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Search Results (1,973)

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Keywords = bone tissue engineering

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15 pages, 10134 KiB  
Article
Investigation of Calcium Phosphate-Based Biopolymer Composite Scaffolds for Bone Tissue Engineering
by Monika Furko, Zsolt E. Horváth, Istvan Tolnai, Katalin Balázsi and Csaba Balázsi
Int. J. Mol. Sci. 2024, 25(24), 13716; https://doi.org/10.3390/ijms252413716 (registering DOI) - 22 Dec 2024
Abstract
We present a novel method for preparing bioactive and biomineralized calcium phosphate (mCP)-loaded biopolymer composite scaffolds with a porous structure. Two types of polymers were investigated as matrices: one natural, cellulose acetate (CA), and one synthetic, polycaprolactone (PCL). Biomineralized calcium phosphate particles were [...] Read more.
We present a novel method for preparing bioactive and biomineralized calcium phosphate (mCP)-loaded biopolymer composite scaffolds with a porous structure. Two types of polymers were investigated as matrices: one natural, cellulose acetate (CA), and one synthetic, polycaprolactone (PCL). Biomineralized calcium phosphate particles were synthesized via wet chemical precipitation, followed by the addition of organic biominerals, such as magnesium gluconate and zinc gluconate, to enhance the bioactivity of the pure CP phase. We compared the morphological and chemical characteristics of the two types of composites and assessed the effect of biomineralization on the particle structure of pure CP. The precipitated CP primarily consisted of nanocrystalline apatite, and the addition of organic trace elements significantly influenced the morphology by reducing particle size. FE-SEM elemental mapping confirmed the successful incorporation of mCP particles into both CA and PCL polymer matrices. Short-term immersion tests revealed that the decomposition rate of both composites is slow, with moderate and gradual ionic dissolution observed via ICP-OES measurements. The weight loss of the PCL-based composite during immersion was minimal, decreasing by only 0.5%, while the CA-based composite initially exhibited a slight weight increase before gradually decreasing over time. Full article
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Figure 1
<p>FE-SEM images of amorphous apatite (CP) (<b>a</b>) biomineralized (Mg, Zn added apatite (mCP) (<b>b</b>), pure cellulose acetate (<b>c</b>), pure PCL polymer (<b>d</b>), as well as their composites CA-mCP (<b>e</b>) and PCL-mCP (<b>f</b>). The parameters used in the preparation were kept consistent to ensure their comparability.</p>
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<p>FE-SEM images of amorphous apatite (CP) (<b>a</b>) biomineralized (Mg, Zn added apatite (mCP) (<b>b</b>), pure cellulose acetate (<b>c</b>), pure PCL polymer (<b>d</b>), as well as their composites CA-mCP (<b>e</b>) and PCL-mCP (<b>f</b>). The parameters used in the preparation were kept consistent to ensure their comparability.</p>
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<p>Scanning electron microscope image and the corresponding elemental mapping of biomineralized (Mg, Zn) calcium apatite.</p>
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<p>Scanning electron microscope image and the corresponding elemental mapping of PCL-mCP composite (<b>a</b>) and CA-mCP composite (<b>b</b>).</p>
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<p>XRD patterns of CP and mCP powders (<b>a</b>) prepared by wet chemical method and the PCL-mCP, CA.mCP composites (<b>b</b>).</p>
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<p>FE-SEM images on CA-mCP (<b>a</b>) and PCL-mCP (<b>c</b>) composites as prepared as well as CA-mCP (<b>b</b>) and PCL-mCP (<b>d</b>) composites after two weeks of immersion in saline solution.</p>
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<p>Sample weight changes during the two-week immersion period in saline solution at room temperature. Values are graphed as the mean ± standard deviation (<span class="html-italic">n</span> = 3). * indicates <span class="html-italic">p</span>  &lt;  0.05; ** indicates <span class="html-italic">p</span> &lt;  0.01.</p>
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<p>Cumulative concentrations of the dissolved bioactive ions from CA-mCP (<b>a</b>) and PCL-mCP (<b>b</b>) composites soaked in saline solution at room temperature. The values are normalized to the unit area of samples. All data points are presented as the mean ± standard deviation (<span class="html-italic">n</span> = 3).</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 262
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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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 510
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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20 pages, 3395 KiB  
Article
Innovative Ink-Based 3D Hydrogel Bioprinted Formulations for Tissue Engineering Applications
by Ana Catarina Sousa, Grace Mcdermott, Fraser Shields, Rui Alvites, Bruna Lopes, Patrícia Sousa, Alícia Moreira, André Coelho, José Domingos Santos, Luís Atayde, Nuno Alves, Stephen M. Richardson, Marco Domingos and Ana Colette Maurício
Gels 2024, 10(12), 831; https://doi.org/10.3390/gels10120831 - 17 Dec 2024
Viewed by 421
Abstract
Three-dimensional (3D) models with improved biomimicry are essential to reduce animal experimentation and drive innovation in tissue engineering. In this study, we investigate the use of alginate-based materials as polymeric inks for 3D bioprinting of osteogenic models using human bone marrow stem/stromal cells [...] Read more.
Three-dimensional (3D) models with improved biomimicry are essential to reduce animal experimentation and drive innovation in tissue engineering. In this study, we investigate the use of alginate-based materials as polymeric inks for 3D bioprinting of osteogenic models using human bone marrow stem/stromal cells (hBMSCs). A composite bioink incorporating alginate, nano-hydroxyapatite (nHA), type I collagen (Col) and hBMSCs was developed and for extrusion-based printing. Rheological tests performed on crosslinked hydrogels confirm the formation of solid-like structures, consistently indicating a superior storage modulus in relation to the loss modulus. The swelling behavior analysis showed that the addition of Col and nHA into an alginate matrix can enhance the swelling rate of the resulting composite hydrogels, which maximizes cell proliferation within the structure. The LIVE/DEAD assay outcomes demonstrate that the inclusion of nHA and Col did not detrimentally affect the viability of hBMSCs over seven days post-printing. PrestoBlueTM revealed a higher hBMSCs viability in the alginate-nHA-Col hydrogel compared to the remaining groups. Gene expression analysis revealed that alginate-nHA-col bioink favored a higher expression of osteogenic markers, including secreted phosphoprotein-1 (SPP1) and collagen type 1 alpha 2 chain (COL1A2) in hBMSCs after 14 days, indicating the pro-osteogenic differentiation potential of the hydrogel. This study demonstrates that the incorporation of nHA and Col into alginate enhances osteogenic potential and therefore provides a bioprinted model to systematically study osteogenesis and the early stages of tissue maturation in vitro. Full article
(This article belongs to the Special Issue Recent Research on Alginate Hydrogels in Bioengineering Applications)
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<p>Rheological experiments with the storage moduli (G′) (shown in black) and loss moduli (G″) (shown in red) of crosslinked alginate and alginate-nHA-Col under a range of conditions. (<b>a</b>) Amplitude sweeps performed at a frequency of 1 Hz. (<b>b</b>) Frequency sweeps performed at an oscillation strain of 0.1%. The evaluations were performed in triplicate.</p>
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<p>Stress–strain curves resulting from compression tests of alginate hydrogel (red) and alginate-nHA-Col hydrogel (black) (<span class="html-italic">n</span> = 3).</p>
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<p>Hydrogel swelling rate from 1 to 72 h. Alg: alginate (red); Alg-nHA-Col (black) (<span class="html-italic">n</span> = 3).</p>
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<p>(<b>A</b>) CAD model designed in BioCAM™ software (version 2.0); (<b>B</b>) 3D generated model; (<b>C</b>) 3D generated model in a 12-well plate; (<b>D</b>) Cell-laden print in the agarose support bath.</p>
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<p>(<b>A</b>) Live/dead staining images of printed hBMSCs in alginate and alginate-nHA-Col after 1, 3, and 7 days in culture. Live cells are stained green and dead cells are stained red. (<b>B</b>) The percentage of cell viability of bioprinted hBMSCs cultured in 2% alginate and 2% alginate-0.5% nHA-0.5% Col for 1, 3, and 7 days (<span class="html-italic">n</span> = 3).</p>
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<p>(<b>A</b>) Corrected absorbance evaluated by Presto Blue<sup>®</sup> viability assay for hBMSCs (<span class="html-italic">n</span> = 3). Result significances are presented through the symbol (*), according to the <span class="html-italic">p</span> value, with * <span class="html-italic">p</span> &lt; 0.05. (<b>B</b>) Percent viability inhibition assay. The results were normalized in relation to the control. The 30% threshold shown (dashed line) represents the inhibition above which the effect is considered cytotoxic (under ISO 10993-5:2009 guidelines).</p>
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<p>Gene expression levels of printed hBMSCs in alginate and alginate-nHA-Col bioinks after 7 and 14 days under osteogenic differentiation: runt-related transcription factor 2 (RUNX2) (<b>A</b>), alkaline phosphatase (ALPL) (<b>B</b>), integrin-binding sialoprotein (IBSP) (<b>C</b>), secreted phosphoprotein-1 (SPP1) (<b>D</b>), and collagen type 1 alpha 2 chain (COL1A2) (<b>E</b>).</p>
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<p>Graphical representation of the preparation of alginate and alginate-nHA-Col-based solutions.</p>
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<p>(<b>A</b>) 3D Discovery Evolution bioprinter; (<b>B</b>) Schematic representation of the pressure-assisted extrusion process, in which pressurized air drives the bioink from the bioprinter cartridge through a needle into a well plate containing a suspension bath.</p>
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16 pages, 4966 KiB  
Article
Polyetheretherketone Double Functionalization with Bioactive Peptides Improves Human Osteoblast Response
by Leonardo Cassari, Cristian Balducci, Grazia M. L. Messina, Giovanna Iucci, Chiara Battocchio, Federica Bertelà, Giovanni Lucchetta, Trevor Coward, Lucy Di Silvio, Giovanni Marletta, Annj Zamuner, Paola Brun and Monica Dettin
Biomimetics 2024, 9(12), 767; https://doi.org/10.3390/biomimetics9120767 - 17 Dec 2024
Viewed by 386
Abstract
In recent years, the demand for orthopedic implants has surged due to increased life expectancy, necessitating the need for materials that better mimic the biomechanical properties of human bone. Traditional metal implants, despite their mechanical superiority and biocompatibility, often face challenges such as [...] Read more.
