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Search Results (2,231)

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Keywords = bone defect

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16 pages, 692 KiB  
Systematic Review
Post-Traumatic Segmental Tibial Defects Management: A Systematic Review of the Literature
by Giovanni Marrara, Biagio Zampogna, Viktor Dietrich Schick, Leone Larizza, Paolo Rizzo, Ilaria Sanzarello, Matteo Nanni and Danilo Leonetti
Appl. Sci. 2025, 15(1), 64; https://doi.org/10.3390/app15010064 (registering DOI) - 25 Dec 2024
Abstract
Introduction: Segmental tibial defects pose significant challenges in orthopedic surgery due to their complexity and high complication rates. This systematic review aimed to evaluate both the effectiveness and outcomes of distraction osteogenesis (D.O.) and the Masquelet technique in treating post-traumatic segmental tibial defects. [...] Read more.
Introduction: Segmental tibial defects pose significant challenges in orthopedic surgery due to their complexity and high complication rates. This systematic review aimed to evaluate both the effectiveness and outcomes of distraction osteogenesis (D.O.) and the Masquelet technique in treating post-traumatic segmental tibial defects. Materials and Methods: A literature search was performed on PubMed, Scopus, and Cochrane. Relevant retrospective and prospective observational studies with a minimum of 12 months follow-up were included. The primary outcome was bone union rate; the secondary outcomes were the type and rate of complications and the clinical and radiological outcomes. Results: Twenty-seven studies met the inclusion criteria, 18 studies reported data on D.O. and 9 on the Masquelet technique. D.O. demonstrated an overall union rate of 79.4% across 422 patients, and the Masquelet technique demonstrated an overall bone union rate of 85% across 113 patients. For D.O., on average, there was one complication per patient, and with the Masquelet technique, there were 0.5 complications per patient. Conclusions: D.O. and the Masquelet technique are the main treatment options for post-traumatic segmental tibial defects. Although union rates are similar, the Masquelet technique showed fewer complications. Treatment choice should consider patient-specific factors and more comparative studies are needed. Full article
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<p>PRISMA flow chart of the literature search.</p>
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25 pages, 5065 KiB  
Article
Comparison between Nano-Hydroxyapatite/Beta-Tricalcium Phosphate Composite and Autogenous Bone Graft in Bone Regeneration Applications: Biochemical Mechanisms and Morphological Analysis
by Igor da Silva Brum, Lucio Frigo, Jemima Fuentes Ribeiro da Silva, Bianca Torres Ciambarella, Ana Lucia Rosa Nascimento, Mario José dos Santos Pereira, Carlos Nelson Elias and Jorge José de Carvalho
Int. J. Mol. Sci. 2025, 26(1), 52; https://doi.org/10.3390/ijms26010052 - 24 Dec 2024
Abstract
It was assumed that only autogenous bone had appropriate osteoconductive and osteoindutive properties for bone regeneration, but this assumption has been challenged. Many studies have shown that synthetic biomaterials must be considered as the best choice for guided bone regeneration. The objective of [...] Read more.
It was assumed that only autogenous bone had appropriate osteoconductive and osteoindutive properties for bone regeneration, but this assumption has been challenged. Many studies have shown that synthetic biomaterials must be considered as the best choice for guided bone regeneration. The objective of this work is to compare the performances of nanohydroxyapatite/β-tricalcium phosphate (n-HA/β-TCP) composite and autogenous bone grafting in bone regeneration applications. The composite was characterized by scanning electron microscopy (SEM) and used as an allograft in bone defects formed in adult Wistar rats. The bone defects in the dorsal cranium were grafted with autogenous bone on one side and the n-HA/β-TCP composite on the other. Histomorphometry evaluation via different staining methods (Goldner trichrome, PAS, and Sirius red) and TRAP histochemistry were performed. Immunohistomorphometries of OPN, Cathepsin K, TRAP, acid phosphatase, VEGF, NFκ-β, MMP-2, MMP-9, and TGF-β were carried out. The RT-PCR method was also applied to to RANK-L, Osteocalcine, Alcaline Phosphatase, Osterix, and Runx2. The results showed that for all morphometric evaluations with the different staining methods, histochemistry, and immunohistochemistry, VEGF and NFκ-β were higher in the n-HA/β-TCP composite group than in the autogenous bone graft group. The RT-PCR markers were higher in the autogenous bone group than in the n-HA/β-TCP composite group. The n-HA/β-TCP composite exhibited enhanced cell–matrix interactions in bone remodeling, higher adhesion, proliferation, and differentiation, and increased vascularization. These results suggest that the n-HA/β-TCP composite induces faster bone formation than autogenous bone grafting. Full article
(This article belongs to the Special Issue Nano & Micro Materials in Healthcare 3.0)
16 pages, 47556 KiB  
Article
Customized 3D Allogenic Bone Blocks for Mandibular Buccal-Bone Reconstruction Increase Resistance to Tongue-Protrusion Forces: A Finite Element Analysis
by Sebastian Dominiak, Jennifer Majer, Christoph Bourauel, Ludger Keilig and Tomasz Gedrange
J. Funct. Biomater. 2025, 16(1), 1; https://doi.org/10.3390/jfb16010001 - 24 Dec 2024
Abstract
Background. The impact of tongue protrusion forces on the formation of malocclusions is well documented in academic literature. In the case of bone dehiscence of the buccal wall in front of the lower frontal teeth, this process may be even more pronounced. Augmentation [...] Read more.
Background. The impact of tongue protrusion forces on the formation of malocclusions is well documented in academic literature. In the case of bone dehiscence of the buccal wall in front of the lower frontal teeth, this process may be even more pronounced. Augmentation with 3D customized allogenic bone blocks (CABB) has been proposed as a potential solution for treating such defects. The objective was to assess the impact of bone block adjustment accuracy on the resistance of teeth to protrusion forces at various stages of alveolar bone loss. Methods: A finite element analysis (FEM) was conducted to ascertain whether augmentation with a CABB will result in increased resilience to tongue protrusion forces. Three-dimensional models of the mandible with dehiscenses were created, based on the dehiscences classification and modification proposed in the journal by the authors of regenerative method. The models feature a CABB positioned at three different distances: 0.1 mm, 0.4 mm, and 1.0 mm. The material parameters were as follows: bone (homogenous, isotropic, E = 2 GPa), teeth (E = 20 GPa), periodontal ligament (E = 0.44 MPa), and membrane between bones (E = 3.4 MPa). A tongue protrusion force within the range of 0–5 N was applied to each individual frontal tooth. Results: The use of an CABB has been shown to positively impact the stability of the teeth. The closer the bone block was placed to the alveolar bone, the more stable was the result. The best results were obtained with a ¼ dehiscence and 0.1 mm distance. Conclusions: The protrusive forces produced by the tongue might not be the biggest one, but in a presence of the bone loss they might have serious results. Even shortly after the surgery, CABB has a positive impact on the incisor resilience. Full article
(This article belongs to the Special Issue Advances in Biomaterials for Reconstructive Dentistry)
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<p>Initial models with dehiscence. (<b>A</b>) Model with visible PDL and invisible bone at ¼ dehiscence level; (<b>B</b>) initial model at ¼ dehiscence level; (<b>C</b>) initial model at 1/2 dehiscence level; (<b>D</b>) initial model at 3/4 dehiscence level.</p>
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<p>Finished model with stage 1 dehiscence and bone block placed 0.1 mm from the native bone.</p>
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<p>Tooth 31 displacement with the presence of ¼, ½ and ¾ root exposure at 0.1–1 mm spacing.</p>
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<p>The bar graphs illustrate the maximum displacement in relation to the level of dehiscence and the distance to the bone block on each tooth. The blue, orange, and gray bars represent the maximum displacement for different stages of bone dehiscence alone. Yellow, light blue and green are representing maximum displacement for different distances between the maternal bone and the bone block.</p>
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<p>Strains in PDL 31 with the presence of ¼, ½ and ¾ root exposure at the distances of 0.1–1 mm.</p>
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<p>The bar graphs illustrate the maximum strains in the PDL for all models and all force applications. The blue, orange, and gray bars represent the maximum strains for different stages of bone dehiscence. The yellow, light blue, and green bars represent the maximum strains for different distances between the maternal bone and the bone block.</p>
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<p>The location of the center of rotation on various teeth with different degrees of dehiscence and different membrane widths.</p>
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<p>Strain distribution in the presence of ¼, ½ and ¾ root exposure at the 0.1–1 mm distance.</p>
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<p>The pattern of stress accumulation around the screws that is reduced, regardless of the dehiscence stage or membrane width.</p>
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14 pages, 1148 KiB  
Article
RNA Sequencing Revealed a Weak Response of Gingival Fibroblasts Exposed to Hyaluronic Acid
by Layla Panahipour, Atefe Imani, Natália dos Santos Sanches, Hannes Kühtreiber, Michael Mildner and Reinhard Gruber
Bioengineering 2024, 11(12), 1307; https://doi.org/10.3390/bioengineering11121307 - 23 Dec 2024
Abstract
Hyaluronic acid was proposed to support soft tissue recession surgery and guided tissue regeneration. The molecular mechanisms through which hyaluronic acid modulates the response of connective tissue cells remain elusive. To elucidate the impact of hyaluronic acid on the connective tissue cells, we [...] Read more.
