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Carbohydrate Polymers Sep 2024Segmental bone defects can arise from trauma, infection, metabolic bone disorders, or tumor removal. Hydrogels have gained attention in the field of bone regeneration...
Segmental bone defects can arise from trauma, infection, metabolic bone disorders, or tumor removal. Hydrogels have gained attention in the field of bone regeneration due to their unique hydrophilic properties and the ability to customize their physical and chemical characteristics to serve as scaffolds and carriers for growth factors. However, the limited mechanical strength of hydrogels and the rapid release of active substances have hindered their clinical utility and therapeutic effectiveness. With ongoing advancements in material science, the development of injectable and biofunctionalized hydrogels holds great promise for addressing the challenges associated with segmental bone defects. In this study, we incorporated lyophilized platelet-rich fibrin (LPRF), which contains a multitude of growth factors, into a genipin-crosslinked gelatin/hyaluronic acid (GLT/HA-0.5 % GP) hydrogel to create an injectable and biofunctionalized composite material. Our findings demonstrate that this biofunctionalized hydrogel possesses optimal attributes for bone tissue engineering. Furthermore, results obtained from rabbit model with segmental tibial bone defects, indicate that the treatment with this biofunctionalized hydrogel resulted in increased new bone formation, as confirmed by imaging and histological analysis. From a translational perspective, this biofunctionalized hydrogel provides innovative and bioinspired capabilities that have the potential to enhance bone repair and regeneration in future clinical applications.
Topics: Animals; Iridoids; Gelatin; Rabbits; Hydrogels; Hyaluronic Acid; Bone Regeneration; Freeze Drying; Platelet-Rich Fibrin; Tissue Engineering; Cross-Linking Reagents; Tissue Scaffolds; Tibia
PubMed: 38823938
DOI: 10.1016/j.carbpol.2024.122174 -
Carbohydrate Polymers Sep 2024In this study, new types of hybrid double-network (DN) hydrogels composed of polyvinyl alcohol (PVA), chitosan (CH), and sodium alginate (SA) are introduced, with the...
In this study, new types of hybrid double-network (DN) hydrogels composed of polyvinyl alcohol (PVA), chitosan (CH), and sodium alginate (SA) are introduced, with the hypothesis that this combination and incorporating multi-walled carbon nanotubes (MWCNTs) and graphene nanoplatelets (GNPs) will enhance osteogenetic differentiation and the structural and mechanical properties of scaffolds for bone tissue engineering applications. Initially, the impact of varying mass ratios of the PVA/CH/SA mixture on mechanical properties, swelling ratio, and degradability was examined. Based on this investigation, a mass ratio of 4:6:6 was determined to be optimal. At this ratio, the hydrogel demonstrated a Young's modulus of 47.5 ± 5 kPa, a swelling ratio of 680 ± 6 % after 3 h, and a degradation rate of 46.5 ± 5 % after 40 days. In the next phase, following the determination of the optimal mass ratio, CNTs and GNPs were incorporated into the 4:6:6 composite resulting in a significant enhancement in the electrical conductivity and stiffness of the scaffolds. The introduction of CNTs led to a notable increase of 36 % in the viability of MG63 osteoblast cells. Additionally, the inhibition zone test revealed that GNPs and CNTs increased the diameter of the inhibition zone by 49.6 % and 52.6 %, respectively.
Topics: Chitosan; Alginates; Polyvinyl Alcohol; Tissue Scaffolds; Humans; Bone Regeneration; Hydrogels; Tissue Engineering; Nanotubes, Carbon; Osteoblasts; Graphite; Biomimetic Materials; Cell Survival; Cell Line
PubMed: 38823905
DOI: 10.1016/j.carbpol.2024.122232 -
Molecular Biology Reports Jun 2024The development of cost-effective, simple, environment-friendly biographene is an area of interest. To accomplish environmentally safe, benign culturing that has...
Exploring the biocompatibility and healing activity of actinobacterial-enhanced reduced nano-graphene oxide in in vitro and in vivo model and induce bone regeneration through modulation of OPG/RANKL/RUNX2/ALP pathways.
BACKGROUND
The development of cost-effective, simple, environment-friendly biographene is an area of interest. To accomplish environmentally safe, benign culturing that has advantages over other methods to reduce the graphene oxide (GO), extracellular metabolites from actinobacteria associated with mushrooms were used for the first time.
METHODS
Bactericidal effect of GO against methicillin-resistant Staphylococcus aureus, antioxidant activity, and hydroxyapatite-like bone layer formation, gene expression analysis and appropriate biodegradation of the microbe-mediated synthesis of graphene was studied.