In recent years, the demand for orthopedic implants has surged due to increased life expectancy, necessitating the need for materials that better mimic the biomechanical properties of human bone. Traditional metal implants, despite their mechanical superiority and biocompatibility, often face challenges such as mismatched elastic modulus and ion release, leading to complications and implant failures. Polyetheretherketone (PEEK), a semi-crystalline polymer with an aromatic backbone, presents a promising alternative due to its adjustable elastic modulus and compatibility with bone tissue. This study explores the functionalization of sandblasted 3D-printed PEEK disks with the bioactive peptides Aoa-GBMP1α and Aoa-EAK to enhance human osteoblast response. Aoa-GBMP1α reproduces 48–69 trait of Bone Morphogenetic Protein 2 (BMP-2), whereas Aoa-EAK is a self-assembling peptide mimicking extracellular matrix (ECM) fibrous structure. Superficial characterization included X-ray photoelectron spectroscopy (XPS), white light interferometer analysis, static water contact angle (S-WCA), and force spectroscopy (AFM-FS). Biological assays demonstrated a significant increase in human osteoblast (HOB) proliferation, calcium deposition, and expression of osteogenic genes (RUNX2, SPP1, and VTN) on functionalized PEEK compared to non-functionalized controls. The findings suggest that dual peptide-functionalized PEEK holds significant potential for advancing orthopedic implant technology. Full article
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<p>3D-printed PEEK disk. Diameter 1 cm, height 0.4 cm.</p>
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<p>Microscope images of 2000 grit paper smooth PEEK (<b>a</b>–<b>c</b>), R60-PEEK (<b>d</b>–<b>f</b>), and R110-PEEK (<b>g</b>–<b>i</b>). Magnification at 6.3× (<b>a</b>,<b>d</b>,<b>g</b>), 12.5× (<b>b</b>,<b>e</b>,<b>h</b>), and 32× (<b>c</b>,<b>f</b>,<b>i</b>).</p>
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<p>PEEK functionalization via oxime formation scheme.</p>
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<p>HOB proliferation test at 7 days after cell seeding. Data are reported as a percentage of CFSE-positive cells. PEEK refers to smooth samples; R60-PEEK and R110-PEEK are samples of PEEK sandblasted with a 60 μm and 110 μm grain size, respectively. Significance levels: * <span class="html-italic">p</span>-value &lt; 0.05, ** <span class="html-italic">p</span>-value &lt; 0.01, *** <span class="html-italic">p</span>-value &lt; 0.0001.</p>
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<p>Qualitative evaluation of drop dispersion on PEEK disks of (<b>a</b>) water, (<b>b</b>) 50% DMF/MilliQ water, (<b>c</b>) 50% DMSO/MilliQ water, and (<b>d</b>) DMSO.</p>
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<p>C1s, N1s, and O1s XPS spectra and relative curve-fitting analysis of sample PEEK + Aoa-EAK (<b>a</b>) in 1 eq of AcOH in DMSO and (<b>b</b>) in 40 mM monobasic sodium phosphate at pH 6; markers represent experimental points, lines fitting components, and calculated spectra.</p>
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<p>WCA results on R110-PEEK and R110-PEEK enriched with Aoa-GBMP1α and Aoa-EAK simultaneously.</p>
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<p>(<b>a</b>) Young’s Modulus and (<b>b</b>) force adhesion of untreated smooth PEEK and R110-PEEK enriched with Aoa-GBMP1α and Aoa-EAK simultaneously.</p>
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<p>(<b>a</b>) AlamarBlueTM data obtained at days 1 and 7 following HOB seeding, (<b>b</b>) Alizarin Red assay for evaluating calcium deposition after 7 days, and (<b>c</b>) qRT-PCR analysis performed to evaluate the expression of <span class="html-italic">RUNX2</span>, <span class="html-italic">SPP1</span>, and <span class="html-italic">VTN</span> genes 1 day post-seeding with HOB on smooth PEEK and R110-PEEK + Aoa-GBMP1α + Aoa-EAK samples. Statistical significance: **** <span class="html-italic">p</span>-value &lt; 0.0001.</p>
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19 pages, 7699 KiB  
Article
Development of New Chitosan-Based Complex with Bioactive Molecules for Regenerative Medicine
by Natasha Maurmann, Gabriela Moraes Machado, Rafaela Hartmann Kasper, Marcos do Couto, Luan Paz, Luiza Oliveira, Juliana Girón Bastidas, Paola Arosi Bottezini, Lucas Machado Notargiacomo, Carlos Arthur Ferreira, Luciano Pighinelli, Caren Serra Bavaresco, Patricia Pranke and Myrian Brew
Future Pharmacol. 2024, 4(4), 873-891; https://doi.org/10.3390/futurepharmacol4040046 - 16 Dec 2024
Viewed by 428
Abstract
Background/Objectives: The development of new materials incorporating bioactive molecules for tissue regeneration is a growing area of interest. The objective of this study was to develop a new complex specifically designed for bone and skin tissue engineering, combining chitosan, ascorbic acid-2-magnesium phosphate (ASAP), [...] Read more.
Background/Objectives: The development of new materials incorporating bioactive molecules for tissue regeneration is a growing area of interest. The objective of this study was to develop a new complex specifically designed for bone and skin tissue engineering, combining chitosan, ascorbic acid-2-magnesium phosphate (ASAP), and β-tricalcium phosphate (β-TCP). Methods: Chitosan and the complexes chitosan/ASAP and chitosan/ASAP/β-TCP were prepared in membrane form, macerated to a particulate format, and then subjected to characterization through Fourier transform infrared (FTIR) spectroscopy, optical and scanning electron microscopy (SEM), zeta potential, thermogravimetric analysis (TGA), and differential scanning calorimetry (DSC). Cell viability was evaluated through a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and with fluorescein diacetate (FDA) and propidium iodide (PI) staining in stem cells obtained from deciduous teeth. Statistical analyses were performed using analysis of variance (ANOVA), followed by Tukey’s test. Results: The FTIR results indicated the characteristic bands in the chitosan group and the complexation between chitosan, ASAP, and β-TCP. Microscopic characterization revealed a polydisperse distribution of micrometric particles. Zeta potential measurements demonstrated a reduction in surface charge upon the addition of ASAP and β-TCP to the chitosan matrix. TGA and DSC analyses further indicated complexation between the three components and the successful formation of a cross-linked structure in the chitosan matrix. Stem cells cultured with the particulate biomaterials demonstrated their biocompatibility. Statistical analysis revealed a significant increase in cell viability for the chitosan/ASAP and chitosan/ASAP/β-TCP groups compared to the chitosan control. Conclusions: Therefore, the chitosan/ASAP complex demonstrated potential for skin regeneration, while the chitosan/ASAP/β-TCP formulation showed promise as a biomaterial for bone regeneration due to the presence of β-tricalcium phosphate. Full article
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<p>Summary of experiments: (<b>a</b>) schematic presentation of the chemical structure and dissolution of chitosan in an aqueous solution of hydrochloric acid; (<b>b</b>) chemical structure and dissolution of L-ascorbic acid 2-phosphate sesquimagnesium salt hydrate (ASAP) in an aqueous solution of hydrochloric acid; (<b>c</b>) chemical structure and dissolution of beta-tricalcium phosphate (β-TCP) in the aqueous solution of hydrochloric acid; (<b>d</b>) filtration; (<b>e</b>) pasty material; (<b>f</b>) dried membrane; (<b>g</b>) particulate biomaterial obtained after maceration; (<b>h</b>) ultraviolet radiation in a laminar hood to reduce the risk of contamination.</p>
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<p>FTIR spectrum of the chitosan particles (Chit), chitosan/ascorbic acid-2-magnesium phosphate complex (Chit/ASAP), and the complex with β-tricalcium phosphate (Chit/ASAP/β-TCP).</p>
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<p>Micrographs of chitosan particles (Chit), chitosan/ascorbic acid-2-magnesium phosphate complex (Chit/ASAP), and the complex with β-tricalcium phosphate (Chit/ASAP/β-TCP): (<b>a</b>) optical microscopy reveals the general morphology of the particles; (<b>b</b>) scanning electron microscopy offers a high-resolution view, highlighting surface details of the particles. The scale bar represents 100 μm, except for in 2000× magnification, which is 10 μm.</p>
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<p>Micrographs of chitosan particles (Chit), chitosan/ascorbic acid-2-magnesium phosphate complex (Chit/ASAP), and the complex with β-tricalcium phosphate (Chit/ASAP/β-TCP): (<b>a</b>) optical microscopy reveals the general morphology of the particles; (<b>b</b>) scanning electron microscopy offers a high-resolution view, highlighting surface details of the particles. The scale bar represents 100 μm, except for in 2000× magnification, which is 10 μm.</p>