Hyaluronic acid was proposed to support soft tissue recession surgery and guided tissue regeneration. The molecular mechanisms through which hyaluronic acid modulates the response of connective tissue cells remain elusive. To elucidate the impact of hyaluronic acid on the connective tissue cells, we used bulk RNA sequencing to determine the changes in the genetic signature of gingival fibroblasts exposed to 1.6% cross-linked hyaluronic acid and 0.2% natural hyaluronic acid. Transcriptome-wide changes were modest. Even when implementing a minimum of 1.5 log2 fold-change and a significance threshold of 1.0 −log10, only a dozenth of genes were differentially expressed. Upregulated genes were PLK3, SLC16A6, IL6, HBEGF, DGKE, DUSP4, PTGS2, FOXC2, ATAD2B, NFATC2, and downregulated genes were MMP24 and PLXNA2. RT-PCR analysis supported the impact of hyaluronic acid on increasing the expression of a selected gene panel. The findings from bulk RNA sequencing suggest that gingival fibroblasts experience weak changes in their transcriptome when exposed to hyaluronic acid. Full article
(This article belongs to the Section Regenerative Engineering)
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<p>Principal component analysis for differentially expressed genes in gingival fibroblasts treated with HAc. The plot shows the projection of the top 500 genes onto the two-dimensional space spanned by the first and second principal components (PC1, PC2). The expression levels used as input are raw gene counts. Red is control, blue is HAc.</p>
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<p>Volcano plot analysis of differentially expressed genes in gingival fibroblasts treated with HAc. Volcano plot analysis identified upregulated (red) and downregulated (blue) genes in gingival fibroblasts treated with HAc. The annotated dots are data points with the largest (Manhattan) distance from the origin and are above the thresholds indicated by the dashed line. (<b>A</b>) The threshold was set to at least a 4.0-fold change and a significance level of <span class="html-italic">p</span> = 0.1. (<b>B</b>) Volcano plot of the top 50 genes with no statistical threshold.</p>
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<p>RT-PCR analysis of differentially expressed genes in gingival fibroblasts treated with HAc. Gingival fibroblasts were seeded onto a tissue culture-treated surface and, the following day, exposed to 3.6 mg/mL of HAc cross-linked and 0.4 mg/mL of HAc with sodium chloride for 6 h in serum-free DMEM followed by RT-PCR analysis. Gene expression changes were calculated by the ΔΔCT method, and findings are expressed as the x-fold increase compared to unstimulated cells, which have an expression level of 1. Statistics are based on a ratio-paired <span class="html-italic">t</span>-test, and data points represent independent experiments.</p>
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<p>RT-PCR and ELISA analysis of inflammatory genes in gingival fibroblasts treated with HAc. Gingival fibroblasts were seeded onto a tissue culture-treated surface and, the following day, exposed to 3.6 mg/mL of HAc cross-linked and 0.4 mg/mL of HAc or IL1β and TNFα at 10 ng/mL for 6 h in serum-free DMEM followed by RT-PCR analysis. Gene expression changes were calculated by the ΔΔCT method, and findings are expressed as an x-fold increase compared to unstimulated cells, which have an expression level of 1. Statistics are based on a ratio-paired <span class="html-italic">t</span>-test. Data points represent independent experiments.</p>
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<p>RT-PCR and ELISA analysis of inflammatory genes in primary murine macrophages treated with HAc. Murine bone marrow-derived macrophages were exposed to 3.6 mg/mL of cross-linked HAc and 0.4 mg/mL of HAc or LPS from <span class="html-italic">E. coli</span> at 100 ng/mL for 6 h in serum-free DMEM followed by RT-PCR analysis. Gene expression changes were calculated by the ΔΔCT method, and findings are expressed as an x-fold increase compared to unstimulated cells, which have an expression level of 1. Statistics is based on a ratio-paired <span class="html-italic">t</span>-test. Data points represent four independent experiments.</p>
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<p>Heat map of differentially expressed genes in gingival fibroblasts treated with HAc. The heat map is used to visualize the differentially expressed genes in untreated fibroblasts versus the fibroblasts exposed to HAc. The data set used was the differentially expressed genes with an adjusted <span class="html-italic">p</span>-value of <span class="html-italic">p</span> &lt; 0.05. This heatmap integrates the data from the three different fibroblast preparations. Turning from red to blue represents downregulated genes, and from blue to red represents upregulated genes. The color intensity reflects the expression levels of the raw data.</p>
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<p>STRING analysis of expression changes by HAc. Protein–protein association network and functional enrichment analyses of the 24 genes with a differential expression in gingival fibroblasts exposed to HAc. We identified three clusters of genes.</p>
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<p>g:Profiler analysis of differentially expressed genes in gingival fibroblasts treated with HAc. Enrichment analysis was performed using the g:Profiler online tool based on the selected 24 genes. Selected top significant pathways were highlighted and labeled numerically. Using the Benjamini–Hochberg method, the <span class="html-italic">p</span>-value was adjusted (Padj) for multiple tests.</p>
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11 pages, 4951 KiB  
Article
Stem Cells Within Three-Dimensional-Printed Scaffolds Facilitate Airway Mucosa and Bone Regeneration and Reconstruction of Maxillary Defects in Rabbits
by Mi Hyun Lim, Jung Ho Jeon, Sun Hwa Park, Byeong Gon Yun, Seok-Won Kim, Dong-Woo Cho, Jeong Hak Lee, Do Hyun Kim and Sung Won Kim
Medicina 2024, 60(12), 2111; https://doi.org/10.3390/medicina60122111 - 23 Dec 2024
Abstract
Background and Objectives: Current craniofacial reconstruction surgical methods have limitations because they involve facial deformation. The craniofacial region includes many areas where the mucosa, exposed to air, is closely adjacent to bone, with the maxilla being a prominent example of this structure. [...] Read more.
Background and Objectives: Current craniofacial reconstruction surgical methods have limitations because they involve facial deformation. The craniofacial region includes many areas where the mucosa, exposed to air, is closely adjacent to bone, with the maxilla being a prominent example of this structure. Therefore, this study explored whether human neural-crest-derived stem cells (hNTSCs) aid bone and airway mucosal regeneration during craniofacial reconstruction using a rabbit model. Materials and Methods: hNTSCs were induced to differentiate into either mucosal epithelial or osteogenic cells in vitro. hNTSCs were seeded into polycaprolactone scaffold (three-dimensionally printed) that were implanted into rabbits with maxillary defects. Four weeks later, tissue regeneration was analyzed via histological evaluation and immunofluorescence staining. Results: In vitro, hNTSCs differentiated into both mucosal epithelial and osteogenic cells. hNTSC differentiation into respiratory epithelial cells was confirmed by Alcian Blue staining, cilia in SEM, and increased expression levels of FOXJ1 and E-cadherin through quantitative RT-PCR. hNTSC differentiation into bone was confirmed by Alizarin Red staining, increased mRNA expression levels of BMP2 (6.1-fold) and RUNX2 (2.3-fold) in the hNTSC group compared to the control. Four weeks post-transplantation, the rabbit maxilla was harvested, and H&E, SEM, and immunohistofluorescence staining were performed. H&E staining and SEM showed that new tissue and cilia around the maxillary defect were more prominent in the hNTSC group. Also, the hNTSCs group showed positive immunohistofluorescence staining for acetylated α-tubulin and cytokerin-5 compared to the control group. Conclusions: hNTSCs combined with PCL scaffold enhanced the regeneration of mucosal tissue and bone in vitro and promoted mucosal tissue regeneration in the in vivo rabbit model. Full article
(This article belongs to the Special Issue New Insights into Plastic and Reconstructive Surgery)
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<p>Differentiation of hNTSCs into epithelial cells. (<b>A</b>) Alcian Blue staining revealing mucus production. Scale bars: 100 µm (<b>B</b>) SEM of cilia. Scale bars: 1.0 µm. (<b>C</b>) Real-time PCR data derived on days 0 and 45 after epithelial differentiation were induced. Bars: Relative expression levels (±SDs). * <span class="html-italic">p</span> &lt; 0.05.</p>
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<p>Cell seeding into artificial maxillary grafts and pre-implantation culture. (<b>A</b>) hNTSC seeding into AMG in a spinner flask. hNTSC sheets covered the AMG after 3 days of culture in osteogenic induction medium before implantation of AMG-hNTSCs into rabbits. (<b>B</b>) An optical microscopic image of AMG seeded with hNTSCs after 3 days of culture (upper panel) and a confocal microscope image (with z-stack projections) after staining for F-actin (red). The nuclei were stained with DAPI (blue). Scale bars: 200 and 100 µm, respectively. (<b>C</b>) Images of CTRL (non-induced A-hNTSCs) and A-hNTSCs stained with Alizarin Red S, a dye used to detect calcium deposition, after 21 days of incubation in osteogenic differentiation medium. (<b>D</b>) The mineralization was quantified by extraction of Alizarin Red S dye using the CPC extraction method, and absorbance was measured at 570 nm. * <span class="html-italic">p</span> &lt; 0.05 compared with CTRL group. (<b>E</b>) The expression levels of BMP2 and RUNX2 after 21 days of incubation in osteogenic differentiation medium as revealed by real-time PCR. Bars: Relative expression levels (±SDs). ** <span class="html-italic">p</span> &lt; 0.01 and *** <span class="html-italic">p</span> &lt; 0.001.</p>
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<p>Surgical and sacrifice procedures and evaluation of ciliary regeneration. (<b>A</b>) Images taken during surgery (<b>top</b>) and sacrifice (<b>bottom</b>). (<b>B</b>) H&amp;E staining of paraffin-embedded sections (scale bars: 1000 µm and 100 µm, respectively), and (<b>C</b>) SEM images obtained at 4 weeks after implantation of AMG or A-hNTSCs. Scale bars: 10 µm.</p>
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<p>Immunohistofluorescence staining of hNTSCs in maxillary defects after implantation of AMG or A-hNTSCs. Confocal microscopy images (z-stack projections) of AMG and A-hNTSCs after staining of paraffin-embedded sections (a) with an antibody against (<b>A</b>) HuNu and (<b>B</b>) double-staining with antibodies against acetylated α-tubulin (green) and cytokeratin-5 (red) at 4 weeks. The nuclei were labeled with DAPI (blue). Scale bars: (<b>A</b>,<b>B</b>): upper panels 50 µm; lower panels 20 µm.</p>
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13 pages, 5886 KiB  
Article
The Influence of Physiological Blood Clot on Osteoblastic Cell Response to a Chitosan-Based 3D Scaffold—A Pilot Investigation
by Natacha Malu Miranda da Costa, Hilary Ignes Palma Caetano, Larissa Miranda Aguiar, Ludovica Parisi, Benedetta Ghezzi, Lisa Elviri, Leonardo Raphael Zuardi, Paulo Tambasco de Oliveira and Daniela Bazan Palioto
Biomimetics 2024, 9(12), 782; https://doi.org/10.3390/biomimetics9120782 - 21 Dec 2024
Viewed by 500
Abstract
Background: The use of ex vivo assays associated with biomaterials may allow the short-term visualization of a specific cell type response inserted in a local microenvironment. Blood is the first component to come into contact with biomaterials, providing blood clot formation, being substantial [...] Read more.