RESULTS
Isolated extracellular contents Streptomyces achromogenes sub sp rubradiris reduced nano-GO to graphene (rGO), which was further examined by spectrometry and suggested an efficient conversion and significant reduction in the intensity of all oxygen-containing moieties and shifted crystalline peaks. Electron microscopic results also suggested the reduction of GO layer. In addition, absence of significant toxicity in MG-63 cell line, intentional free radical scavenging prowess, liver and kidney histopathology, and Wistar rat bone regeneration through modulation of OPG/RANKL/RUNX2/ALP pathways show the feasibility of the prepared nano GO.
CONCLUSIONS
The study demonstrates the successful synthesis of biographene from actinobacterial extracellular metabolites, its potential biomedical applications, and its promising role in addressing health and environmental concerns.
Topics: Graphite; Animals; Bone Regeneration; Rats; RANK Ligand; Osteoprotegerin; Humans; Rats, Wistar; Biocompatible Materials; Core Binding Factor Alpha 1 Subunit; Actinobacteria; Anti-Bacterial Agents; Antioxidants; Signal Transduction
PubMed: 38822942
DOI: 10.1007/s11033-024-09600-8 -
Clinical Oral Investigations Jun 2024This study aimed to assess membrane use with a bone substitute graft for guided bone regeneration (GBR) in experimental dehiscence defects.
The effect of a barrier membrane on the incorporation of deproteinized bovine bone mineral (DBBM) in experimental defects at the time of early implant placement. A preclinical study.
OBJECTIVES
This study aimed to assess membrane use with a bone substitute graft for guided bone regeneration (GBR) in experimental dehiscence defects.
MATERIALS AND METHODS
Maxillary second incisors (I2) in 9 dogs were extracted. Six weeks later, implants were inserted and experimental dehiscence defects (5 × 3 mm) created on the buccal aspect. The defects and surrounding bone were grafted with deproteinized bovine bone mineral. One side (test) was covered with a resorbable collagen membrane whereas the contralateral side (control) was not. After 6 weeks, histomorphometrical analysis was performed to evaluate: (a) first bone-to-implant contact (fBIC), (b) buccal bone thickness at 1 mm increments from implant shoulder, (c) regenerated area (RA), (d) area and percentages of new bone (B), bone substitute (BS) and mineralized tissue (MT).
RESULTS
The histological appearance was similar between test and control sites. At central and lateral sections, there were no differences between groups for fBIC, buccal bone thickness, RA, BS, B, %B, MT and %MT. At central sections, membrane use favoured more %BS and %MT (p = 0.052). There was significantly more B, %B and MT at lateral compared to central sections.
CONCLUSIONS
Membrane use tended to retain more bone substitute, but had no effect on new bone ingrowth. Lateral sections showed significantly more bone ingrowth and mineralized tissue compared to central sections, confirming that new bone ingrowth takes place mainly from the lateral walls of the defect.
CLINICAL RELEVANCE
Preclinical research to clarify the dynamics of bone regeneration in GBR procedures is relevant in clinical practice.
Topics: Animals; Cattle; Dogs; Bone Substitutes; Membranes, Artificial; Bone Regeneration; Incisor; Guided Tissue Regeneration, Periodontal; Maxilla; Dental Implants; Collagen; Surgical Wound Dehiscence; Minerals
PubMed: 38822921
DOI: 10.1007/s00784-024-05748-6 -
Journal of Dental Research May 2024A ligature-induced periodontitis model was established in wild-type and CD146; Rosa mice to explore the function of pericytes in alveolar bone formation. We found that...
A ligature-induced periodontitis model was established in wild-type and CD146; Rosa mice to explore the function of pericytes in alveolar bone formation. We found that during periodontitis progression and periodontal wound healing, CD146/NG2 pericytes were enriched in the periodontal tissue areas, which could migrate to the alveolar bone surface and colocalize with ALP/OCN osteoblasts. Chemokine C-X-C motif receptor 4 (CXCR4) inhibition using AMD3100 blocked CD146-Cre pericyte migration and osteogenesis, as well as further exacerbated periodontitis-associated bone loss. Next, primary pericytes were sorted out by magnetic-activated cell sorting and demonstrated that C-X-C motif chemokine ligand 12 (CXCL12) promotes pericyte migration and osteogenesis via CXCL12-CXCR4-Rac1 signaling. Finally, the local administration of an adeno-associated virus for Rac1 overexpression in NG2 pericytes promotes osteoblast differentiation of pericytes and increases alveolar bone volume in periodontitis. Thus, our results provided the evidence that pericytes may migrate and osteogenesis via the CXCL12-CXCR4-Rac1 axis during the pathological process of periodontitis.
PubMed: 38822570
DOI: 10.1177/00220345241244687 -
Scientific Reports May 2024This study investigated whether K-Patlak derived from a shortened scan time for dynamic F-NaF PET/CT in chronic kidney disease (CKD) patients undergoing hemodialysis can...