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<p>Zeta potential measurement of chitosan particles (Chit), chitosan/ascorbic acid-2-magnesium phosphate complex (Chit/ASAP), and the complex with β-tricalcium phosphate (Chit/ASAP/β-TCP) in 1 mM NaCl: (<b>a</b>) graphical representation with data expressed as mean ± standard deviation. Different letters indicate significant differences (<span class="html-italic">p</span> ≤ 0.05) by ANOVA, followed by Tukey’s test. (<b>b</b>) Distribution.</p>
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<p>Thermogravimetric analysis (TGA) of chitosan particles (Chit), chitosan/ascorbic acid-2-magnesium phosphate complex (Chit/ASAP), and the complex with β-tricalcium phosphate (Chit/ASAP/β-TCP).</p>
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<p>Differential scanning calorimetry (DSC) of chitosan particles (Chit), chitosan/ascorbic acid-2-magnesium phosphate complex (Chit/ASAP), and the complex with β-tricalcium phosphate (Chit/ASAP/β-TCP).</p>
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<p>Biological test with mesenchymal stem cells (MSCs). (<b>a</b>) Fibroblastoid morphology of cells adhered to in vitro culture plastics, and osteogenic, adipogenic, and chondrogenic differentiation of MSCs, stained with alizarin red S, oil red O, and alcian blue, respectively. The scale bar represents 50 μm. Viability of MSCs 3 days after treatment with particles: (<b>b</b>) MTT assay; (<b>c</b>) staining of live/dead cells with fluorescein diacetate and propidium iodide. The scale bar represents 100 μm. The control corresponds to cells grown directly in the wells of the tissue culture plate; Chit, to 10 mg/mL of chitosan; Chit/ASAP, to 10.3 mg/mL of the complex chitosan with ascorbic acid-2-magnesium phosphate; and Chit/ASAP/TCP, to 20.3 mg/mL of the complex Chit/ASAP with β-tricalcium phosphate. Data expressed as mean ± standard error of the mean. * indicates a statistically significant difference (<span class="html-italic">p</span> &lt; 0.05) in relation to the control by ANOVA followed by Tukey’s test.</p>
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<p>Biological test with mesenchymal stem cells (MSCs). (<b>a</b>) Fibroblastoid morphology of cells adhered to in vitro culture plastics, and osteogenic, adipogenic, and chondrogenic differentiation of MSCs, stained with alizarin red S, oil red O, and alcian blue, respectively. The scale bar represents 50 μm. Viability of MSCs 3 days after treatment with particles: (<b>b</b>) MTT assay; (<b>c</b>) staining of live/dead cells with fluorescein diacetate and propidium iodide. The scale bar represents 100 μm. The control corresponds to cells grown directly in the wells of the tissue culture plate; Chit, to 10 mg/mL of chitosan; Chit/ASAP, to 10.3 mg/mL of the complex chitosan with ascorbic acid-2-magnesium phosphate; and Chit/ASAP/TCP, to 20.3 mg/mL of the complex Chit/ASAP with β-tricalcium phosphate. Data expressed as mean ± standard error of the mean. * indicates a statistically significant difference (<span class="html-italic">p</span> &lt; 0.05) in relation to the control by ANOVA followed by Tukey’s test.</p>
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41 pages, 3593 KiB  
Review
Nanocomposites Based on Iron Oxide and Carbonaceous Nanoparticles: From Synthesis to Their Biomedical Applications
by Mirela Văduva, Andreea Nila, Adelina Udrescu, Oana Cramariuc and Mihaela Baibarac
Materials 2024, 17(24), 6127; https://doi.org/10.3390/ma17246127 - 14 Dec 2024
Viewed by 777
Abstract
Nanocomposites based on Fe3O4 and carbonaceous nanoparticles (CNPs), including carbon nanotubes (CNTs) and graphene derivatives (graphene oxide (GO) and reduced graphene oxide (RGO)), such as Fe3O4@GO, Fe3O4@RGO, and Fe3O4 [...] Read more.
Nanocomposites based on Fe3O4 and carbonaceous nanoparticles (CNPs), including carbon nanotubes (CNTs) and graphene derivatives (graphene oxide (GO) and reduced graphene oxide (RGO)), such as Fe3O4@GO, Fe3O4@RGO, and Fe3O4@CNT, have demonstrated considerable potential in a number of health applications, including tissue regeneration and innovative cancer treatments such as hyperthermia (HT). This is due to their ability to transport drugs and generate localized heat under the influence of an alternating magnetic field on Fe3O4. Despite the promising potential of CNTs and graphene derivatives as drug delivery systems, their use in biological applications is hindered by challenges related to dispersion in physiological media and particle agglomeration. Hence, a solid foundation has been established for the integration of various synthesis techniques for these nanocomposites, with the wet co-precipitation method being the most prevalent. Moreover, the dimensions and morphology of the composite nanoparticles are directly correlated with the value of magnetic saturation, thus influencing the efficiency of the composite in drug delivery and other significant biomedical applications. The current demand for this type of material is related to the loading of a larger quantity of drugs within the hybrid structure of the carrier, with the objective of releasing this amount into the tumor cells. A second demand refers to the biocompatibility of the drug carrier and its capacity to permeate cell membranes, as well as the processes occurring within the drug carriers. The main objective of this paper is to review the synthesis methods used to prepare hybrids based on Fe3O4 and CNPs, such as GO, RGO, and CNTs, and to examinate their role in the formation of hybrid nanoparticles and the correlation between their morphology, the dimensions, and optical/magnetic properties. Full article
(This article belongs to the Special Issue Featured Reviews on Carbon Materials)
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<p>Method of precipitation used for the formation of composite based on Fe<sub>3</sub>O<sub>4</sub> and CNPs, either CNTs or GO. Diagram created with Chemix (2024). Retrieved from <a href="https://chemix.org" target="_blank">https://chemix.org</a> Accessed on 4 October 2024.</p>
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<p>Method of heterocoagulation used for the formation of composite based on Fe<sub>3</sub>O<sub>4</sub> and CNPs, either CNTs or GO.</p>
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<p>Low-magnification TEM images of (<b>a</b>) GO, (<b>b</b>) M-GO, (<b>c</b>) RGO, and (<b>d</b>) M-RGO [<a href="#B19-materials-17-06127" class="html-bibr">19</a>]. Figure reused with permission from [<a href="#B19-materials-17-06127" class="html-bibr">19</a>]. Copyright 2017 Elsevier.</p>
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<p>(<b>a</b>) XRD pattern, (<b>b</b>) Raman spectroscopy, (<b>c</b>) FTIR, and (<b>d</b>) XPS spectra of prepared materials [<a href="#B19-materials-17-06127" class="html-bibr">19</a>]. Figure reused with permission from [<a href="#B19-materials-17-06127" class="html-bibr">19</a>]. Copyright 2017 Elsevier.</p>
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<p>TEM microphotographs of fCNTs (<b>a</b>), H1 (<b>b</b>), and H4 (<b>c</b>) size distribution of Fe<sup>2+</sup> and Fe<sup>3+</sup> within hybrid materials (<b>d</b>); XRD patterns of H1 (i) and H4 (ii) (<b>e</b>); and the magnetic hysteresis loops of H1 (i) and H4 (ii) (<b>f</b>), where H1 represents 1:1 ratio of fCNTs: Fe<sub>3</sub>O<sub>4</sub>, while H4 is represented by 1:4 ratio of fCNTs: Fe<sub>3</sub>O<sub>4</sub> (figure reused with permission from [<a href="#B23-materials-17-06127" class="html-bibr">23</a>]). Copyright 2019 Elsevier.</p>
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<p>The optimization of the Fe<sub>3</sub>O<sub>4</sub> surface with graphene derivatives to obtain a biocompatible composite capable of being used in cellular environments for biomedical applications. Diagram created with Chemix (2024). Retrieved from <a href="https://chemix.org" target="_blank">https://chemix.org</a>. Accessed on 9 October 2024.</p>
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<p>Diagram of the drug deliveries in both in vitro (<b>a</b>) and in vivo experimental studies (<b>b</b>) implying composites of graphene derivatives, Fe<sub>3</sub>O<sub>4</sub> nanoparticles, and anthracycline c hemotherapeutic drugs. Diagram created with Chemix (2024). Retrieved from <a href="https://chemix.org" target="_blank">https://chemix.org</a>. Accessed on 10 October 2024.</p>
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<p>Composites of CNTs/graphene derivatives in conjunction with iron oxide nanoparticles to facilitate BTE through the stimulation of osteogenic cells.</p>
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32 pages, 18436 KiB  
Article
Experimental Evaluation of the Effect of Degradation on the Mechanical Behavior and Morphometric Characteristics of Functionally Graded Polymer Scaffolds
by Nataliya Elenskaya, Ilia Vindokurov, Evgeniy Sadyrin, Andrey Nikolaev and Mikhail Tashkinov
Polymers 2024, 16(24), 3474; https://doi.org/10.3390/polym16243474 - 12 Dec 2024
Viewed by 552
Abstract
Bone transplantation ranks second worldwide among tissue prosthesis surgeries. Currently, one of the most promising approaches is regenerative medicine, which involves tissue engineering based on polymer scaffolds with biodegradable properties. Once implanted, scaffolds interact directly with the surrounding tissues and in a fairly [...] Read more.