Background: The use of ex vivo assays associated with biomaterials may allow the short-term visualization of a specific cell type response inserted in a local microenvironment. Blood is the first component to come into contact with biomaterials, providing blood clot formation, being substantial in new tissue formation. Thus, this research investigated the physiological blood clot (PhC) patterns formed in 3D scaffolds (SCAs), based on chitosan and 20% beta-tricalcium phosphate and its effect on osteogenesis. Initially, SCA were inserted for 16 h in rats calvaria defects, and, after that, osteoblasts cells (OSB; UMR-106 lineage) were seeded on the substrate formed. The groups tested were SCA + OSB and SCA + PhC + OSB. Cell viability was checked by MTT and mineralized matrix formation in OSB using alizarin red (ARS). The alkaline phosphatase (ALP) and bone sialoprotein (BSP) expression in OSB was investigated by indirect immunofluorescence (IF). The OSB and PhC morphology was verified by scanning electron microscopy (SEM). Results: The SCA + PhC + OSB group showed greater cell viability (p = 0.0169). After 10 days, there was more mineralized matrix deposition (p = 0.0365) and high ALP immunostaining (p = 0.0021) in the SCA + OSB group. In contrast, BSP was more expressed in OSB seeded on SCA with PhC (p = 0.0033). Conclusions: These findings show the feasibility of using PhC in ex vivo assays. Additionally, its inclusion in the experiments resulted in a change in OSB behavior when compared to in vitro assays. This “closer to nature” environment can completely change the scenario of a study. Full article
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<p>Images showing physiological blood clot (PhC) formation on scaffolds in a critical-size defect in rat calvaria. (<b>A</b>) The scaffold inserted immediately after the defect creation. (<b>B</b>) The scaffold with PhC formed after 16 h.</p>
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<p>(<b>A</b>) Flow cytometry cell population distribution in physiological blood clot (PhC) formed on SCA, varying in size and complexity of cells for CD90/CD45 (<b>A.1</b>), CD44/CD34 (<b>A.2</b>), CD42 (<b>A.3</b>), and CD61 (<b>A.4</b>) in the histograms; (<b>B</b>) Proportion of labelled cells for CD90, CD45, CD34, CD44, CD42, and CD61 on PhC cell surface; (<b>C</b>) Cell viability results by MTT assay, expressed as absorbance at 570 nm; (<b>D</b>) Electron micrographs showing SCA + OSB (<b>D.1</b>), SCA + PhC + OSB (<b>D.2</b>), and SCA + PhC (<b>D.3</b>) at 2000× magnification. In the SCA + OSB group (<b>D.1</b>) the OSB cells (arrow) can be seen on the SCA surface. In the SCA + PhC + OSB group (<b>D.2</b>), there were interactions between OSB cells (arrow) and PhC elements (arrow head), leading to visible extracellular matrix deposition by OSB on PhC (asterisk). The SCA + PhC group (<b>D.3</b>) showing the PhC structure without OSB, with emphasis on white and red blood cells (arrow), inserted in a rich and dense fibrin meshwork (arrowhead), sealing all the SCA pores. Scale: 10 <math display="inline"><semantics> <mo>µ</mo> </semantics></math>m. Significance value: * <span class="html-italic">p</span> &lt; 0.05.</p>
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<p>Mineralization assay at 7 days (<b>A</b>) and 10 days (<b>B</b>). The data on Alizarin red S (ARS) stain were expressed as absorbance at 405 nm. Significance value: * <span class="html-italic">p</span> &lt;0.05.</p>
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<p>Immunofluorescence images obtained at Multiphoton Microscopy showing osteoblastic cells (OSBs) seeded on a scaffold (SCA) without (<b>A</b>–<b>E</b>) and with physiological blood clot (PhC) (<b>G</b>–<b>K</b>). The yellow squares in (<b>A</b>,<b>G</b>) represent the merged fluorescences in (<b>B</b>,<b>H</b>), respectively. Alkaline phosphatase (ALP) was labeled with Alexa Fluor 594 (<b>C</b>,<b>I</b>), bone sialoprotein (BSP) with Alexa Fluor 488 (<b>D</b>,<b>J</b>) and cell nuclei with DAPI (<b>E</b>,<b>K</b>). ALP (<b>F</b>) and BSP (<b>L</b>) immunoexpression between the SCA + OSB and SCA + PhC + OSB groups showed different results. Fluorescence intensity data (<b>F</b>,<b>L</b>) are expressed as arbitrary units of pixel intensity per area, as determined by ImageJ software. Scale bars: 20 <math display="inline"><semantics> <mo>µ</mo> </semantics></math>m in A and G, and 50 <math display="inline"><semantics> <mo>µ</mo> </semantics></math>m in (<b>B</b>–<b>E</b>,<b>H</b>–<b>K</b>). Significance value: * <span class="html-italic">p</span> &lt; 0.05.</p>
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17 pages, 5118 KiB  
Article
Microstructural Analysis of the Human Scapula: Mandibular Bone Tissue Engineering Perspectives
by Ilya L. Tsiklin, Denis S. Bezdenezhnych, Aleksei S. Mantsagov, Alexandr V. Kolsanov and Larisa T. Volova
J. Funct. Biomater. 2024, 15(12), 386; https://doi.org/10.3390/jfb15120386 - 20 Dec 2024
Viewed by 281
Abstract
Mandibular bone defect reconstruction remains a significant challenge for surgeons worldwide. Among multiple biodegradable biopolymers, allogeneic bone scaffolds derived from human sources have been used as an alternative to autologous bone grafts, providing optimal conditions for cell recruitment, adhesion, and proliferation and demonstrating [...] Read more.
