficient to activate M2 macrophages and specific FBGCs compared to the traditional route. Altogether, these features lead to a better understanding of the effectiveness of inflammatory response for biomaterial degradation and provide new insights for further preclinical and clinical studies involved in bone healing.


Subject(s)
Biocompatible Materials , Bone Substitutes , Humans , Rats , Animals , Male , Materials Testing , Rats, Wistar , Biocompatible Materials/chemistry , Bone Regeneration , Bone Substitutes/chemistry , Ceramics/pharmacology , Ceramics/chemistry , Macrophages , Transforming Growth Factor beta , Glass/chemistry
12.
ACS Appl Mater Interfaces ; 16(1): 376-388, 2024 Jan 10.
Article in English | MEDLINE | ID: mdl-38131318

ABSTRACT

The aim of the experiment was to evaluate the biocompatibility of four 3D-printed biomaterials planned for use in the surgical treatment of finger amputees: Ti-6Al-4 V (Ti64), ZrO2-Al2O3 ceramic material (ATZ20), and osteoconductive (anodized Ti64) and antibacterial (Hydroxyapatite, HAp) coatings that adhere well to materials dedicated to finger bone implants. The work concerns the correlation of mechanical, microstructural, and biological properties of dedicated materials. Biological tests consisted of determining the overall cytotoxicity of the organism on the basis of in vivo tests carried out in accordance with the ISO 10993-6 and ISO 10993-11 standards. Clinical observations followed by diagnostic examinations, histopathological evaluation, and biochemical characterization showed no significant differences between control and tested groups of animals. The wound healed without complication, and no pathological effects were found. The wear test showed the fragility of the hydroxyapatite thin layer and the mechanical stability of the zirconia-based ceramic substrate. Electron microscopy observations revealed the layered structure of tested substrates and coatings.


Subject(s)
Biocompatible Materials , Prostheses and Implants , Animals , Biocompatible Materials/pharmacology , Biocompatible Materials/chemistry , Durapatite/pharmacology , Ceramics/pharmacology , Titanium/pharmacology , Titanium/chemistry , Alloys/pharmacology , Alloys/chemistry , Surface Properties , Materials Testing
13.
Macromol Biosci ; 24(4): e2300295, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38102878

ABSTRACT

Decellularized extracellular matrix is often used to create an in vivo-like environment that supports cell growth and proliferation, as it reflects the micro/macrostructure and molecular composition of tissues. On the other hand, bioactive glasses (BG) are surface-reactive glass-ceramics that can convert to hydroxyapatite in vivo and promote new bone formation. This study is designed to evaluate the key properties of a novel angiogenic and osteogenic biocomposite graft made of bovine decellularized bone matrix (DBM) hydrogel and 45S5 BG microparticles (10 and 20 wt%) to combine the existing superior properties of both biomaterial classes. Morphological, physicochemical, mechanical, and thermal characterizations of DBM and DBM/BG composite hydrogels are performed. Their in vitro biocompatibility is confirmed by cytotoxicity and hemocompatibility analyses. Ex vivo chick embryo aortic arch and ex ovo chick chorioallantoic membrane (CAM) assays reveal that the present pro-angiogenic property of DBM hydrogels is enhanced by the incorporation of BG. Histochemical stainings (Alcian blue and Alizarin red) and digital image analysis of ossification on hind limbs of embryos used in the CAM model reveal the osteogenic potential of biomaterials. The findings support the notion that the developed DBM/BG composite hydrogel constructs have the potential to be a suitable graft for bone repair.


Subject(s)
Hydrogels , Osteogenesis , Chick Embryo , Animals , Cattle , Hydrogels/pharmacology , Bone Matrix , Biocompatible Materials/pharmacology , Biocompatible Materials/chemistry , Glass/chemistry , Chickens , Ceramics/pharmacology , Ceramics/chemistry
14.
J Biomed Mater Res A ; 112(2): 193-209, 2024 02.
Article in English | MEDLINE | ID: mdl-37680167