Bone transplantation ranks second worldwide among tissue prosthesis surgeries. Currently, one of the most promising approaches is regenerative medicine, which involves tissue engineering based on polymer scaffolds with biodegradable properties. Once implanted, scaffolds interact directly with the surrounding tissues and in a fairly aggressive environment, which causes biodegradation of the scaffold material. The aim of this work is to experimentally investigate the changes in the effective mechanical properties of polylactide scaffolds manufactured using additive technologies. The mechanism and the rate of the degradation process depend on the chosen material, contact area, microstructural features, and overall architecture of sample. To assess the influence of each of these factors, solid samples with different dimensions and layers orientation as well as prototypes of functionally graded scaffolds were studied. The research methodology includes the assessment of changes in the mechanical properties of the samples, as well as their structural characteristics. Changes in the mechanical properties were measured in compression tests. Microcomputed tomography (micro-CT) studies were conducted to evaluate changes in the microstructure of scaffold prototypes. Changes caused by surface erosion and their impact on degradation were assessed using morphometric analysis. Nonlinear changes in mechanical properties were observed for both solid samples and lattice graded scaffold prototypes depending on the duration of immersion in NaCl solution and exposure to different temperatures. At the temperature of 37 °C, the decrease in the elastic modulus of solid specimens was no more than 16%, while for the lattice scaffolds, it was only 4%. For expedited degradation during a higher temperature of 45 °C, these ratios were 47% and 16%, respectively. The decrease in compressive strength was no more than 32% for solid specimens and 17% for scaffolds. The results of this study may be useful for the development of optimal scaffolds considering the impact of the degradation process on their structural integrity. Full article
(This article belongs to the Special Issue Development and Application of Polymer Scaffolds, 2nd Volume)
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<p>Bulk degradation and surface erosion processes [<a href="#B18-polymers-16-03474" class="html-bibr">18</a>].</p>
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<p>Visualization of structures with morphology gradient: (<b>a</b>) DDM; (<b>b</b>) DP<sub>II</sub>M.</p>
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<p>Images of samples produced from PLA.</p>
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<p>Averaged stress–strain curves for continuous cylindrical specimens: (<b>a</b>) specimens C–1 under degradation regime D–1; (<b>b</b>) specimens C–1 under degradation regime D–2; (<b>c</b>) specimens C–2 under degradation regime D–1; (<b>d</b>) specimens C–2 samples under degradation regime D–2; (<b>e</b>) C–3 samples under degradation regime D–1; (<b>f</b>) C–3 samples under degradation regime D–2. The data with the confidence interval for all presented experimental curves are presented in <a href="#app2-polymers-16-03474" class="html-app">Appendix B</a>.</p>
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<p>Variation in the compressive elastic modulus of cylindrical specimens depending on the degradation mode: (<b>a</b>) specimens C–1; (<b>b</b>) specimens C–2; (<b>c</b>) specimens C–3.</p>
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<p>Variation in the compressive elastic modulus of cylindrical specimens depending on the degradation mode: (<b>a</b>) specimens C–1; (<b>b</b>) specimens C–2; (<b>c</b>) specimens C–3.</p>
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<p>The effective response of samples with different layer orientation under compressive loading.</p>
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<p>The effect of degradation modes on the mechanical behavior in compression for continuous prismatic specimens P–2.</p>
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<p>Averaged experimental stress–strain curves for lattice specimens: (<b>a</b>) DDM, D–1 degradation mode; (<b>b</b>) DDM, D–2 degradation mode; (<b>c</b>) DP<sub>II</sub>M, D–1 degradation mode; (<b>d</b>) DP<sub>II</sub>M D–2 degradation mode. The data with the confidence interval for all presented experimental curves are presented in <a href="#app2-polymers-16-03474" class="html-app">Appendix B</a>.</p>
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<p>The results of microtomography for the DDM sample without degradation: (<b>a</b>) three-dimensional representation; (<b>b</b>) cross-section in the XZ plane; (<b>c</b>) cross-section in the XY plane; (<b>d</b>) cross-section in the YZ plane. Defects are marked with red circles.</p>
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<p>The results of microtomography for the DP<sub>II</sub>M sample without degradation: (<b>a</b>) three-dimensional representation; (<b>b</b>) cross-section in the XZ plane; (<b>c</b>) cross-section in the XY plane; (<b>d</b>) cross-section in the YZ plane. Defects are marked with red circles.</p>
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<p>The results of micro-CT for the DP<sub>II</sub>M sample with degradation in mode D–1 on day 14: (<b>a</b>) three-dimensional representation; (<b>b</b>) cross-section in the XZ plane; (<b>c</b>) cross-section in the XY plane; (<b>d</b>) cross-section in the YZ plane. Defects are marked with red circles.</p>
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<p>Equivalent Mises stress distributions over the volume of the initial structure (DP<sub>II</sub>M–M) and voxel-based reconstruction of the real sample (DP<sub>II</sub>M–S).</p>
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<p>Distribution of equivalent stresses (by Mises) over the volume of the structure.</p>
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<p>Averaged experimental stress–strain curves for C–1 specimens for degradation regimes D–1 and D–2 at different stages: (<b>a</b>) 3 days; (<b>b</b>) 7 days; (<b>c</b>) 11 days; (<b>d</b>) 14 days.</p>
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<p>Averaged experimental stress–strain curves for C–2 specimens for degradation regimes D–1 and D–2 at different stages: (<b>a</b>) 3 days; (<b>b</b>) 7 days; (<b>c</b>) 11 days; (<b>d</b>) 14 days.</p>
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<p>Averaged experimental stress–strain curves for C–3 specimens for degradation regimes D–1 and D–2 at different stages: (<b>a</b>) 3 days; (<b>b</b>) 7 days; (<b>c</b>) 11 days; (<b>d</b>) 14 days.</p>
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<p>Averaged experimental stress–strain curves for DDM lattice structures for degradation regimes D–1 and D–2 at different stages: (<b>a</b>) 3 days; (<b>b</b>) 7 days; (<b>c</b>) 11 days; (<b>d</b>) 14 days.</p>
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<p>Averaged experimental stress–strain curves for DP<sub>II</sub>M lattice structures for degradation regimes D–1 and D–2 at different stages: (<b>a</b>) 3 days; (<b>b</b>) 7 days; (<b>c</b>) 11 days; (<b>d</b>) 14 days.</p>
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<p>The results of micro-CT for the DDM sample with degradation in mode D–1 on day 14: (<b>a</b>) three-dimensional representation; (<b>b</b>) cross-section in the XZ plane; (<b>c</b>) cross-section in the XY plane; (<b>d</b>) cross-section in the YZ plane.</p>
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<p>The results of micro-CT for the DDM sample with degradation in mode D–2 on day 14: (<b>a</b>) three-dimensional representation; (<b>b</b>) cross-section in the XZ plane; (<b>c</b>) cross-section in the XY plane; (<b>d</b>) cross-section in the YZ plane.</p>
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<p>The results of micro-CT for the DP<sub>II</sub>M sample with degradation in mode D–2 on day 14: (<b>a</b>) three-dimensional representation; (<b>b</b>) cross-section in the XZ plane; (<b>c</b>) cross-section in the XY plane; (<b>d</b>) cross-section in the YZ plane.</p>
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16 pages, 4724 KiB  
Article
Various Hydrogel Types as a Potential In Vitro Angiogenesis Model
by Chloé Radermacher, Annika Rohde, Vytautas Kucikas, Eva Miriam Buhl, Svenja Wein, Danny Jonigk, Willi Jahnen-Dechent and Sabine Neuss
Gels 2024, 10(12), 820; https://doi.org/10.3390/gels10120820 - 12 Dec 2024
Viewed by 328
Abstract
Angiogenesis, the formation of new blood vessels, is a fundamental process in both physiological repair mechanisms and pathological conditions, including cancer and chronic inflammation. Hydrogels are commonly used as in vitro models to mimic the extracellular matrix (ECM) and support endothelial cell behavior [...] Read more.