Mandibular bone defect reconstruction remains a significant challenge for surgeons worldwide. Among multiple biodegradable biopolymers, allogeneic bone scaffolds derived from human sources have been used as an alternative to autologous bone grafts, providing optimal conditions for cell recruitment, adhesion, and proliferation and demonstrating significant osteogenic properties. This study aims to investigate the bone microstructure of the human scapula as a source for allogeneic bone scaffold fabrication for mandibular tissue engineering purposes. We created color-coded anatomical maps of the scapula and the mandible, reflecting the best anatomical and geometrical match. In this pilot study, we hypothesized a microstructural similarity of these bone structures and evaluated the human scapula’s bone tissue engineering potential for mandibular bone tissue engineering by focusing on the microstructural characteristics. Lyophilized human scapular and mandibular bioimplants were manufactured and sterilized. Experimental bone samples from the scapula’s acromion, coracoid, and lateral border from the mandibular condyle, mandibular angle, and mental protuberance were harvested and analyzed using micro-CT and quantitative morphometric analysis. This pilot study demonstrates significant microstructural qualitative and quantitative intra-group differences in the scapular and mandibular experimental bone samples harvested from the various anatomical regions. The revealed microstructural similarity of the human scapular and mandibular bone samples, to a certain extent, supports the stated hypothesis and, thus, allows us to suggest the human scapula as an alternative off-the-shelf allogeneic scaffold for mandibular reconstruction and bone tissue engineering applications. Full article
(This article belongs to the Special Issue Biomaterials in Bone Reconstruction)
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<p>Lyophilized left scapula (<b>a</b>,<b>b</b>) bioimplant Lyoplast<sup>®</sup> ((<b>a</b>)—posterior view, (<b>b</b>)—lateral view: 1—scapular acromion process (SAP); 2—scapular coracoid process (SCP); 3—scapular lateral border (SLB)) and right hemimandible (<b>c</b>) bioimplant Lyoplast<sup>®</sup>: 1—mandibular condyle (MC); 2—mandibular angle (MA); 3—mental protuberance (MP).</p>
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<p>Anatomical mapping of the human scapula ((<b>a</b>)—posterior view; (<b>b</b>)—anterior view; 1—superior angle, 2—inferior angle, 3—lateral border, 4—coracoid process, 5—acromion, 6—glenoid) and the human mandible (<b>c</b>) with respective color-coded recipient zones: mandibular condyle (MC); mandibular angle (MA); mental protuberance (MP).</p>
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<p>Preparation of the experimental mandibular and scapular bone samples ((<b>a</b>)—mandibular condyle (MC), mandibular angle (MA), mental protuberance (MP); (<b>b</b>)—scapular coracoid process (SCP), scapular acromion process (SAP), scapular lateral border (SLB); (<b>c</b>)—trepan bur and harvested experimental bone sample)).</p>
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<p>Scapular bone samples’ image acquisition, volume rendering, and segmentation ((<b>a</b>,<b>d</b>)—SCP; (<b>b</b>,<b>e</b>)—SAP; (<b>c</b>,<b>f</b>)—SLB)).</p>
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<p>Mandibular bone samples’ image acquisition, volume rendering, and segmentation ((<b>a</b>,<b>d</b>)—SCP; (<b>b</b>,<b>e</b>)—SAP; (<b>c</b>,<b>f</b>)—SLB)).</p>
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<p>Comparative analysis of the trabecular and cortical bone morphometric parameters of the experimental scapular bone samples: (<b>a</b>) trabecular bone volumetric parameters; (<b>b</b>) trabecular bone connectivity parameters; (<b>c</b>) cortical bone parameters.</p>
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<p>Comparative analysis of the trabecular and cortical bone morphometric parameters of the experimental mandibular bone samples: (<b>a</b>) trabecular bone volumetric parameters; (<b>b</b>) trabecular bone connectivity parameters; (<b>c</b>) cortical bone parameters.</p>
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<p>Comparative analysis of the trabecular and cortical bone morphometric parameters of the experimental mandibular bone samples: (<b>a</b>) trabecular bone volumetric parameters; (<b>b</b>) trabecular bone connectivity parameters; (<b>c</b>) cortical bone parameters.</p>
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20 pages, 14428 KiB  
Article
miR-181a/MSC-Loaded Nano-Hydroxyapatite/Collagen Accelerated Bone Defect Repair in Rats by Targeting Ferroptosis Pathway
by Xiongjun Xu, Junming Feng, Tianze Lin, Runheng Liu and Zhuofan Chen
J. Funct. Biomater. 2024, 15(12), 385; https://doi.org/10.3390/jfb15120385 - 20 Dec 2024
Viewed by 245
Abstract
Background: The reparative regeneration of jawbone defects poses a significant challenge within the field of dentistry. Despite being the gold standard, autogenous bone materials are not without drawbacks, including a heightened risk of postoperative infections. Consequently, the development of innovative materials that [...] Read more.
Background: The reparative regeneration of jawbone defects poses a significant challenge within the field of dentistry. Despite being the gold standard, autogenous bone materials are not without drawbacks, including a heightened risk of postoperative infections. Consequently, the development of innovative materials that can surpass the osteogenic capabilities of autologous bone has emerged as a pivotal area of research. Methods: Mesenchymal stem cells (MSCs), known for their multilineage differentiation potential, were isolated from human umbilical cords and transfected with miR-181a. The osteogenic differentiation of miR-181a/MSC was investigated. Then, physicochemical properties of miR-181a/MSC-loaded nano-hydroxyapatite (nHAC) scaffolds were characterized, and their efficacy and underlying mechanism in rat calvarial defect repair were explored. Results: miR-181a overexpression in MSCs significantly promoted osteogenic differentiation, as evidenced by increased alkaline phosphatase activity and expression of osteogenic markers. The miR-181a/MSC-loaded nHAC scaffolds exhibited favorable bioactivity and accelerated bone tissue repair and collagen secretion in vivo. Mechanistic studies reveal that miR-181a directly targeted the TP53/SLC7A11 pathway, inhibiting ferroptosis and enhancing the osteogenic capacity of MSCs. Conclusions: The study demonstrates that miR-181a/MSC-loaded nHAC scaffolds significantly enhance the repair of bone defects by promoting osteogenic differentiation and inhibiting ferroptosis. These findings provide novel insights into the molecular mechanisms regulating MSC osteogenesis and offer a promising therapeutic strategy for bone defect repair. Full article
(This article belongs to the Special Issue Biomaterials in Bone Reconstruction)
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<p>MiR-181a promoted osteogenic differentiation of human umbilical cord MSCs. (<b>A</b>) After transfection with three candidate miRNAs (miR-21a, miR-27a, and miR-181a), Alizarin red staining was used to visualize the calcium nodule granules at Day 14. The blank group did not receive osteogenic induction cocktail treatment. Scale bar: 1 cm. Magnification fold of the microscopic image: 200 fold. (<b>B</b>) Detection of ALP activity after 14 days of osteogenic induction of MSCs after transfection with three indicated miRNAs. (<b>C</b>,<b>D</b>) RT-PCR assay was used to examine the expression levels of COL1A1 (<b>C</b>) and RUNX2 (<b>D</b>) after transfection with three indicated miRNAs. (**, <span class="html-italic">p</span> &lt; 0.01; ***, <span class="html-italic">p</span> &lt; 0.001).</p>
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<p>Physical phase and functional group analysis of miR-181a-MSCs-loaded nHAC scaffold. (<b>A</b>) Fourier-transform infrared spectroscopy of miR-181a-MSCs-nHAC (a) and nHAC (b). The right panel is a partial enlargement of the left panel. (<b>B</b>) X-ray diffraction patterns of the materials miR-181a-MSCs-nHAC (a) and nHAC (b). (<b>C</b>) Raman spectra of miR-181a-MSCs-nHAC (a) and nHAC (b).</p>
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<p>SEM photographs and EDX emission energy spectra of the surfaces of indicated biomaterials. (<b>A</b>) SEM photographs and EDX emission energy spectra of the surfaces of miR-181a-MSCs-nHAC. (<b>B</b>) SEM photographs and EDX emission energy spectra of the surfaces of nHAC. The miR-181a-MSCs were indicated by the red arrows, and clustered nanorods were shown by the green arrows.</p>
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<p>The miR-181a/MSC-loaded nHAC composites significantly enhanced the repair of rat calvarial defects. (<b>A</b>) The micro-CT assay showed 3D reconstruction of cranial defects in rats. (<b>B</b>) The bone volume was calculated at 4 weeks and 8 weeks. (<b>C</b>) The BV/TV ratio was calculated at 4 weeks and 8 weeks. (*, <span class="html-italic">p</span> &lt; 0.05; **, <span class="html-italic">p</span> &lt; 0.01; ***, <span class="html-italic">p</span> &lt; 0.001).</p>
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<p>(<b>A</b>) The miR-181a/MSC-loaded nHAC composites accelerated the bone tissue repair. The H&amp;E staining was performed at 4 weeks post-surgery in rats. Black star indicates newly formed bone. Letter M indicates collagen fiber. Arrow indicates microvessel. (<b>B</b>) The miR-181a/MSC-loaded nHAC composites accelerated the bone tissue repair. The H&amp;E staining was performed at 8 weeks post-surgery in rats. Black star indicates newly formed bone. Letter M indicates collagen fiber. Arrow indicates microvessel.</p>
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<p>(<b>A</b>) The miR-181a/MSC-loaded nHAC composites accelerated the bone tissue repair. The H&amp;E staining was performed at 4 weeks post-surgery in rats. Black star indicates newly formed bone. Letter M indicates collagen fiber. Arrow indicates microvessel. (<b>B</b>) The miR-181a/MSC-loaded nHAC composites accelerated the bone tissue repair. The H&amp;E staining was performed at 8 weeks post-surgery in rats. Black star indicates newly formed bone. Letter M indicates collagen fiber. Arrow indicates microvessel.</p>
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<p>(<b>A</b>) The miR-181a/MSC-loaded nHAC composites accelerated collagen secretion. The Masson staining was performed at 4 weeks post-surgery in rats. Black star indicates newly formed bone. Letter M indicates collagen fiber. Arrow indicates microvessel. (<b>B</b>) The miR-181a/MSC-loaded nHAC composites accelerated collagen secretion. The Masson staining was performed at 8 weeks post-surgery in rats. Black star indicates newly formed bone. Letter M indicates collagen fiber. Arrow indicates microvessel.</p>
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<p>(<b>A</b>) The miR-181a/MSC-loaded nHAC composites accelerated collagen secretion. The Masson staining was performed at 4 weeks post-surgery in rats. Black star indicates newly formed bone. Letter M indicates collagen fiber. Arrow indicates microvessel. (<b>B</b>) The miR-181a/MSC-loaded nHAC composites accelerated collagen secretion. The Masson staining was performed at 8 weeks post-surgery in rats. Black star indicates newly formed bone. Letter M indicates collagen fiber. Arrow indicates microvessel.</p>