ABSTRACT

Hydroxyapatite (HA) bioceramic is a promising substitute for bone defects, and the surface properties are major factors that influence bioactivity and osteoinductivity. In this study, two kinds of HA bioceramics with nanoscale (n-HA) and microscale (m-HA) surface topography were designed to mimic the natural bone, thus enhancing the stimulation of osteogenic differentiation and revealing the potential mechanism. Compared to m-HA, n-HA owned a larger surface roughness, a stronger wettability, and reduced hardness and indentation modulus. Based on these properties, n-HA could maintain the conformation of vitronectin better than m-HA, which may contribute to higher cellular activities and a stronger promotion of osteogenic differentiation of mesenchymal stem cells (MSCs). Further RNA sequencing analysis compared the molecular expression between n-HA and m-HA. Six hundred twenty-seven differentially expressed genes were identified in MSCs, and 17 upregulated genes and 610 downregulated genes were included when n-HA compared to m-HA. The GO cluster analysis and enriched Kyoto encyclopedia of genes and genome signaling pathways revealed a close correlation with the immune process in both upregulated (chemokine signaling pathway and cytokine-cytokine receptor interaction) and downregulated pathways (osteoclasts differentiation). It suggested that the nanoscale surface topography of HA enhanced the osteoinductivity of MSCs and could not be separated from its regulation of immune function and the retention of adsorbed protein conformation.


Subject(s)
Durapatite , Mesenchymal Stem Cells , Durapatite/pharmacology , Durapatite/metabolism , Osteogenesis/genetics , Cell Differentiation , Ceramics/pharmacology
15.
Sci Rep ; 13(1): 22079, 2023 12 12.
Article in English | MEDLINE | ID: mdl-38086987

ABSTRACT

Posterolateral spinal fusion (PLF) is a procedure used for the treatment of degenerative spine disease. In this study we evaluated Osteogrow-C, a novel osteoinductive device comprised of recombinant human Bone morphogenetic protein 6 (rhBMP6) dispersed in autologous blood coagulum with synthetic ceramic particles, in the sheep PLF model. Osteogrow-C implants containing 74-420 or 1000-1700 µm ceramic particles (TCP/HA 80/20) were implanted between L4-L5 transverse processes in sheep (Ovis Aries, Merinolaandschaf breed). In the first experiment (n = 9 sheep; rhBMP6 dose 800 µg) the follow-up period was 27 weeks while in the second experiment (n = 12 sheep; rhBMP6 dose 500 µg) spinal fusion was assessed by in vivo CT after 9 weeks and at the end of the experiment after 14 (n = 6 sheep) and 40 (n = 6 sheep) weeks. Methods of evaluation included microCT, histological analyses and biomechanical testing. Osteogrow-C implants containing both 74-420 and 1000-1700 µm ceramic particles induced radiographic solid fusion 9 weeks following implantation. Ex-vivo microCT and histological analyses revealed complete osseointegration of newly formed bone with adjacent transverse processes. Biomechanical testing confirmed that fusion between transverse processes was complete and successful. Osteogrow-C implants induced spinal fusion in sheep PLF model and therefore represent a novel therapeutic solution for patients with degenerative disc disease.


Subject(s)
Bone Morphogenetic Proteins , Spinal Fusion , Humans , Animals , Sheep , Bone Morphogenetic Proteins/pharmacology , Transforming Growth Factor beta , Lumbar Vertebrae/pathology , Bone Morphogenetic Protein 2 , Bone Morphogenetic Protein 6 , Spinal Fusion/methods , Ceramics/pharmacology , Calcium Phosphates/pharmacology , Bone Transplantation/methods
16.
Biomater Adv ; 154: 213644, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37778294

ABSTRACT

Recent advancements in medical technology and increased interdisciplinary research have facilitated the development of the field of medical engineering. Specifically, in bone repair, researchers and potential users have placed greater demands on orthopedic implants regarding their biocompatibility, degradation rates, antibacterial properties, and other aspects. In response, our team developed composite ceramic samples using degradable materials calcium phosphate and magnesium oxide through the vat photopolymerization (VP) technique. The calcium phosphate content in each sample was, respectively, 80 %, 60 %, 40 %, and 20 %. To explore the relationship between the biocompatibility, antibacterial activity, and MgO content of the samples, we cultured them with osteoblasts (MC3T3-E1), Escherichia coli (a gram-negative bacterium), and Staphylococcus aureus (a gram-positive bacterium). Our results demonstrate that as the MgO content of the sample increases, its biocompatibility improves but its antibacterial activity decreases. Regarding the composite material samples, the 20 % calcium phosphate content group exhibited the best biocompatibility. However, after 0.5 h of co-cultivation, the antibacterial rates of all groups except the 20 % calcium phosphate content group co-cultured with S. aureus exceed 80 %. Furthermore, after 3 h, the antibacterial rates against E. coli exceed 95 % in all groups. This is because higher levels of MgO correspond to lower pH values and Mg2+ concentrations in the cell and bacterial culture solutions, which ultimately promote cell and bacterial proliferation. This elevates the biocompatibility of the samples, albeit at the expense of their antimicrobial efficacy. Thus, modulating the MgO content in the composite ceramic samples provides a strategy to develop gradient composite scaffolds for better control of their biocompatibility and antibacterial performance during different stages of bone regeneration.