Angiogenesis, the formation of new blood vessels, is a fundamental process in both physiological repair mechanisms and pathological conditions, including cancer and chronic inflammation. Hydrogels are commonly used as in vitro models to mimic the extracellular matrix (ECM) and support endothelial cell behavior during angiogenesis. Mesenchymal stem cells further augment cell and tissue growth and are therefore widely used in regenerative medicine. Here we examined the combination of distinct hydrogel types—fibrin, collagen, and human platelet lysate (HPL)—on the formation of capillaries in a co-culture system containing human umbilical vein endothelial cells (HUVECs) and bone marrow-derived mesenchymal stem cells (BM-MSCs). The mechanical properties and structural changes of the hydrogels were characterized through scanning electron microscopy (SEM) and nanoindentation over 10 days. Fibrin and HPL gels sustained complex network formations, with HPL gels promoting even vascular tube formation of up to 10-fold capillary caliber. Collagen gels supported negligible angiogenesis. Our results suggest that HPL gels in combination with MSC-EC co-culture may be employed to obtain robust vascularization in tissue engineering. This study provides a comparative analysis of fibrin, collagen, and HPL hydrogels, focusing on their ability to support angiogenesis under identical conditions. Our findings demonstrate the superior performance of HPL gels in promoting robust vascular structures, highlighting their potential as a versatile tool for in vitro angiogenesis modeling. Full article
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<p>Characterization of MSCs and HUVECs using flow cytometry. (<b>A</b>) In the upper row: a typical flow cytometric analysis of one exemplary MSC donor for stem cell markers, which should stain positive (CD73+, CD90+, CD105+), as well as surface markers of hematopoietic stem cells and endothelial cells, which should stain negative (CD34−, CD45−). In the lower row: a typical flow cytometric analysis of the HUVEC donor for endothelial-specific markers (CD31+ and vWF+) and hematopoietic stem cells, which should be stained negative (CD45−). (<b>B</b>) Flow cytometric quantification of surface marker expression of the 3 donors of BM-MSCs. CD34− and CD45− were negative for all cell types. High levels of CD73+ (&gt;99.8), CD90+ (&gt;99.8%), and CD105+ (&gt;98.8%) expression were detectable in all stem cell types. (<b>C</b>) Flow cytometric quantification of surface marker expression of the three donors of each cell type. CD45− was negative and CD31+ and vWF+ achieved high levels of expression, at 89.1% and 98.25%, respectively. The percentage indicates the percentage of cells that express the respective marker. Abbreviations: BM-MSCs, bone marrow-derived mesenchymal stem cells; HUVECs, human umbilical vein endothelial cells; vWF, von Willebrand factor. Biological <span class="html-italic">n</span> = 3 for BM-MSCs and <span class="html-italic">n</span> = 1 for HUVECs.</p>
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<p>Two-dimensional angiogenesis experiments. (<b>A</b>) Representative immunofluorescence-staining pictures with no additive, suramin, or VEGF addition on days 1, 7, and 10. CD31+ is shown in red and cell nuclei in blue (DAPI). Images were taken at 100× magnification; scale bar: 200 μm. (<b>B</b>) Quantification of the fluorescent microscopy pictures showing the number of branches/segments/junctions, total branch/segment length, and total mesh area of the three conditions on days 7 and 10. Two-way ANOVA was applied (<span class="html-italic">p</span> * ≤ 0.01, <span class="html-italic">p</span> ** ≤ 0.005, <span class="html-italic">p</span> *** ≤ 0.001, <span class="html-italic">p</span> **** ≤ 0.0001) with a Tukey post hoc test.</p>
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<p>Characterization of the hydrogels. (<b>A</b>) SEM pictures of the three different hydrogels after 1 day and 10 days in culture. Magnification of 20,000× with a scale bar of 3 µm. (<b>B</b>) Determination of Young’s elastic modulus of the hydrogels using nanoindentation to investigate stiffness and stability over time. Two-way ANOVA was applied (<span class="html-italic">p</span> * ≤ 0.01).</p>
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<p>Angiogenesis in hydrogels—representative immunofluorescence pictures of collagen, fibrin, and HPL on days 1, 7, and 10. Experiments were repeated with three different MSC donors. CD31 is shown in red and cell nuclei in blue (DAPI). Images were taken at 100× magnification; scale bar: 200 μm.</p>
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<p>Angiogenesis in hydrogels—2-photon microscopy and TEM. (<b>A</b>) Immunofluorescence staining with no additive for each of the three gel types (fibrin, collagen, and HPL). For each gel type the diagonal, side, and top views are shown. (<b>B</b>) Diagonal and side views and stack image of HPL gel. The green circle highlights a formed lumen. CD31 is shown in red and DAPI in blue. The diagonal view, side view, and one stack image are shown for an immunofluorescence staining. (<b>C</b>) TEM visualization of lumens in HPL and fibrin gels with and without VEGF. The white dashed line indicates the lumen diameter for quantification.</p>
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20 pages, 7573 KiB  
Review
A Critical Review of Natural and Synthetic Polymer-Based Biological Apatite Composites for Bone Tissue Engineering
by Wasan Alkaron, Alaa Almansoori, Csaba Balázsi and Katalin Balázsi
J. Compos. Sci. 2024, 8(12), 523; https://doi.org/10.3390/jcs8120523 (registering DOI) - 12 Dec 2024
Viewed by 408
Abstract
During the past decade, there has been a continued increase in the demand for bone defect repair and replacement resulting from long-term illnesses or traumatic incidents. To address these challenges, tissue engineering research has focused on biomedical applications. This field concentrated on the [...] Read more.
During the past decade, there has been a continued increase in the demand for bone defect repair and replacement resulting from long-term illnesses or traumatic incidents. To address these challenges, tissue engineering research has focused on biomedical applications. This field concentrated on the development of suitable materials to enhance biological functionality and bone integration. Toward this aim, it is necessary to develop a proper material that provides good osseointegration and mechanical behavior by combining biopolymers with ceramics, which increase their mechanical stability and mineralization process. Hydroxyapatite (HAp) is synthesized from natural resources owing to its unique properties; for example, it can mimic the composition of bones and teeth of humans and animals. Biopolymers, including chitosan and alginate, combined with HAp, offer good chemical stability and strength required for tissue engineering. Composite biomaterials containing hydroxyapatite could be a potential substitute for artificial synthetic bone grafts. Utilizing various polymers and fabrication methodologies would efficiently customize physicochemical properties and suitable mechanical properties in synergy with biodegradation, thus enhancing their potential in bone regeneration. This review summarizes the commonly used polymers in tissue engineering, emphasizing their advantages and limitations. This paper also highlights recent advances in the production and investigation of HAp-based polymer composites used in biomedical applications. Full article
(This article belongs to the Special Issue Biopolymeric Matrices Reinforced with Natural Fibers and Nanofillers)
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<p>A classification of biodegradable polymers, with examples, based on their source.</p>
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<p>Schematic diagram of natural sources and synthesis methods for HAp.</p>
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<p>Schematic diagram of the solvent/casting solution process.</p>
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<p>SEM images of composite films immersed in simulated body fluid at a temperature of 36.5 °C for (<b>a</b>) 1, (<b>b</b>) 7, (<b>c</b>) 14, and (<b>d</b>) 21 days. Reproduced with permission [<a href="#B83-jcs-08-00523" class="html-bibr">83</a>].</p>
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<p>Schematic diagram of the freeze-drying process.</p>
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<p>Morphology of (<b>a</b>) a less dispersed film (−20 °C) and (<b>b</b>) a well dispersed film (−78 °C) [<a href="#B95-jcs-08-00523" class="html-bibr">95</a>].</p>
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<p>Schematic diagram of the electrospinning process.</p>
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<p>SEM of cell scaffolds cultured, at different magnifications (<b>a1</b>,<b>a2</b>), for 1 day, (<b>b1</b>,<b>b2</b>) 7 days, (<b>c1</b>,<b>c2</b>) and 14 days. Yellow marks show the anchorage sites of the cells. Reproduced with permission [<a href="#B108-jcs-08-00523" class="html-bibr">108</a>].</p>
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<p>SEM micrographs of scaffolds produced by electrospinning. (<b>a</b>) Chitosan/polyvinylalcohol (Chi/PVA) fibers, (<b>b</b>) Chi/PVA + 2% hydroxyapatite (HAp) (uncrosslinked), (<b>c</b>) Chi/PVA + 5% HAp (uncrosslinked), (<b>d</b>) Chi/PVA + 5% HAp (crosslinked) [<a href="#B109-jcs-08-00523" class="html-bibr">109</a>].</p>
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<p>(<b>a</b>) Photograph of n-HAp/PCL, (<b>b</b>) SEM micrographs of n-HAp/PCL, and (<b>c</b>) m-HAp/PCL [<a href="#B112-jcs-08-00523" class="html-bibr">112</a>].</p>
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<p>SEM microstructures of coatings deposited from methanolic (<b>a</b>–<b>c</b>), ethanolic (<b>d</b>–<b>f</b>), and isopropanolic (<b>g</b>–<b>i</b>) suspensions containing 0.5 g/L chitosan and 2 g/L (<b>a</b>,<b>d</b>,<b>g</b>), 5 g/L (<b>b</b>,<b>e</b>,<b>h</b>), and 10 g/L (<b>c</b>,<b>f</b>,<b>i</b>) HAp nanoparticles at 60 V/cm. Reproduced with permission [<a href="#B115-jcs-08-00523" class="html-bibr">115</a>].</p>
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11 pages, 3982 KiB  
Communication
Bioactive Agrocomposite for Tissue Engineering and Bone Regeneration
by Miguel Suffo, Celia Pérez-Muñoz, Daniel Goma-Jiménez, Carlos Revenga, Pablo Andrés-Cano and Miguel Ángel Cauqui-López
Inventions 2024, 9(6), 123; https://doi.org/10.3390/inventions9060123 - 9 Dec 2024
Viewed by 527
Abstract
Background: This study describes a novel biomaterial consisting of a mixture of biphasic bioceramic obtained from waste generated by the sugar industry (Carbocal) and a medical-grade epoxy resin adhesive called LOCTITE® M31 CLTM. The objective was to demonstrate the possibility of coating [...] Read more.