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<p>(<b>A</b>) The miR-181a/MSC-loaded nHAC composites accelerated bone regeneration. The Goldner’s trichrome staining was performed at 4 weeks post-surgery in rats. Black star indicates newly formed bone. Letter M indicates collagen fiber. Arrow indicates microvessel. (<b>B</b>) The miR-181a/MSC-loaded nHAC composites accelerated bone regeneration. The Goldner’s trichrome staining was performed at 8 weeks post-surgery in rats. Black star indicates newly formed bone. Letter M indicates collagen fiber. Arrow indicates microvessel.</p>
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<p>(<b>A</b>) The miR-181a/MSC-loaded nHAC composites accelerated bone regeneration. The Goldner’s trichrome staining was performed at 4 weeks post-surgery in rats. Black star indicates newly formed bone. Letter M indicates collagen fiber. Arrow indicates microvessel. (<b>B</b>) The miR-181a/MSC-loaded nHAC composites accelerated bone regeneration. The Goldner’s trichrome staining was performed at 8 weeks post-surgery in rats. Black star indicates newly formed bone. Letter M indicates collagen fiber. Arrow indicates microvessel.</p>
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<p>The miR-181a targeted TP53-mediated ferroptosis signaling pathway. (<b>A</b>) After transfection with miR-181a in MSCs, RNA-seq data revealed that miR-181a down-regulated various signaling pathways, including ferroptosis signaling pathway. (<b>B</b>) RT-PCR was performed to detect the transfection efficiency of miR-181a in MSCs. (<b>C</b>) Overexpression of miR-181a reduced the expression of TP53. (<b>D</b>) Overexpression of miR-181a reduced the protein level of TP53. (<b>E</b>) RT-PCR was performed to detect the expression of SLC7A11 after transfection of miR-181a. (*, <span class="html-italic">p</span> &lt; 0.05).</p>
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<p>The miR-181a promoted cell proliferation by inhibiting ROS production. (<b>A</b>) After transfection with miR-181a in MSCs, CCK8 assay revealed that miR-181a enhanced cell proliferation. (<b>B</b>) Flow cytometry assay was performed to detect the cell apoptosis after overexpression of miR-181a in MSCs. (<b>C</b>) Flow cytometry assay showed that overexpression of miR-181a reduced ROS production. (*, <span class="html-italic">p</span> &lt; 0.05; **, <span class="html-italic">p</span> &lt; 0.01).</p>
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<p>The hypothetical model. The miR-181a/MSC-loaded nano-hydroxyapatite/collagen accelerated bone defect repair by targeting TP53-mediated ferroptosis signaling pathway.</p>
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47 pages, 10688 KiB  
Review
A Review of Additive Manufacturing of Biodegradable Fe and Zn Alloys for Medical Implants Using Laser Powder Bed Fusion (LPBF)
by Irene Limón, Javier Bedmar, Juan Pablo Fernández-Hernán, Marta Multigner, Belén Torres, Joaquín Rams and Sandra C. Cifuentes
Materials 2024, 17(24), 6220; https://doi.org/10.3390/ma17246220 - 19 Dec 2024
Viewed by 453
Abstract
This review explores the advancements in additive manufacturing (AM) of biodegradable iron (Fe) and zinc (Zn) alloys, focusing on their potential for medical implants, particularly in vascular and bone applications. Fe alloys are noted for their superior mechanical properties and biocompatibility but exhibit [...] Read more.
This review explores the advancements in additive manufacturing (AM) of biodegradable iron (Fe) and zinc (Zn) alloys, focusing on their potential for medical implants, particularly in vascular and bone applications. Fe alloys are noted for their superior mechanical properties and biocompatibility but exhibit a slow corrosion rate, limiting their biodegradability. Strategies such as alloying with manganese (Mn) and optimizing microstructure via laser powder bed fusion (LPBF) have been employed to increase Fe’s corrosion rate and mechanical performance. Zn alloys, characterized by moderate biodegradation rates and biocompatible corrosion products, address the limitations of Fe, though their mechanical properties require improvement through alloying and microstructural refinement. LPBF has enabled the fabrication of dense and porous structures for both materials, with energy density optimization playing a critical role in achieving defect-free parts. Fe alloys exhibit higher strength and hardness, while Zn alloys offer better corrosion control and biocompatibility. In vitro and in vivo studies demonstrate promising outcomes for both materials, with Fe alloys excelling in load-bearing applications and Zn alloys in controlled degradation and vascular applications. Despite these advancements, challenges such as localized corrosion, cytotoxicity, and long-term performance require further investigation to fully harness the potential of AM-fabricated Fe and Zn biodegradable implants. Full article
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<p>Applications of biodegradable metals in the medical devices industry. (<b>a</b>) Schematic diagram of cardiovascular diseases and stent [<a href="#B13-materials-17-06220" class="html-bibr">13</a>]. (<b>b</b>) Common medical devices used for fracture internal fixation Adapted with permission from [<a href="#B14-materials-17-06220" class="html-bibr">14</a>]. 2024 Elsevier. (<b>c</b>) Tissue engineering approach for reconstruction of large bone defects [<a href="#B15-materials-17-06220" class="html-bibr">15</a>].</p>
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<p>PRISMA flow diagram used for reporting systematic reviews [<a href="#B25-materials-17-06220" class="html-bibr">25</a>].</p>
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<p>Scheme from Li et al. showing the LPBF process at hatch distances of 120 μm (<b>a</b>) and 60 μm (<b>b</b>) Reprinted with permission from [<a href="#B35-materials-17-06220" class="html-bibr">35</a>]. 2024 Elsevier.</p>
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<p>Additive manufactured parts: (<b>a</b>) Adapted with permission from [<a href="#B51-materials-17-06220" class="html-bibr">51</a>], 2024, Elsevier (<b>b</b>) [<a href="#B56-materials-17-06220" class="html-bibr">56</a>], (<b>c</b>) Adapted with permission from [<a href="#B53-materials-17-06220" class="html-bibr">53</a>] 2024, Elsevier, (<b>d</b>) Adapted with permission from [<a href="#B54-materials-17-06220" class="html-bibr">54</a>] 2024, Elsevier and (<b>e</b>) [<a href="#B55-materials-17-06220" class="html-bibr">55</a>].</p>
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<p>Parts quality according to <span class="html-italic">E<sub>v</sub></span> and material. Green indicates optimum conditions, red excess of energy, and blue lack of energy [<a href="#B51-materials-17-06220" class="html-bibr">51</a>,<a href="#B52-materials-17-06220" class="html-bibr">52</a>,<a href="#B53-materials-17-06220" class="html-bibr">53</a>,<a href="#B54-materials-17-06220" class="html-bibr">54</a>,<a href="#B55-materials-17-06220" class="html-bibr">55</a>,<a href="#B56-materials-17-06220" class="html-bibr">56</a>].</p>
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<p>Preliminary study of processing parameters for hatch distance of 90 µm. The number at the top left is the relative density (%), the top right is the number of the sample and the number at the bottom left is the energy density (J/mm<sup>3</sup>) [<a href="#B56-materials-17-06220" class="html-bibr">56</a>].</p>
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<p>(<b>a</b>) Processing windows for pure iron (Zone I—Deformation zone, Zone II—Formation zone, Zone III—Zone of poor formation, and Zone IV—Zone of non-forming) versus laser power and scanning speed; Red square: parts manufactured with 100 W of laser power, green asterisks 80 W and blue triangles at 60 W. (<b>b</b>) Density curves of iron parts as a function of the laser power and scanning speed Adapted with permission from [<a href="#B51-materials-17-06220" class="html-bibr">51</a>]. 2024, Elsevier.</p>
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<p>Pure Fe cross-sectional optical micrographs (<b>a-1</b>,<b>b-1</b>) and Fe35Mn SEM images (<b>a-2</b>,<b>b-2</b>) showing the microstructure with BD out-of-plane and in-plane. Adapted with permission from [<a href="#B54-materials-17-06220" class="html-bibr">54</a>]. 2024, Elsevier.</p>
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<p>Top view and longitudinal cross-section of the CAD models of functionally graded Fe scaffold. Adapted with permission from [<a href="#B60-materials-17-06220" class="html-bibr">60</a>]. 2024, Elsevier.</p>
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<p>Corrosion rate of Fe and its alloys. In orange electrochemical tests and in blue immersion tests. Filled symbols correspond to dense parts and empty symbols correspond to scaffolds [<a href="#B52-materials-17-06220" class="html-bibr">52</a>,<a href="#B53-materials-17-06220" class="html-bibr">53</a>,<a href="#B55-materials-17-06220" class="html-bibr">55</a>,<a href="#B60-materials-17-06220" class="html-bibr">60</a>,<a href="#B63-materials-17-06220" class="html-bibr">63</a>,<a href="#B64-materials-17-06220" class="html-bibr">64</a>].</p>
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<p>Circuit for (<b>a</b>) pure iron. Adapted with permission from [<a href="#B52-materials-17-06220" class="html-bibr">52</a>] (2024, Elsevier) and (<b>b</b>) Fe35Mn scaffold. Adapted with permission from [<a href="#B53-materials-17-06220" class="html-bibr">53</a>] 2024, Elsevier.</p>
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<p>Volumetric energy densities (<span class="html-italic">E<sub>v</sub></span>) used for fabricating Zn and Zn alloys parts by LPBF. Green indicates optimum conditions, red excess of energy, and blue lack of energy [<a href="#B33-materials-17-06220" class="html-bibr">33</a>,<a href="#B77-materials-17-06220" class="html-bibr">77</a>,<a href="#B78-materials-17-06220" class="html-bibr">78</a>,<a href="#B79-materials-17-06220" class="html-bibr">79</a>,<a href="#B80-materials-17-06220" class="html-bibr">80</a>,<a href="#B81-materials-17-06220" class="html-bibr">81</a>,<a href="#B82-materials-17-06220" class="html-bibr">82</a>,<a href="#B83-materials-17-06220" class="html-bibr">83</a>,<a href="#B84-materials-17-06220" class="html-bibr">84</a>,<a href="#B85-materials-17-06220" class="html-bibr">85</a>].</p>
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<p>Appearance of LPBF-produced pure Zn parts showing the effect of fluence with (<b>a</b>) coarse particles and (<b>b</b>) fine particles Adapted with permission from [<a href="#B77-materials-17-06220" class="html-bibr">77</a>]. 2024, Elsevier.</p>
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<p>Picture of LPBF cross-sections of Zn-xWE43 bulk samples (<b>a</b>) Zn2WE43, (<b>b</b>) Zn5WE43 and (<b>c</b>) Zn8WE43 Adapted with permission from [<a href="#B80-materials-17-06220" class="html-bibr">80</a>]. 2024, Elsevier.</p>
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<p>Microhardness of high-density Zn and Zn alloy parts manufactured by LPBF [<a href="#B78-materials-17-06220" class="html-bibr">78</a>,<a href="#B80-materials-17-06220" class="html-bibr">80</a>,<a href="#B81-materials-17-06220" class="html-bibr">81</a>,<a href="#B84-materials-17-06220" class="html-bibr">84</a>,<a href="#B85-materials-17-06220" class="html-bibr">85</a>].</p>