Subject(s)
Magnesium Oxide , Staphylococcus aureus , Magnesium Oxide/pharmacology , Magnesium Oxide/chemistry , Escherichia coli , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Calcium Phosphates/pharmacology , Calcium Phosphates/chemistry , Ceramics/pharmacology , Technology
17.
Int J Mol Sci ; 24(13)2023 Jun 24.
Article in English | MEDLINE | ID: mdl-37445749

ABSTRACT

Implantology is crucial for restoring aesthetics and masticatory function in oral rehabilitation. Despite its advantages, certain issues, such as bacterial infection, may still arise that hinder osseointegration and result in implant rejection. This work aims to address these challenges by developing a biomaterial for dental implant coating based on 45S5 Bioglass® modified by zirconium insertion. The structural characterization of the glasses, by XRD, showed that the introduction of zirconium in the Bioglass network at a concentration higher than 2 mol% promotes phase separation, with crystal phase formation. Impedance spectroscopy was used, in the frequency range of 102-106 Hz and the temperature range of 200-400 K, to investigate the electrical properties of these Bioglasses, due to their ability to store electrical charges and therefore enhance the osseointegration capacity. The electrical study showed that the presence of crystal phases, in the glass ceramic with 8 mol% of zirconium, led to a significant increase in conductivity. In terms of biological properties, the Bioglasses exhibited an antibacterial effect against Gram-positive and Gram-negative bacteria and did not show cytotoxicity for the Saos-2 cell line at extract concentrations up to 25 mg/mL. Furthermore, the results of the bioactivity test revealed that within 24 h, a CaP-rich layer began to form on the surface of all the samples. According to our results, the incorporation of 2 mol% of ZrO2 into the Bioglass significantly improves its potential as a coating material for dental implants, enhancing both its antibacterial and osteointegration properties.


Subject(s)
Dental Implants , Zirconium/pharmacology , Zirconium/chemistry , Anti-Bacterial Agents , Gram-Negative Bacteria , Gram-Positive Bacteria , Ceramics/pharmacology , Ceramics/chemistry , Glass/chemistry , Surface Properties
18.
Molecules ; 28(13)2023 Jul 06.
Article in English | MEDLINE | ID: mdl-37446899

ABSTRACT

Difficult-to-treat bone damage resulting from metabolic bone diseases, mechanical injuries, or tumor resection requires support in the form of biomaterials. The aim of this research was to optimize the concentration of individual components of polymer-ceramic nanocomposite granules (nanofilled polymer composites) for application in orthopedics and maxillofacial surgery to fill small bone defects and stimulate the regeneration process. Two types of granules were made using nanohydroxyapatite (nanoHA) and chitosan-based matrix (agarose/chitosan or curdlan/chitosan), which served as binder for ceramic nanopowder. Different concentrations of the components (nanoHA and curdlan), foaming agent (sodium bicarbonate-NaHCO3), and chitosan solvent (acetic acid-CH3COOH) were tested during the production process. Agarose and chitosan concentrations were fixed to be 5% w/v and 2% w/v, respectively, based on our previous research. Subsequently, the produced granules were subjected to cytotoxicity testing (indirect and direct contact methods), microhardness testing (Young's modulus evaluation), and microstructure analysis (porosity, specific surface area, and surface roughness) in order to identify the biomaterial with the most favorable properties. The results demonstrated only slight differences among the resultant granules with respect to their microstructural, mechanical, and biological properties. All variants of the biomaterials were non-toxic to a mouse preosteoblast cell line (MC3T3-E1), supported cell growth on their surface, had high porosity (46-51%), and showed relatively high specific surface area (25-33 m2/g) and Young's modulus values (2-10 GPa). Apart from biomaterials containing 8% w/v curdlan, all samples were predominantly characterized by mesoporosity. Nevertheless, materials with the greatest biomedical potential were obtained using 5% w/v agarose, 2% w/v chitosan, and 50% or 70% w/v nanoHA when the chitosan solvent/foaming agent ratio was equal to 2:2. In the case of the granules containing curdlan/chitosan matrix, the most optimal composition was as follows: 2% w/v chitosan, 4% w/v curdlan, and 30% w/v nanoHA. The obtained test results indicate that both manufactured types of granules are promising implantable biomaterials for filling small bone defects that can be used in maxillofacial surgery.