Background: This study describes a novel biomaterial consisting of a mixture of biphasic bioceramic obtained from waste generated by the sugar industry (Carbocal) and a medical-grade epoxy resin adhesive called LOCTITE® M31 CLTM. The objective was to demonstrate the possibility of coating non-bioactive and non-biodegradable metallic surfaces on implantable elements. Methods: After preparation, the mixture was applied to the surfaces of hip prostheses composed of two distinct materials: polyetherimide and grade 5 titanium. In both cases, adhesion tests produced favourable results. Additionally, cell cultures were conducted using human foetal osteoblastic cell lines (hFOB 1.19). Results: It was observed that the mixture did not affect the proliferation of bone cells. Conclusions: This composite material was found to promote the growth of bone cells, suggesting its potential for fostering bone tissue development. Full article
(This article belongs to the Section Inventions and Innovation in Biotechnology and Materials)
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<p>Sample preparation: (<b>a</b>) composite materials formed before coating the samples. Nomenclature I–VII corresponds to the compositions indicated in <a href="#inventions-09-00123-t002" class="html-table">Table 2</a>; (<b>b</b>) samples after coating 3 implantable surfaces (PEI-ULTEM1010<sup>®</sup> from the manufacturer Sabic (Riyadh, Saudi Arabia), Vitalium<sup>®</sup> from the manufacturer Dentsply Sirona (Charlotte, NC, USA), and Ti-6Al-4V); (<b>c</b>) implantable surfaces with adhesion test coatings: 1a—on femoral head on Vitalium material; 1b—different concentrations on small samples of Vitalium; 2a—epoxy only on flat surface of the intermediate part of the femoral stem of a hip prosthesis, manufactured in fused deposition (FDM) in material U1010; 2b—mixture VII on flat surface of the intermediate part of the femoral stem of a hip prosthesis, manufactured in FDM in material U1010; 2c—mixture VII on flat surface of the distal part of the femoral stem of a hip prosthesis, on loan from Stryker Iberia S.L. (Alcobendas, Madrid, Spain) in Ti-6Al-4V material.</p>
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<p>Instrument with V-shaped blades at 30° used for the grating in the adhesion test.</p>
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<p>Viability of human osteoblasts after 24 h, 48 h, 72 h, and 7 days of incubation with the different biomaterials tested. Culture medium in the absence of any biomaterial was used as a positive control, while 70% methanol was used as a negative control. X: sample tested; Y: viability (%).</p>
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<p>Growth of cells adhered to the surface of the biomaterial VI; (<b>a</b>) cells fixed with 70% methanol; (<b>b</b>) live cells.</p>
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<p>Growth of cells adhered to the surface of the biomaterial VII; (<b>a</b>) cells fixed with 70% methanol; (<b>b</b>) live cells.</p>
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<p>Viability of human osteoblasts after 24 h, 48 h, 72 h, and 7 days of incubation with samples VI and VII. Culture medium in the absence of any biomaterial was used as a positive control, while 70% methanol was used as a negative control. X: measure of time (hours/days); Y: viability (%).</p>
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<p>Results of adhesion tests of the biomaterial to implantable surfaces; (<b>a</b>) coating applied on the distal part of the Ti5 hip prosthesis; (<b>b</b>) coating applied to the femoral head of the hip prosthesis made of Vitalium; (<b>c</b>) coating applied on the intermediate area of the femoral stem of the hip prosthesis, manufactured in FDM 3D printing in U1010 material. In the enlarged view, two coatings can be seen, type I on the left and type VII on the right.</p>
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32 pages, 12061 KiB  
Article
Design of Trabecular Bone Mimicking Voronoi Lattice-Based Scaffolds and CFD Modelling of Non-Newtonian Power Law Blood Flow Behaviour
by Haja-Sherief N. Musthafa and Jason Walker
Computation 2024, 12(12), 241; https://doi.org/10.3390/computation12120241 - 5 Dec 2024
Viewed by 578
Abstract
Designing scaffolds similar to the structure of trabecular bone requires specialised algorithms. Existing scaffold designs for bone tissue engineering have repeated patterns that do not replicate the random stochastic porous structure of the internal architecture of bones. In this research, the Voronoi tessellation [...] Read more.
Designing scaffolds similar to the structure of trabecular bone requires specialised algorithms. Existing scaffold designs for bone tissue engineering have repeated patterns that do not replicate the random stochastic porous structure of the internal architecture of bones. In this research, the Voronoi tessellation method is applied to create random porous biomimetic structures. A volume mesh created from the shape of a Zygoma fracture acts as a boundary for the generation of random seed points by point spacing to create Voronoi cells and Voronoi diagrams. The Voronoi lattices were obtained by adding strut thickness to the Voronoi diagrams. Gradient Voronoi scaffolds of pore sizes (19.8 µm to 923 µm) similar to the structure of the trabecular bone were designed. A Finite Element Method-based computational fluid dynamics (CFD) simulation was performed on all designed Voronoi scaffolds to predict the pressure drops and permeability of non-Newtonian blood flow behaviour using the power law material model. The predicted permeability (0.33 × 10−9 m2 to 2.17 × 10−9 m2) values of the Voronoi scaffolds from the CFD simulation are comparable with the permeability of scaffolds and bone specimens from other research works. Full article
(This article belongs to the Section Computational Engineering)
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<p>Trabecular bone has interconnected random porous structures of divergent pore sizes and different thicknesses of struts (trabeculae). Modified and reproduced with permission from Ref. [<a href="#B13-computation-12-00241" class="html-bibr">13</a>] CC BY 3.0.</p>
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<p>Zygoma and volumes of interest: Jugale (Ju), Middle Point (M.P.) and Zygomaxillare (Zm). Reproduced with permission from Ref. [<a href="#B14-computation-12-00241" class="html-bibr">14</a>] CC BY 4.0. The Ju area has the highest bone volume density (23.2 ± 4.3%) and highest trabecular plate thickness (0.16 ± 0.05 mm) in edentulous maxillae, compared to those at M.P. and Zm areas [<a href="#B15-computation-12-00241" class="html-bibr">15</a>,<a href="#B16-computation-12-00241" class="html-bibr">16</a>].</p>
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<p>A Voronoi diagram and its tessellation patterns are based on random points to create the cells or regions in a given space. The boundary of each cell has an equal distance between two or more neighbouring points [<a href="#B40-computation-12-00241" class="html-bibr">40</a>].</p>
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<p>A Voronoi lattice-based cuboid biomimetic scaffold with functionally graded pores using a cloud of random seed points to create a stochastic microarchitecture.</p>
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<p>Zygoma model (front and back views) obtained from 3D scanning (EinScan-SE V2 3D scanner): Front view (<b>left</b>) and Back view (<b>right</b>) [<a href="#B14-computation-12-00241" class="html-bibr">14</a>].</p>
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<p>Virtual fracture process of zygoma: (<b>a</b>) fracture by a box, (<b>b</b>) fractured zygoma, and (<b>c</b>) extraction of the shape of the fracture for the design of Voronoi scaffolds (measurements in mm). (Refer: <a href="#app2-computation-12-00241" class="html-app">Appendix A</a> <a href="#computation-12-00241-f0A1" class="html-fig">Figure A1</a>).</p>
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<p>Random seed points inside the boundary layer with a distance known as point spacing. (Refer to <a href="#app3-computation-12-00241" class="html-app">Appendix B</a> <a href="#computation-12-00241-f0A2" class="html-fig">Figure A2</a>a).</p>
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<p>Conversion of scaffold shape (bone defect region) given on the left side into a volume mesh (Boundary layer) given on the right side. (Refer: <a href="#app3-computation-12-00241" class="html-app">Appendix B</a> <a href="#computation-12-00241-f0A2" class="html-fig">Figure A2</a>b).</p>
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<p>Creation of Voronoi lattices V90, V85, V80, V75 and V70 of porosities 90%, 85%, 80%, 75% and 70%, respectively. (Refer: <a href="#app3-computation-12-00241" class="html-app">Appendix B</a>).</p>
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<p>JT CAD files of different Voronoi scaffolds (front view) for CFD simulation.</p>
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<p>Surface wrapping method to create a fluid domain for the fluid surrounding the Voronoi V90 scaffold (solid domain).</p>
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<p>(<b>a</b>) Material properties of fluid and solid domains and (<b>b</b>) boundary conditions (velocity inlet, pressure outlet and no-slip wall condition) on the CFD model of the V90 scaffold.</p>
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<p>Generated volume mesh of the given (<b>a</b>) fluid domain and (<b>b</b>) solid domain of V90 scaffold for CFD simulation with tetrahedral elements and nodes.</p>
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<p>Scalar point maps and spheres are used to calculate pore sizes and pore numbers of all Voronoi lattice designs V90, V85, V80, V75, and V70. (Pore size calculation was carried out using the Lattice Pore size block of nTopology: Refer: <a href="#app3-computation-12-00241" class="html-app">Appendix B</a>).</p>
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<p>Graphs of variation of (<b>a</b>) surface area and (<b>b</b>) surface area/volume ratio (SA: V) with variation of porosities of Voronoi scaffolds.</p>
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<p>Testing of CFD models at different inlet velocities and the related pressure drops across the given Voronoi scaffolds.</p>
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<p>Velocity streamlines for all Voronoi scaffolds (V90, V85, V80, V75, V70) at inlet velocity 0.7 mm/s.</p>
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<p>Velocity streamlines for all Voronoi scaffolds (V90, V85, V80, V75, V70) at inlet velocity 0.7 mm/s.</p>
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<p>Pressure contours for all Voronoi scaffolds (V90, V85, V80, V75, V70) at inlet velocity of 0.7 mm/s.</p>
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<p>Variation of pressure drop and permeability based on the variation of porosity at an inlet velocity of 0.7 mm/s.</p>
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<p>Validation of a non-Newtonian model by a Newtonian model (comparison of pressure contours of both models for V90 scaffold) at inlet velocity of 0.7 mm/s.</p>
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<p>Shear strain rate contour of CFD model of V90 scaffold.</p>
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<p>(<b>a</b>) Creation of a virtual fracture of a scaffold using a box. (<b>b</b>) Fractured zygoma region. (<b>c</b>) Extracting the macrostructure or shape of the scaffold from bone defect or fractured region.</p>
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<p>(<b>a</b>) Creation of random seed points inside the implicit region. (<b>b</b>) Creation of boundary volume for Voronoi cells (Refer to <a href="#computation-12-00241-f0A3" class="html-fig">Figure A3</a>c). (<b>c</b>) Creation of Voronoi lattice in boundary volume adding strut thickness of 0.11 mm. (<b>d</b>) V70 Voronoi lattice.</p>
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<p>(<b>a</b>) Creation of pore diameters using scalar point maps. (<b>b</b>) Formation of spheres inside the Voronoi lattice, and (<b>c</b>) Voronoi cells inside the boundary volume.</p>
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<p>Calculation of porosity, volume fraction and SA: V.</p>
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24 pages, 3604 KiB  
Article
Enhancement of Chondrogenic Differentiation in Bone Marrow-Derived Stem Cell Spheroids by Cuminum cyminum Methanolic Extract: Insights into Concentration-Dependent mRNA Expression and Gene Clustering Analysis
by Kyung-Hwan Na, Hyun-Jin Lee, Ju-Hwan Kim, Md. Salah Uddin, Yoon-Hee Park, Young-Min Song, Chul-Sung Park and Jun-Beom Park
J. Pers. Med. 2024, 14(12), 1142; https://doi.org/10.3390/jpm14121142 - 5 Dec 2024
Viewed by 639
Abstract
Background/Objectives: Cuminum cyminum L. has been utilized as a medicinal plant for centuries. This research sought to examine the effects of cumin methanolic extract (CMT) on the chondrogenic differentiation of human bone marrow-derived mesenchymal stem cells. Methods: Spheroids were generated using [...] Read more.