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<p>Scanning electron microscopy top view for scaffolds with (<b>a</b>) diamond unit cell, (<b>b</b>) dodecahedron unit cell, (<b>c</b>) octet truss unit cell, (<b>d</b>) FCC unit cell, and (<b>e</b>) 3D Kagome unit cell Reprinted with permission from [<a href="#B86-materials-17-06220" class="html-bibr">86</a>]. 2024, Elsevier.</p>
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<p>Corrosion rate of Zn and its alloys. In orange electrochemical tests, in blue immersion tests. Filled symbols correspond to dense parts and empty symbols correspond to scaffolds [<a href="#B81-materials-17-06220" class="html-bibr">81</a>,<a href="#B82-materials-17-06220" class="html-bibr">82</a>,<a href="#B83-materials-17-06220" class="html-bibr">83</a>,<a href="#B84-materials-17-06220" class="html-bibr">84</a>,<a href="#B85-materials-17-06220" class="html-bibr">85</a>,<a href="#B88-materials-17-06220" class="html-bibr">88</a>,<a href="#B90-materials-17-06220" class="html-bibr">90</a>,<a href="#B91-materials-17-06220" class="html-bibr">91</a>].</p>
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<p>Equivalent electrical circuit for ZnxCe samples Reprinted with permission from [<a href="#B82-materials-17-06220" class="html-bibr">82</a>]. 2024, Elsevier.</p>
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<p>Quantitative viability results of MG-63 cells in extracts of LPBF processed ZnxMg. Data were normalized to the control group. Values were mean ±SD, n = 3, * <span class="html-italic">p</span> &lt; 0.05 between the test group and the pure Zn group Reprinted with permission from [<a href="#B83-materials-17-06220" class="html-bibr">83</a>]. 2024, Elsevier.</p>
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13 pages, 1995 KiB  
Article
Accelerated Aging Effect on the Stability of the 3D-Printed Biodegradable Implant for Bone Defect Repairs
by Agnieszka Gutowska, Paweł Kubiak, Katarzyna Kośla, Bożena Wilbik-Hałgas, Edyta Chmal-Fudali, Agnieszka Kucharska-Jastrząbek and Marcin Henryk Struszczyk
Materials 2024, 17(24), 6218; https://doi.org/10.3390/ma17246218 - 19 Dec 2024
Viewed by 253
Abstract
This article presents an evaluation of the accelerated aging impact on the structural properties of biodegradable PLA/HAp implants produced using 3D printing technology for use in traumatic bone defect repairs in individual patients. The designed biodegradable implants were sterilized with a radiation dose [...] Read more.
This article presents an evaluation of the accelerated aging impact on the structural properties of biodegradable PLA/HAp implants produced using 3D printing technology for use in traumatic bone defect repairs in individual patients. The designed biodegradable implants were sterilized with a radiation dose of 25 ± 0.99% kGy, then exposed to an accelerated aging process. Selected physicomechanical and chemical properties of biodegradable implants were evaluated with FT-IR spectra analyses and DSC. The accelerated aging process, carried out according to the ASTM F 1980:2002 “Standard Guide for Accelerated Aging of Sterile Barrier Systems and Medical Devices”, simulates three years of implant usage. It confirmed the stability of structural, physical and mechanical properties and proved the effectiveness and safety of the implants’ application. The present study was conducted to determine the shelf-life of newly developed biodegradable implants proposed for the treatment of children and adolescents where bone growth still occurs by using accelerated aging methodologies, allowing the assessment of changes in performance that do not result in a negative impact on the safety of the medical device. Full article
(This article belongs to the Section Biomaterials)
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<p>Implant model made by 3D printing from PLDLA filament: (<b>a</b>) sphere model (top and bottom view), (<b>b</b>) implant dimensions.</p>
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<p>Packaging system prototype for implant.</p>
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<p>FT-IR spectra of an implant after radiation sterilization with a dose of untreated 25 kGy and subjected to accelerated aging, simulating 3 years of storage in real conditions.</p>
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<p>DSC curve of the implant after radiation sterilization at a dose of 25 kGy, unaged and subjected to accelerated aging, simulating 3 years of storage in real conditions.</p>
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<p>Thickness of implant before and after accelerated aging.</p>
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<p>Areal density of implant samples before and after accelerated aging.</p>
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<p>Apparent density of implant before and after accelerated aging.</p>
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<p>Rounding height of implant before and after accelerated aging.</p>
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<p>Deflection for spherical surface implant before and after accelerated aging.</p>
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21 pages, 1533 KiB  
Article
Treatment of High-Grade Chronic Osteomyelitis and Nonunions with PerOssal®: A Retrospective Analysis of Clinical Efficacy and Patient Perspectives
by Jonas Armbruster, Florian Bussmann, Holger Freischmidt, Gregor Reiter, Paul Alfred Gruetzner and Jan Siad El Barbari
J. Clin. Med. 2024, 13(24), 7764; https://doi.org/10.3390/jcm13247764 - 19 Dec 2024
Viewed by 265
Abstract
Background/Objectives: Traditional autologous bone grafts as a treatment for bone defects have drawbacks like donor-site morbidity and limited supply. PerOssal®, a ceramic bone substitute, may overcome those drawbacks and could offer additional benefits like prolonged, local antibiotic release. This study [...] Read more.
Background/Objectives: Traditional autologous bone grafts as a treatment for bone defects have drawbacks like donor-site morbidity and limited supply. PerOssal®, a ceramic bone substitute, may overcome those drawbacks and could offer additional benefits like prolonged, local antibiotic release. This study investigates the clinical and radiological outcomes, including patient-reported outcomes, of using PerOssal® in nonunions (NU) and high-grade chronic osteomyelitis (COM). Methods: A single-center, retrospective study, investigating patients treated with PerOssal® between January 2020 and December 2023. Collected data include patient characteristics as well as various surgical and outcome parameters including the Lower Extremity Functional Scale (LEFS). Results: A total of 82 patients were analyzed. Reinfection occurred in 19.5% of cases. Osseous integration of PerOssal® was achieved in 89% of cases, higher in cavitary defects (91.5%) than segmental defects (72.7%). The revision rate was 32.9%, mainly due to wound healing disorders and reinfections. Mean LEFS score was 53.4 which was heavily influenced by sex (male: 50.7 vs. female: 63.4), revision surgery (no: 55.7 vs. yes: 49.1), reinfection (no: 56.6 vs. yes: 39.4), and osseous integration of PerOssal® (yes: 55.8 vs. no: 38.4). Conclusions: PerOssal® demonstrates promising outcomes in treating NUs and high-grade COM, especially in cavitary defects, with high osseous integration rates and acceptable functional results. However, reinfection remains a concern, particularly with difficult-to-treat pathogens and extensive surgical histories. Early, comprehensive surgical intervention and tailored antibiotic strategies are essential. Patient selection, defect characteristics, and comorbidities significantly influence success. Further research is needed to optimize treatment protocols. Full article
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<p>LEFS Outcome measurement: (<b>a</b>) mean LEFS score for all localizations (53.4 ± 2.5) and specific localizations of the lower extremity or pelvis. No statistically significant difference was observed; (<b>b</b>) analysis for main drivers for worse LEFS via linear regression showed highest differences in dependence on sex, infection, revision, and failed integration. Accordingly, direct comparison of LEFS showed significantly worse LEFS scores for male patients, patients who had reinfection, or in whom integration of the bone substitute failed. Revision in general lowered the LEFS score but statistical analysis remained non-significant. Medians are the black horizontal lines; interquartile range is the height of the rectangle; minimum and maximum value are the whiskers. LEFS: Lower Extremity Functional Scale; ns = not significant, * = <span class="html-italic">p</span> &lt; 0.05.</p>
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<p>Analysis of reinfection: (<b>a</b>) percentage of reinfection in general and split up in between different initial diagnoses; (<b>b</b>) influence of chronic kidney disease on reinfection rate; (<b>c</b>) infection rate in different localizations; (<b>d</b>) mean previous surgeries in patients without and with reinfection. CKD is chronic kidney disease, COM is chronic osteomyelitis, SNU is septic nonunion, ANU is aseptic nonunion; ns = not significant, * = <span class="html-italic">p</span> &lt; 0.05.</p>
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<p>Analysis of revision: (<b>a</b>) percentage breakdown of reasons for revision surgeries in general and categorized by the presence or absence of reinfection; (<b>b</b>) impact of bacterial testing on revision rate; (<b>c</b>) Kaplan–Meier survival analysis of PerOssal<sup>®</sup>; (<b>d</b>) average time between index surgery and first revision for different complications; (<b>e</b>) correlation between the number of revision surgeries and the time between the index surgery and the first revision. Black lines indicate linear regression with 95% confidence intervals. WHD is wound healing disorder; ns = not significant; * = <span class="html-italic">p</span> &lt; 0.05.</p>
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<p>Analysis of integration of PerOssal<sup>®</sup> in cavitary defects or consolidation of nonunions after usage of PerOssal<sup>®</sup> in segmental defects: (<b>a</b>) overall percentage across all analyzed patients; (<b>b</b>) percentage in cavitary compared to segmental defects; (<b>c</b>) percentage in patients with and without reinfection. *** = <span class="html-italic">p</span> &lt; 0.001.</p>
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23 pages, 1894 KiB  
Review
3D Bioprinting in Limb Salvage Surgery
by Iosif-Aliodor Timofticiuc, Serban Dragosloveanu, Ana Caruntu, Andreea-Elena Scheau, Ioana Anca Badarau, Nicolae Dragos Garofil, Andreea Cristiana Didilescu, Constantin Caruntu and Cristian Scheau
J. Funct. Biomater. 2024, 15(12), 383; https://doi.org/10.3390/jfb15120383 - 19 Dec 2024
Viewed by 536
Abstract
With the development of 3D bioprinting and the creation of innovative biocompatible materials, several new approaches have brought advantages to patients and surgical teams. Increasingly more bone defects are now treated using 3D-bioprinted prostheses and implementing new solutions relies on the ability of [...] Read more.