This study investigated whether K-Patlak derived from a shortened scan time for dynamic F-NaF PET/CT in chronic kidney disease (CKD) patients undergoing hemodialysis can provide predictive accuracy comparable to that obtained from a longer scan. Twenty-seven patients on chronic hemodialysis, involving a total of 42 scans between December 2021 and August 2023 were recruited. Dynamic F-NaF PET/CT scans, lasting 60-90 min, were immediately acquired post-injection, covering the mid-twelfth thoracic vertebra to the pelvis region. K-Patlak analysis was performed on bone time-activity curves at 15, 30, 45, 60, and 90 min in the lumbar spine (L1-L4) and both anterior iliac crests. Spearman's rank correlation (r) and interclass correlation coefficient were used to assess the correlation and agreement of K-Patlak between shortened and standard scan times. Bone-specific alkaline phosphatase (BsAP) and tartrate-resistant acid phosphatase isoform 5b (TRAP5b) were tested for their correlation with individual K-Patlak. Strong correlations and good agreement were observed between K-Patlak values from shortened 30-min scans and longer 60-90-min scans in both lumbar spine (r = 0.858, p < 0.001) and anterior iliac crest regions (r = 0.850, p < 0.001). The correlation between BsAP and K-Patlak in the anterior iliac crests was weak and statistically insignificant. This finding suggests that a proposed shortened dynamic F-NaF PET/CT scan is effective in assessing bone metabolic flux in CKD patients undergoing hemodialysis, offering a non-invasive alternative approach for bone turnover prediction.
Topics: Humans; Positron Emission Tomography Computed Tomography; Male; Female; Renal Dialysis; Middle Aged; Renal Insufficiency, Chronic; Aged; Sodium Fluoride; Fluorine Radioisotopes; Bone Remodeling; Lumbar Vertebrae; Adult; Alkaline Phosphatase; Tartrate-Resistant Acid Phosphatase; Ilium
PubMed: 38822011
DOI: 10.1038/s41598-024-63476-z -
Frontiers in Immunology 2024As the world population ages, osteoporosis, the most common disease of bone metabolism, affects more than 200 million people worldwide. The etiology is an imbalance in... (Review)
Review
As the world population ages, osteoporosis, the most common disease of bone metabolism, affects more than 200 million people worldwide. The etiology is an imbalance in bone remodeling process resulting in more significant bone resorption than bone remodeling. With the advent of the osteoimmunology field, the immune system's role in skeletal pathologies is gradually being discovered. The cytokine interferon-gamma (IFN-γ), a member of the interferon family, is an important factor in the etiology and treatment of osteoporosis because it mediates bone remodeling. This review starts with bone remodeling process and includes the cellular and key signaling pathways of bone remodeling. The effects of IFN-γ on osteoblasts, osteoclasts, and bone mass are discussed separately, while the overall effects of IFN-γ on primary and secondary osteoporosis are summarized. The net effect of IFN-γ on bone appears to be highly dependent on the environment, dose, concentration, and stage of cellular differentiation. This review focuses on the mechanisms of bone remodeling and bone immunology, with a comprehensive discussion of the relationship between IFN-γ and osteoporosis. Finding the paradoxical balance of IFN-γ in bone immunology and exploring the potential of its clinical application provide new ideas for the clinical treatment of osteoporosis and drug development.
Topics: Humans; Bone Remodeling; Osteoporosis; Interferon-gamma; Animals; Osteoclasts; Osteoblasts; Signal Transduction; Bone and Bones
PubMed: 38817601
DOI: 10.3389/fimmu.2024.1396122 -
Cell Biochemistry and Function Jun 2024Evidence is accumulating that osteal macrophages, in addition to bone-resorbing osteoclasts and bone-forming osteoblasts, participate vitally in bone remodeling process....
Evidence is accumulating that osteal macrophages, in addition to bone-resorbing osteoclasts and bone-forming osteoblasts, participate vitally in bone remodeling process. Oncostatin M (OSM), an inflammatory cytokine belonging to interleukin-6 superfamily, is recognized as an essential factor secreted by osteal macrophages to orchestrate bone remodeling. Osteoprotegerin (OPG) produced by osteoblasts regulates osteoclastogenesis. We have reported that bone morphogenetic protein-4 (BMP-4) stimulates OPG synthesis in MC3T3-E1 osteoblast-like cells, and that SMAD1/5/8(9), p38 mitogen-activated protein kinase (MAPK), and p70 S6 kinase are involved in the OPG synthesis. The present study aims to investigate the effect of OSM on the synthesis of OPG stimulated by BMP-4 in osteoblasts. OSM suppressed the release and the mRNA expression of OPG upregulated by BMP-4 in MC3T3-E1 cells. Neither the BMP-4-induced phosphorylation of SMAD1/5/9 nor that of p38 MAPK was affected by OSM. On the other hand, the phosphorylation of p70 S6 kinase stimulated by BMP-4 was considerably suppressed by OSM. These results strongly suggest that OSM suppresses the BMP-4-stimulated OPG synthesis via inhibition of the p70 S6 kinase-mediated pathway in osteoblast-like cells.