Background/Objectives: Cuminum cyminum L. has been utilized as a medicinal plant for centuries. This research sought to examine the effects of cumin methanolic extract (CMT) on the chondrogenic differentiation of human bone marrow-derived mesenchymal stem cells. Methods: Spheroids were generated using human stem cells and cultured with CMT at concentrations between 0 and 1 µg/mL. Morphological assessments and cell viability tests were conducted on days 1 and 3. Chondrogenic differentiation expression was evaluated through quantitative polymerase chain reaction, Western blot, and RNA sequencing. SOX9, FAM20B, COL2A1, and COL1A1 mRNA expression levels were determined using real-time polymerase chain reaction. Protein expression was analyzed via Western blot. Results: Throughout this study, the spheroids maintained their integrity and shape. No significant variations in spheroid diameter were observed among the groups. CMT treatment enhanced the expression of SOX9 and FAM20B. Conclusions: The methanolic extract of Cuminum cyminum facilitated chondrogenic differentiation in human bone marrow-derived mesenchymal stem cells by modulating SOX9 and FAM20B expression. This indicates its potential application in cartilage tissue engineering. Full article
(This article belongs to the Section Regenerative Medicine and Therapeutics)
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<p>Evaluation of morphology and cellular viability of stem cell spheroids. (<b>A</b>) Assessment of cell morphology on days 1, 3, 7, and 14 for various concentrations of cumin methanolic extract, as seen under 100× original magnification. The scale bar in the image represents 200 μm. (<b>B</b>) Diameters of the cell spheroids on days 1, 3, 7, and 14 for different concentrations of the cumin methanolic extract. *: There was statistical difference when compared with the control on day 1. **: Statistical differences were noted when compared with the control on day 1. ***: There was statistical difference when compared with the control on day 3. ****: Statistical differences were noted when compared with the control on day 7. *****: There was statistical difference when compared with the control on day 14. (<b>C</b>) Cellular viability of the spheroids using the Cell Counting Kit-8 on days 1, 3, 7, and 14 for various concentrations of the extract. *: There was a significantly higher value for the 1 μg/mL group when compared with the control group on day 14.</p>
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<p>Evaluation of morphology and cellular viability of stem cell spheroids. (<b>A</b>) Assessment of cell morphology on days 1, 3, 7, and 14 for various concentrations of cumin methanolic extract, as seen under 100× original magnification. The scale bar in the image represents 200 μm. (<b>B</b>) Diameters of the cell spheroids on days 1, 3, 7, and 14 for different concentrations of the cumin methanolic extract. *: There was statistical difference when compared with the control on day 1. **: Statistical differences were noted when compared with the control on day 1. ***: There was statistical difference when compared with the control on day 3. ****: Statistical differences were noted when compared with the control on day 7. *****: There was statistical difference when compared with the control on day 14. (<b>C</b>) Cellular viability of the spheroids using the Cell Counting Kit-8 on days 1, 3, 7, and 14 for various concentrations of the extract. *: There was a significantly higher value for the 1 μg/mL group when compared with the control group on day 14.</p>
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<p>Quantification of gene expression was performed using real-time polymerase chain reaction on day 14 for various concentrations of cumin methanolic extracts. Significant differences compared to the control group are indicated (*). (<b>A</b>) The expression of SOX9 was quantified, showing a significant increase in mRNA levels at a concentration of 0.001 μg/mL. (<b>B</b>) The expression of FAM20B mRNA was quantified, revealing significant differences in comparison to the control group. (<b>C</b>) The expression of COL2A1 mRNA was quantified. (<b>D</b>) The expression of COL1A1 was quantified, showing significant differences in mRNA levels compared to the control group.</p>
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<p>Quantification of gene expression was performed using real-time polymerase chain reaction on day 14 for various concentrations of cumin methanolic extracts. Significant differences compared to the control group are indicated (*). (<b>A</b>) The expression of SOX9 was quantified, showing a significant increase in mRNA levels at a concentration of 0.001 μg/mL. (<b>B</b>) The expression of FAM20B mRNA was quantified, revealing significant differences in comparison to the control group. (<b>C</b>) The expression of COL2A1 mRNA was quantified. (<b>D</b>) The expression of COL1A1 was quantified, showing significant differences in mRNA levels compared to the control group.</p>
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<p>Western blot analysis. (<b>A</b>) Western blot analysis to evaluate the expression levels of SOX9, collagen II, collagen I, and β-catenin at different concentrations of cumin methanolic extracts. (<b>B</b>) Quantification of expression of SOX9 protein by Western blot analysis on day 14 for different concentrations of cumin methanolic extracts. Significant increases in SOX9 mRNA expression were observed at a concentration of 0.001 and 0.01 μg/mL when compared to the control group (*). (<b>C</b>) Quantification of expression of collagen I protein by Western blot analysis on day 14 for different concentrations of cumin methanolic extracts.</p>
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<p>Western blot analysis. (<b>A</b>) Western blot analysis to evaluate the expression levels of SOX9, collagen II, collagen I, and β-catenin at different concentrations of cumin methanolic extracts. (<b>B</b>) Quantification of expression of SOX9 protein by Western blot analysis on day 14 for different concentrations of cumin methanolic extracts. Significant increases in SOX9 mRNA expression were observed at a concentration of 0.001 and 0.01 μg/mL when compared to the control group (*). (<b>C</b>) Quantification of expression of collagen I protein by Western blot analysis on day 14 for different concentrations of cumin methanolic extracts.</p>
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<p>Differentially expressed mRNAs in four different groups. The mRNAs were clustered based on their expression levels, and only those with a fold change greater than 2.0 and a log2 normalized data greater than 3 were included in the analysis. (<b>A</b>) The clustering analysis of differentially expressed mRNAs in the 0.001 μg/mL group compared to the control group. (<b>B</b>) The analysis of differentially expressed mRNAs in the 0.01 μg/mL group compared to the control group. (<b>C</b>) The clustering analysis of differentially expressed mRNAs in the 0.1 μg/mL group vs. the control group. (<b>D</b>) The analysis of mRNAs with differential expression in the 1 μg/mL group compared to the control group.</p>
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<p>Differentially expressed mRNAs in four different groups. The mRNAs were clustered based on their expression levels, and only those with a fold change greater than 2.0 and a log2 normalized data greater than 3 were included in the analysis. (<b>A</b>) The clustering analysis of differentially expressed mRNAs in the 0.001 μg/mL group compared to the control group. (<b>B</b>) The analysis of differentially expressed mRNAs in the 0.01 μg/mL group compared to the control group. (<b>C</b>) The clustering analysis of differentially expressed mRNAs in the 0.1 μg/mL group vs. the control group. (<b>D</b>) The analysis of mRNAs with differential expression in the 1 μg/mL group compared to the control group.</p>
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<p>Differentially expressed mRNAs in four different groups. The mRNAs were clustered based on their expression levels, and only those with a fold change greater than 2.0 and a log2 normalized data greater than 3 were included in the analysis. (<b>A</b>) The clustering analysis of differentially expressed mRNAs in the 0.001 μg/mL group compared to the control group. (<b>B</b>) The analysis of differentially expressed mRNAs in the 0.01 μg/mL group compared to the control group. (<b>C</b>) The clustering analysis of differentially expressed mRNAs in the 0.1 μg/mL group vs. the control group. (<b>D</b>) The analysis of mRNAs with differential expression in the 1 μg/mL group compared to the control group.</p>
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<p>Differentially expressed mRNAs in four different groups. The mRNAs were clustered based on their expression levels, and only those with a fold change greater than 2.0 and a log2 normalized data greater than 3 were included in the analysis. (<b>A</b>) The clustering analysis of differentially expressed mRNAs in the 0.001 μg/mL group compared to the control group. (<b>B</b>) The analysis of differentially expressed mRNAs in the 0.01 μg/mL group compared to the control group. (<b>C</b>) The clustering analysis of differentially expressed mRNAs in the 0.1 μg/mL group vs. the control group. (<b>D</b>) The analysis of mRNAs with differential expression in the 1 μg/mL group compared to the control group.</p>
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<p>Clustering heatmap of differentially expressed mRNAs in response to cumin methanolic extract (CMT) treatment. The clustering heatmap shows the expression patterns of 76 differentially expressed mRNAs (fold change &gt; 2, <span class="html-italic">p</span>-value &lt; 0.05) in bone marrow-derived mesenchymal stem cells (BMSCs) treated with cumin methanolic extract (CMT) at various concentrations (0.001–1 µg/mL) compared to the control group. Upregulated genes are shown in red, downregulated genes in blue, and the intensity of the color represents the magnitude of fold change.</p>
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<p>The expression of genes related to chondrogenesis. The extracellular matrix (ECM)receptor interaction pathway map generated using the Kyoto Encyclopedia of Genes and Genomes database. Differentially expressed genes involved in this pathway are highlighted, demonstrating the impact of cumin methanolic extracts on ECM interactions during chondrogenesis.</p>
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12 pages, 2825 KiB  
Case Report
Application of Hybrid External Skeletal Fixation with Bone Tissue Engineering Techniques for Comminuted Fracture of the Proximal Radius in a Dog
by Minji Bae, Byung-Jae Kang and Junhyung Kim
Animals 2024, 14(23), 3480; https://doi.org/10.3390/ani14233480 - 2 Dec 2024
Viewed by 531
Abstract
A seven-month-old male Pomeranian presented with left forelimb lameness after a fall. Radiographic assessment confirmed proximal radial head and ulnar comminuted fracture. The initial surgical intervention involved the use of hybrid external skeletal fixation (ESF) to stabilize the radial head, concomitant with the [...] Read more.