With the development of 3D bioprinting and the creation of innovative biocompatible materials, several new approaches have brought advantages to patients and surgical teams. Increasingly more bone defects are now treated using 3D-bioprinted prostheses and implementing new solutions relies on the ability of engineers and medical teams to identify methods of anchoring 3D-printed prostheses and to reveal the potential influence of bioactive materials on surrounding tissues. In this paper, we described why limb salvage surgery based on 3D bioprinting is a reliable and effective alternative to amputations, and why this approach is considered the new standard in modern medicine. The preliminary results of 3D bioprinting in one of the most challenging fields in surgery are promising for the future of machine-based medicine, but also for the possibility of replacing various parts from the human body with bioactive-based constructs. In addition, besides the materials and constructs that are already tested and applied in the human body, we also reviewed bioactive materials undergoing in vitro or in vivo testing with great potential for human applications in the near future. Also, we explored the recent advancements in clinically available 3D-bioprinted constructs and their relevance in this field. Full article
(This article belongs to the Special Issue Medical Application of Functional Biomaterials (2nd Edition))
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<p>Roadmap of limb salvage surgery approaches, limitations, unmet needs, and the perspectives of 3D printing in improved personalized patient care. ↑ = increased/enhanced.</p>
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<p>Three-dimensional printing constructs can serve as accessories in various orthopedic surgeries or as the main components in limb salvage surgery where 3D bioprinting is used to create entire bone prostheses. Created in BioRender. Timofticiuc, I. (2024) BioRender.com/w87n517, date of last access—12 October 2024.</p>
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<p>Electron Beam Melting (EBM) is the most frequently used technology for 3D printing metals such as titanium or tantalum. After the metal is processed in powder form, a special component distributes the powder as a thin layer at the top of the construction where an electron beam melts it, forming a new layer according to CAD software instructions.</p>
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<p>Illustration of a design that could be used for creating anchoring points in total bone prostheses. Created in BioRender. Timofticiuc, I. (2024) BioRender.com/q54g477, date of last access—12 October 2024.</p>
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22 pages, 12960 KiB  
Article
Fluorinated Porcine Bone-Derived Hydroxyapatite Promotes Vascularized Osteogenesis by Coordinating Human Bone Marrow Mesenchymal Stem Cell/Human Umbilical Vein Endothelial Cell Complexes
by Xiayi Wu, Chunxin Xu, Junming Feng, Shiyu Wu, Runheng Liu, Wei Qiao, Xin Luo, Shoucheng Chen, Zhipeng Li and Zhuofan Chen
Bioengineering 2024, 11(12), 1287; https://doi.org/10.3390/bioengineering11121287 - 18 Dec 2024
Viewed by 348
Abstract
Biogenic hydroxyapatite is known for its osteoinductive potential due to its similarity to human bone and biocompatibility, but insufficient vascularization compared to autogenous bone during early implantation limits bone integration and osteogenesis. Fluorine has been shown to improve hydroxyapatite’s mechanical properties and the [...] Read more.
Biogenic hydroxyapatite is known for its osteoinductive potential due to its similarity to human bone and biocompatibility, but insufficient vascularization compared to autogenous bone during early implantation limits bone integration and osteogenesis. Fluorine has been shown to improve hydroxyapatite’s mechanical properties and the coupling of osteogenic and angiogenic cells. In this study, fluorine-modified biogenic hydroxyapatite (FPHA) with varying fluorine concentrations was prepared and tested for its ability to promote vascularized osteogenesis. FPHA prepared in this study retained the natural porous structure of biological cancellous bone and released F ions when immersed in cell culture medium. The extraction solutions of FPHA0.25 and FPHA0.50 promoted the formation of capillary-like tubes by human umbilical vein endothelial cells (HUVECs), with FPHA0.25 significantly upregulating vegf mRNA and VEGF protein levels in co-cultured human bone marrow mesenchymal stem cells (HBMSCs). Additionally, FPHA0.25 and FPHA0.50 upregulated pdgf-bb mRNA and PDGF-BB protein levels in HUVECs. In vivo experiments using a rabbit cranial defect model demonstrated that FPHA0.25 promoted early bone formation and angiogenesis in the defect area, enhanced VEGF secretion, and increased PDGFR-β expression in endothelial and mesenchymal cells. These findings suggest that fluorine-modified biogenic hydroxyapatite with an optimal fluorine concentration (FPHA0.25) may offer a promising strategy to enhance the body’s innate bone-healing potential by accelerating vascularization. Full article
(This article belongs to the Section Regenerative Engineering)
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<p>Preparation and physicochemical characterization of PHA and FPHA. (<b>A</b>) Preparation of bone blocks; (<b>B</b>,<b>C</b>) Morphological observation of bone blocks under a stereomicroscope; (<b>D</b>–<b>F</b>) Pore analysis of PHA and FPHA; (<b>G</b>) The ion concentration analysis of PHA and FPHA extracts. *: significant difference vs. control (<span class="html-italic">p</span> &lt; 0.05). **: very significant difference vs. control (<span class="html-italic">p</span> &lt; 0.01).</p>
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<p>Optical images (at 50× magnification) of the in vitro angiogenesis assay of cells cultured on Matrigel in the presence of 10% PHA, FPHA0.25, FPHA0.50, and FPHA0.75 extracts for 4 h. (<b>A</b>) HUVECs alone; (<b>B</b>) HUVECs co-cultured with HBMSCs. Quantitative evaluation for tube formation after being cultured on Matrigel for 4 h in the presence of the extracts of PHA, FPHA0.25, FPHA0.50, and FPHA0.75: (<b>C</b>) Covered area; (<b>D</b>) Total tube length; (<b>E</b>) Total loops; (<b>F</b>) Total tubes; *: significant difference vs. control (<span class="html-italic">p</span> &lt; 0.05).</p>
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<p>Influence of FPHA extract on the gene expression and secretory profile of HBMSCs and HUVECs in a co-culture model. (<b>A</b>) ELISA analysis of concentrations of VEGF-a in the supernatant of the co-cultured HBMSCs and HUVECs; (<b>B</b>) Concentrations of PDGF-BB in the supernatant of the co-cultured HBMSCs and HUVECs; (<b>C</b>) Expressions of the angiogenesis-related genes (<span class="html-italic">vegf</span> and its receptor kdr, <span class="html-italic">pdgf-bb</span> and its receptor <span class="html-italic">pdgfr-β</span> co-cultured with extracts of PHA, FPHA0.25, FPHA0.50, and FPHA0.75 for 24 h; (<b>D</b>) Western blot analysis of the co-cultured HBMSCs and HUVECs confirmed that both PDGFRβ and phosphorylation-PDGFRβ were present with or without extracts of FPHA (PHA, FPHA0.25, FPHA0.50, or FPHA0.75). *: significant difference vs. control (<span class="html-italic">p</span> &lt; 0.05).</p>
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<p>The surgical procedures: (<b>A</b>–<b>G</b>) The parietal bone was divided into four quadrants by the sagittal and coronal sutures (<b>C</b>) The schematic diagram of circular bone defect preparation divides the calvarial bone into four quadrants using the sagittal (a) and coronal sutures. The sites are labeled sequentially as ① (left anterior), ② (right anterior), ③ (left posterior), and ④ (right posterior). (<b>D</b>) in which a 7 mm diameter circular full-thickness defect was prepared; (<b>E</b>) defects were filled with bone graft material in accordance with the original anatomical shape of the skull; (<b>F</b>,<b>G</b>) covered and fixed implant material by the bilateral periosteum subcutaneous tissues and sutured the skin. Schematic diagram showing the animal and grafted defect groups. (<b>H</b>) Detailed grouping and experimental plan for the animal study.</p>
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<p>Micro-CT evaluation of bone formation in the cranial defect region of rabbits. (<b>A</b>) Three-dimensional reconstruction of rabbit calvarial bone defects ((<b>a</b>,<b>b</b>,<b>i</b>,<b>j</b>) were blank controls; (<b>c</b>,<b>d</b>,<b>k</b>,<b>l</b>) defects were grafted with PHA; (<b>e</b>,<b>f</b>,<b>m</b>,<b>n</b>) FPHA0.25; (<b>g</b>,<b>h</b>,<b>o</b>,<b>p</b>) FPHA0.50 granules; the upper two columns represented 6 w post-surgery and the lower two columns represented 16 w post-surgery). (<b>B</b>) Bone volume over total tissue volume (%) and (<b>C</b>). The percentage of new bone formation (%) within the bone defect of the blank control, PHA, FPHA0.25, and FPHA0.50 at 6 weeks and 16 weeks post-surgery. (* indicated <span class="html-italic">p</span> &lt; 0.05).</p>