Topics: Animals; Mice; Oncostatin M; Osteoblasts; Osteoprotegerin; Bone Morphogenetic Protein 4; Ribosomal Protein S6 Kinases, 70-kDa; p38 Mitogen-Activated Protein Kinases; Phosphorylation; Cell Line
PubMed: 38817105
DOI: 10.1002/cbf.4068 -
Scientific Reports May 2024Bone graft granules implanted in bone defects come into physical contact with the host bone and form interconnected porous structure. However, there exists an accidental...
Bone graft granules implanted in bone defects come into physical contact with the host bone and form interconnected porous structure. However, there exists an accidental displacement of granules to unintended locations and leakage of granules from bone defects. Although covering the defect with a barrier membrane prevents granule emanation, this procedure is troublesome. To resolve these problems, we fabricated bioresorbable mesh cages (BRMc) in this study. Bone graft granules composed of carbonate apatite alone (Gr) and bioresorbable mesh cages (BRMc/Gr) introduced the bone graft granules and were implanted into the bone defect in the rabbit femur. Micro-computed tomography and histological analysis were conducted at 4 and 12 weeks after implantation. Osteoprogenitors in the bloodstream from the host bone passed through the pores of BRMc, penetrated the porous structure of graft granules, and might interact with individual granules. Then bone remodeling could progress actively and new bone was formed. The new bone formation was similar to the host bone at 12 weeks and there were minimal signs of local tissue inflammation. BRMc/Gr could reduce the risk of unwanted new bone formation occurring due to loss of granules from the bone defects compared with Gr because BRMc enclosed granules and prevent granules leakage from bone defects and BRMc could not induce unfavorable effects to forme new bone. Additionally, BRMc/Gr could keep granules assembled in one place, avoid displacement of granules to unintended locations, and carry easily. These results demonstrated that BRMc/Gr was effective in bone regeneration and improved clinical handling.
Topics: Animals; Rabbits; Femur; Bone Transplantation; X-Ray Microtomography; Absorbable Implants; Bone Regeneration; Osteogenesis
PubMed: 38816454
DOI: 10.1038/s41598-024-63067-y -
Bone Research May 2024Degenerated endplate appears with cheese-like morphology and sensory innervation, contributing to low back pain and subsequently inducing intervertebral disc...
Degenerated endplate appears with cheese-like morphology and sensory innervation, contributing to low back pain and subsequently inducing intervertebral disc degeneration in the aged population. However, the origin and development mechanism of the cheese-like morphology remain unclear. Here in this study, we report lumbar instability induced cartilage endplate remodeling is responsible for this pathological change. Transcriptome sequencing of the endplate chondrocytes under abnormal stress revealed that the Hippo signaling was key for this process. Activation of Hippo signaling or knockout of the key gene Yap1 in the cartilage endplate severed the cheese-like morphological change and disc degeneration after lumbar spine instability (LSI) surgery, while blocking the Hippo signaling reversed this process. Meanwhile, transcriptome sequencing data also showed osteoclast differentiation related gene set expression was up regulated in the endplate chondrocytes under abnormal mechanical stress, which was activated after the Hippo signaling. Among the discovered osteoclast differentiation gene set, CCL3 was found to be largely released from the chondrocytes under abnormal stress, which functioned to recruit and promote osteoclasts formation for cartilage endplate remodeling. Over-expression of Yap1 inhibited CCL3 transcription by blocking its promoter, which then reversed the endplate from remodeling to the cheese-like morphology. Finally, LSI-induced cartilage endplate remodeling was successfully rescued by local injection of an AAV5 wrapped Yap1 over-expression plasmid at the site. These findings suggest that the Hippo signaling induced osteoclast gene set activation in the cartilage endplate is a potential new target for the management of instability induced low back pain and lumbar degeneration.
Topics: Intervertebral Disc Degeneration; Animals; Signal Transduction; Osteoclasts; Hippo Signaling Pathway; Lumbar Vertebrae; Chemokine CCL3; Mice; Cartilage; Protein Serine-Threonine Kinases; Joint Instability; Chondrocytes; YAP-Signaling Proteins; Male; Mice, Inbred C57BL
PubMed: 38816384
DOI: 10.1038/s41413-024-00331-x