A seven-month-old male Pomeranian presented with left forelimb lameness after a fall. Radiographic assessment confirmed proximal radial head and ulnar comminuted fracture. The initial surgical intervention involved the use of hybrid external skeletal fixation (ESF) to stabilize the radial head, concomitant with the application of a composite of bone morphogenetic protein type 2 (BMP-2)-loaded hydroxyapatite and gelatin microparticles at the fracture site. Although successful radial head healing was achieved, the ESF pinholes caused a defect in the proximal ulnar diaphysis. Subsequently, the ESF was removed, and a locking plate was applied in conjunction with the BMP-2-loaded collagen membrane to correct the radius defect. Clinical follow-up at 4.8 years postoperatively revealed a mildly decreased range of motion of the affected elbow joint, but no clinical symptoms such as lameness. Radiography revealed minimal degenerative changes and a radioulnar synostosis. Computed tomography revealed differences in the leg length and bone density. Gait analysis revealed that the left forelimb had a significant improvement in weight-bearing capacity based on weight distribution–peak vertical force metrics, compared with the right forelimb. Based on clinical outcomes, the combined application of hybrid ESF and bone tissue engineering techniques can be considered a feasible alternative treatment for radial head fractures. Full article
(This article belongs to the Special Issue Small Animal Orthopedic Surgery, Physical Therapy and Rehabilitation)
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<p>(<b>A</b>) Preoperative radiography image. (<b>B</b>) Preoperative computed tomography reconstruction image.</p>
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<p>Intraoperative images taken during the first surgery. (<b>A</b>) Gelatin microparticle (GMP) loaded with BMP-2; (<b>B</b>) simulation of the external skeletal fixation (ESF) device on a 3D-printed model; (<b>C</b>) insertion of the BMP-2 loaded HA and GMP mixture at the radius defect site.</p>
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<p>Intraoperative images of the second surgery. (<b>A</b>) The collagen membrane loaded with BMP-2; (<b>B</b>) a collagen membrane covering the radius defect area; (<b>C</b>) locking plate fixation of the radius.</p>
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<p>Results of histological analysis at three months after BMP-2 loaded HA and GMP mixture insertion. (<b>A</b>) H&amp;E staining, (<b>B</b>) Masson’s trichrome staining image showing a section of the bone fragment. I: implant (black dotted lines). NB: new bone. Arrow: osteoblast. Asterisks: osteoclast. Scale bar: 20 μm.</p>
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<p>Sequential radiographic images are shown at 0 days (<b>A</b>), 4 weeks (<b>B</b>), and 8 weeks (<b>C</b>) after fixation of the hybrid ESF with bone graft materials. (<b>D</b>) Due to ESF pin hole defects, plate fixation with bone graft materials was performed at 12 weeks (<b>E</b>). Radiography showing radioulnar synostosis (<b>F</b>) 4.8 years after the insertion of the plate.</p>
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<p>(<b>A</b>) Measurement of the Hounsfield unit (HU) values in 70–80% of the distal to proximal length of the affected radius and the same level of the right radius from CT images. Bone mineral density was estimated from HU measurement at the cranial (purple), caudal (pink), medial (green), and lateral (orange) cortices. The mean cross-sectional BMD was calculated. (<b>B</b>) A significant difference in the mean HU value between bilateral radii can be observed.</p>
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<p>Gait analysis of the pressure sensor walkway. (<b>A</b>,<b>B</b>) The symmetry index of the left forelimb decreased after fixation of the radius locking plate (2nd Surgery). (<b>C</b>,<b>D</b>) Weight distribution of the bilateral limbs revealed a tendency towards restoration of the left forelimb function. PVF: peak vertical force; VI: vertical impulse; RF: right forelimb; LF: left forelimb; * significant change from pre-operation; <sup>†</sup> significant change from 12 days after fixation of radius locking plate.</p>
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26 pages, 972 KiB  
Review
Mesenchymal Stromal Cells for Aging Cartilage Regeneration: A Review
by Kun-Chi Wu, Yu-Hsun Chang, Dah-Ching Ding and Shinn-Zong Lin
Int. J. Mol. Sci. 2024, 25(23), 12911; https://doi.org/10.3390/ijms252312911 - 30 Nov 2024
Viewed by 1259
Abstract
Cartilage degeneration is a key feature of aging and osteoarthritis, characterized by the progressive deterioration of joint function, pain, and limited mobility. Current treatments focus on symptom relief, not cartilage regeneration. Mesenchymal stromal cells (MSCs) offer a promising therapeutic option due to their [...] Read more.
Cartilage degeneration is a key feature of aging and osteoarthritis, characterized by the progressive deterioration of joint function, pain, and limited mobility. Current treatments focus on symptom relief, not cartilage regeneration. Mesenchymal stromal cells (MSCs) offer a promising therapeutic option due to their capability to differentiate into chondrocytes, modulate inflammation, and promote tissue regeneration. This review explores the potential of MSCs for cartilage regeneration, examining their biological properties, action mechanisms, and applications in preclinical and clinical settings. MSCs derived from bone marrow, adipose tissue, and other sources can self-renew and differentiate into multiple cell types. In aging cartilage, they aid in tissue regeneration by secreting growth factors and cytokines that enhance repair and modulate immune responses. Recent preclinical studies show that MSCs can restore cartilage integrity, reduce inflammation, and improve joint function, although clinical translation remains challenging due to limitations such as cell viability, scalability, and regulatory concerns. Advancements in MSC delivery, including scaffold-based approaches and engineered exosomes, may improve therapeutic effectiveness. Potential risks, such as tumorigenicity and immune rejection, are also discussed, emphasizing the need for optimized treatment protocols and large-scale clinical trials to develop effective, minimally invasive therapies for cartilage regeneration. Full article
(This article belongs to the Special Issue New Insights into Human Mesenchymal Stem Cells)
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<p>Sources, properties, and therapeutic potential of mesenchymal stromal cells (MSCs) for osteoarthritis treatment. MSCs can be derived from adipose tissue, umbilical cord, bone marrow, placenta, and dental pulp. MSCs from these sources exhibit essential characteristics, including self-renewal and multipotency, and respond to specific signaling molecules (e.g., BMP, FGF, TGF-β, IGF-1, SOX9) that aid in their proliferation and differentiation. MSCs also possess immunomodulatory and anti-inflammatory properties, making them suitable for therapeutic applications. Upon differentiation, MSCs can become chondrocytes, cells critical for cartilage formation and maintenance. Chondrocytes produce key ECM components, including type II collagen and aggrecan, which are essential for joint health. The paracrine and immunomodulatory effects of MSCs, along with their differentiation potential, are utilized in treating osteoarthritis to alleviate inflammation, support tissue repair, and restore cartilage function. This approach offers a promising approach for managing joint degenerative diseases.</p>
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<p>Optimal delivery methods for mesenchymal stromal cells (MSCs) in joint regeneration. The three main delivery methods are scaffold, extracellular vesicles, and hydrogels. Scaffolds are porous, supportive structures that enable MSCs to attach and proliferate, thereby maintaining cell viability and providing structural stability at the target site. Extracellular vesicles, which are cell-free particles derived from MSCs, contain signaling molecules (e.g., RNA, proteins) that facilitate tissue repair through intercellular communication, eliminating the need to introduce live cells. Hydrogels, gel-like materials that encapsulate MSCs, provide a hydrated environment that protects cells and enables their gradual release, supporting sustained therapeutic effects. These three delivery methods are directed toward the joint, representing their potential applications in regenerative treatments for conditions like osteoarthritis or cartilage damage. This figure highlights the adaptability of MSC-based therapies and the importance of selecting optimal delivery vehicles to enhance clinical outcomes.</p>
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