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<p>H&amp;E staining for the decalcified sections of PHA, FPHA0.25, and FPHA0.50 implanted into calvarial defects of rabbits for 2, 6, and 16 weeks. (<b>A</b>) Photomicrographs at 200× magnification. (<b>B</b>) Microvessel density analysis after 2 w, 6 w, and 16 w post-implantation, * significant difference vs. blank control (<span class="html-italic">p</span> &lt; 0.05).</p>
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<p>Representative photomicrographs of IHC staining. (<b>A</b>,<b>B</b>), respectively, show the VEGF and PDGFR-β distribution in the decalcified sections of the rabbit calvarial defects for 2, 6, and 16 weeks: the blank defect without grafting materials and defects grafted with PHA, FPHA0.25, FPHA0.50, and FPHA0.75. (<b>C</b>,<b>D</b>) Quantitative analysis for angiogenic factors VEGF and PDGFR-β present in the FPHA grafted calvaria defect of rabbits for 2, 6, and 16 weeks. * significant difference vs. blank control (<span class="html-italic">p</span> &lt; 0.05).</p>
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12 pages, 3024 KiB  
Article
The Effect of Bone Glue on the Performance of Traditional Painted Furniture Ground Layers
by Yushu Chen, Wangyu Xu, Tong Chen and Jianan Wang
Coatings 2024, 14(12), 1585; https://doi.org/10.3390/coatings14121585 - 18 Dec 2024
Viewed by 293
Abstract
This research investigates how the inclusion of bone glue affects the performance of traditional painted furniture ground layers, particularly under dry–wet cycling conditions. The ground layers, applied to wood substrates in seven different ratios of bone glue to gypsum powder (10%, 20%, 30%, [...] Read more.
This research investigates how the inclusion of bone glue affects the performance of traditional painted furniture ground layers, particularly under dry–wet cycling conditions. The ground layers, applied to wood substrates in seven different ratios of bone glue to gypsum powder (10%, 20%, 30%, 40%, 50%, and 60%), were tested for mass changes, dimensional stability, adhesion, and surface roughness. The results showed that higher bone glue content (especially 50% and 60%) led to improved stability, reduced mass fluctuations, and better dimensional stability. The 50% bone glue sample exhibited the best overall stability with minimal weight change (<1.6%) and reduced shrinkage. Adhesion strength increased with bone glue content, reaching 3.48 MPa at 60% bone glue. Lower bone glue content resulted in poor adhesion and visible defects such as cracking and blistering. SEM analysis confirmed that higher bone glue content enhanced bonding between the ground layer and the wood substrate. Full article
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<p>Schematic diagram of the dry–wet cycling test apparatus.</p>
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<p>Visual aspects of the control group and ground layer after 5 cycles of dry–wet cycling.</p>
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<p>Percentage change in weight of samples during dry–wet cycling.</p>
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<p>Radial dimension change in samples during dry–wet cycling.</p>
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<p>Tangential dimension change in samples during dry–wet cycling.</p>
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<p>Samples’ adhesion strength changes after dry–wet cycling.</p>
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<p>Surface roughness of ground layer after dry–wet cycling.</p>
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<p>SEM micrographs of the interface between the ground layer and wood in the radial section for samples S2, S4, and S6, before and after dry–wet treatment (the arrows indicate prominent cracks at the interface).</p>
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9 pages, 2014 KiB  
Article
Osteogenesis and Embryogenesis in Zebrafish Embryo Is Differentially Modulated by Solvents and Prednisolone
by Marta Carnovali, Giuseppe Banfi and Massimo Mariotti
Fishes 2024, 9(12), 519; https://doi.org/10.3390/fishes9120519 - 18 Dec 2024
Viewed by 341
Abstract
Several molecules and extracts are known to have bone-specific effects. For example, the long-term use of glucocorticoids like prednisolone causes several negative effects including a loss of bone mass. Molecules like prednisolone are usually dissolved in organic solvent which are known to be [...] Read more.
Several molecules and extracts are known to have bone-specific effects. For example, the long-term use of glucocorticoids like prednisolone causes several negative effects including a loss of bone mass. Molecules like prednisolone are usually dissolved in organic solvent which are known to be toxic for zebrafish embryo in certain concentrations. Nevertheless, solvents like dimethyl sulfoxide (DMSO), ethanol and methanol have never been tested for specific skeletal effects during development in dose-dependency. Vitality assay, live fluorescence and bone-specific staining were used to evaluate solvents effects compared to prednisolone. DMSO, ethanol and methanol perturb osteogenesis starting from 1%, 1.5% and 3% respectively, concentrations in which vasculature, length and survival rate appear unaffected. This effect may be due to high sensitivity of the osteogenesis process to external chemical stimuli, especially in the trunk. On the contrary, the negative effect of prednisolone on skeletal development appears more specific since it is found at very low concentrations, far from any other developmental defects. The recommended solvent concentration to be used in zebrafish embryos osteogenesis assay was established in 0.5% for DMSO, 2% for methanol and 0.5% for ethanol. We recommend analyzing both head and trunk mineralization in zebrafish embryo osteogenesis assay. Full article
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<p>Mortality rate of embryos grown under different concentrations evaluated at 5 dpf: (<b>A</b>) DMSO from 0 to 2.5%, (<b>B</b>) PN from 0 to 200 µM (in DMSO from 0 to 0.5%), (<b>C</b>) EtOH from 0 to 2%, (<b>D</b>) MetOH from 0 to 3%. Solvents show mortality at different concentration whereas PN does not (*** <span class="html-italic">p</span> &lt; 0.001; ** <span class="html-italic">p</span> &lt; 0.01; * <span class="html-italic">p</span> &lt; 0.05).</p>
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<p>Length (µm) in 5 dpf embryos grown under different concentrations of PN (in µM) (<b>B</b>) and, expressed in percentage %, of solvents DMSO (<b>A</b>), EtOH (<b>C</b>), MetOH (<b>D</b>). CTR was the untreated control (CTR). 2% DMSO had significant effect on embryo length. (* <span class="html-italic">p</span> &lt; 0.05).</p>
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<p>Blood vessels analysis in untreated control (CTR), 1% DMSO, 10 µM PN, 1% EtOH and 2% MetOH embryos. The fluorescent pattern of vessels does not show any alteration in all the conditions. ISV = inter-segmental vessels, DA = dorsal aorta, CV = cardinal vein.</p>
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<p>Vertebral mineralization rate of 5 dpf embryos grown under no treatment (CTR) or exposed to different concentrations of solvents DMSO (<b>A</b>), EtOH (<b>C</b>), MetOH (<b>D</b>) and PN (<b>B</b>). The number of vertebral bodies (N.V.) was reduced at higher concentration of solvents but at lower concentrations in PN samples * (<span class="html-italic">p</span> &lt; 0.05).</p>
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<p>Zebrafish larvae double stained with alizarin red and alcian blue: whole embryo (left panel), head (central panel) and trunk (right panel). Mineralizing structures can be visualized in purple and cartilage in blue. Black arrow indicates the mineralizing vertebral bodies in the trunk. 5 dpf embryos were grown under 1 and 2% DMSO whereas CTR was untreated. No mineralization can be detected in the trunk of both 1 and 2% DMSO. Head mineralization is defective in 2% DMSO only, where also cartilage and general morphology seems to be altered. M = Merckel’s cartilage, Op = operculum, N = notochord.</p>
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<p>Zebrafish larvae head double stained with alizarin red and alcian blue. Mineralizing structures can be visualized in purple and cartilage in blue. Black arrow indicates the mineralizing vertebral bodies in the trunk. Embryos grown in PN do not show mineralization defects in the head whereas trunk mineralization was reduced in 1 µM (middle panel) and suppressed in 10 µM (lower panel) respect to untreated controls (CTR, upper panel). Cartilage and morphology seem not to be altered. M = Merckel’s cartilage, Op = operculum, N = notochord.</p>
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