Subject(s)
Chitosan , Nanocomposites , Animals , Mice , Chitosan/pharmacology , Chitosan/chemistry , Tissue Scaffolds/chemistry , Polymers , Sepharose/chemistry , Biocompatible Materials/pharmacology , Biocompatible Materials/chemistry , Bone Regeneration , Nanocomposites/chemistry , Ceramics/pharmacology , Solvents , Durapatite/chemistry
19.
Dent Mater J ; 42(4): 559-567, 2023 Aug 02.
Article in English | MEDLINE | ID: mdl-37302824

ABSTRACT

This study aimed to investigate the effects of two antioxidants and their application time on the fracture strength of computer-aided design and computer-aided manufacturing (CAD/CAM)-fabricated ceramic laminate veneers to bleached enamel, as well as their effects on the bonding interface micromorphology. Eight groups were set: Group NC (without bleaching and antioxidant treatment); Group NA (bleaching without antioxidant treatment); Group SA30, SA60, SA120 and Group PAC30, PAC60, PAC120 (bleaching and treating with sodium ascorbate or proanthocyanidins for 30, 60, and 120 min, respectively). After cementation of veneers, fracture strength values and failure modes were analyzed. The bonding interface morphology was observed by confocal laser scanning microscopy. The fracture strength was impaired when cementation procedure was performed immediately after bleaching. This reduction in fracture strength was reestablished with antioxidant treatment, and an extended treatment time contributed to better improvement. The resin tags at the bonding interfaces of the bleached enamel were impaired. Antioxidant treatments were able to reverse this unfavorable trend.


Subject(s)
Antioxidants , Dental Bonding , Antioxidants/pharmacology , Flexural Strength , Ceramics/pharmacology , Dental Enamel , Computer-Aided Design , Dental Bonding/methods , Dental Veneers , Materials Testing , Resin Cements/pharmacology
20.
J Biomed Mater Res B Appl Biomater ; 111(10): 1824-1839, 2023 10.
Article in English | MEDLINE | ID: mdl-37255008

ABSTRACT

Although yttria-stabilized tetragonal zirconia polycrystals (Y-TZP) ceramics have been widely used as restorative materials due to their high mechanical strength, unique esthetic effect, and good biocompatibility, their general application to implant materials is still limited by their biological inertness and hydrothermal aging phenomenon. Existing studies have attempted to investigate how to enhance the bioactivity or hydrothermal aging resistance of Y-TZP. Still, more studies need to be done on the modification that combines these two aspects. In this study, Y-TZP was prepared by 77S bioactive glass (BG) sol and akermanite (AKT) sol infiltration and microwave sintering, which provided Y-TZP with high bioactivity while maintaining resistance to hydrothermal aging. Results of phase composition evaluation, microstructural characteristics, and mechanical property tests showed that modified Y-TZP specimens exhibited little or no tetragonal-to-monoclinic (t → m) transformation and maintained relatively high mechanical properties after accelerated hydrothermal aging treatment. The in vitro biological behaviors showed that the introduction of 77S BG and AKT significantly promoted cell adhesion, spreading, viability, and proliferation on the surface of modified Y-TZP ceramics. Therefore, this modification could effectively enhance the bioactivity and hydrothermal aging resistance of Y-TZP ceramics for its application in dental implant materials.


Subject(s)
Dental Implants , Proto-Oncogene Proteins c-akt , Materials Testing , Surface Properties , Zirconium/pharmacology , Zirconium/chemistry , Yttrium/chemistry , Ceramics/pharmacology , Ceramics/chemistry , Dental Materials
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