Rat Bone Research Articles

Zoledronate interrupts pre-osteoclast-induced angiogenesis via SDF-1/CXCR4 pathway

IntroductionIn this study, we tested the hypothesis that pre-osteoclast signaling is key in triggering post-traumatic angiogenesis in alveolar bone via the SDF-1/CXCR4 pathway. Interruption of osteoclast differentiation through zoledronate (Zol) disrupts the crosstalk between pre-osteoclasts and endothelial cells, hindering the initial angiogenic reaction following dental trauma. This disruption could therefore play a role in the pathogenesis of medication-related osteonecrosis of the jaw (MRONJ). MethodsThe effect of zoledronate on the expression of SDF1 was tested in pre-osteoclasts (POC) in vitro. Then, we tested the effect of pre-osteoclast conditioned medium on HUVEC cell differentiation, migration, tube-formation, and CXCR4 expression and activity in-vitro. Lastly, we quantified the effect of zoledronate treatment on post-traumatic vascular perfusion of alveolar bone, using microCT-angiography and immunohistochemistry. ResultsSDF-1 mRNA expression decreased in Zol-treated POCs (p = 0.02). Flow-Cytometry analysis showed a decrease in CXCL-12+ (SDF-1α) expressing POCs with Zol treatment (p = 0.0058). On the other hand, CXCR4 mRNA expression was significantly inhibited in Zol-treated HUVECs (p = 0.0063). CXCR4 protein expression and activity showed a corresponding dose-dependent downregulation HUVEC surface treated with conditioned media from POC treated with Zol (p = 0.008 and 0.03, respectively). Similar inhibition was observed of HUVEC migration (p = 0.0012), and tube formation (p < 0.0001), effects that were reversed with SDF-1. Finally, there was a significant reduction of CD31+ HUVECs in Alveolar bone of Zol-treated rats (p = 0.0071), confirmed by significantly lower percentage of blood vessel volume (p = 0.026), and marginally lower vessel number (p = 0.062) in the alveolar bone. ConclusionPre-osteoclasts play a crucial role in the initial angiogenic response in alveolar bone following dental extraction. Disruption of this process may be a predisposing factor to osteonecrosis.

The effect of resveratrol on the viability of rat bone marrow mesenchymal stem cells

The effect of resveratrol on the viability of rat bone marrow mesenchymal stem cells

Alginate-HEMA Hydrogels as Promising Biomaterials for Bone Regeneration: InVitro and InVivo Studies.

In the present work, the osteogenic and angiogenic properties of, previously developed, semi-interpenetrated HEMA-EGDMA polymeric networks (sIPN) with and without alginate with application in bone tissue engineering (BTE) were studied. Invitro characterization studies were performed using rat bone marrow progenitor cells (BMPCs), EA.hy926 endothelial cells, and rat vascular smooth muscle cells (VSMCs). Based on the invitro results of both this work and previous ones, the hydrogels were selected to carry out invivo studies to find out their capacity as a biomaterial using a bone regeneration model. Our results indicate that the incorporation of alginate into the HEMA-EGDMA polymeric network promotes osteogenic and angiogenic capacity in cell cultures of BMPCs and both EA.hy926 and VSMCs, respectively, and also increases bone formation and vascular structures in invivo studies, demonstrating its potential use as a biomaterial in BTE.

Injectable calcium phosphate cement integrated with BMSCs-encapsulated microcapsules for bone tissue regeneration

Injectable calcium phosphate cement (CPC) offers significant benefits for the minimally invasive repair of irregular bone defects. However, the main limitations of CPC, including its deficiency in osteogenic properties and insufficient large porosity, require further investigation and resolution. In this study, alginate-chitosan-alginate (ACA) microcapsules were used to encapsulate and deliver rat bone mesenchymal stem cells (rBMSCs) into CPC paste, while a porous CPC scaffold was established to support cell growth. Our results demonstrated that the ACA cell microcapsules effectively protect the cells and facilitate their transport into the CPC paste, thereby enhancing cell viability post-implantation. Additionally, the ACA + CPC extracts were found to stimulate osteogenic differentiation of rBMSCs. Furthermore, results from a rat cranial parietal bone defect model showed that ACA microcapsules containing exogenous rBMSCs initially improved thein situosteogenic potential of CPC within bone defects, providing multiple sites for bone growth. Over time, the osteogenic potential of the exogenous cells diminishes, yet the pores created by the microcapsules persist in supporting ongoing bone formation by recruiting endogenous cells to the osteogenic sites. In conclusion, the utilization of ACA loaded stem cell microcapsules satisfactorily facilitate osteogenesis and degradation of CPC, making it a promising scaffold for bone defect transplantation.

Viscoelastic Hydrogel Modulates Phenotype of Macrophage-Derived Multinucleated Cells and Macrophage Differentiation in Foreign Body Reactions.

Biomaterial-induced macrophage-derived multinucleated cells (MNCs) are often observed at or near material implantation sites, yet their subtypes and roles in tissue repair and wound healing remain unclear. This study compares material-induced MNCs to cytokine-induced MNCs using both in vitro and in vivo models. 3D-embedded Raw264.7 cells and rat bone marrow-derived monocytes (BMDMs), with or without cytokines such as IL-4 and RANKL, were characterized for their MNC morphologies and subtypes via in situ immunocytochemistry and flow cytometry. Macrophage polarization and osteoclastic differentiation were assessed through NO production, arginase activity, and tartrate-resistant acid phosphatase levels. 3D matrix-induced MNCs expressed the same phenotypic heterogeneity as the IL-4 and RANK-treated ones. 3D matrix-induced MNCs displayed the same phenotypic heterogeneity as those treated with IL-4 and RANKL. A high viscoelastic matrix (1006.48 ± 92.29 Pa) induced larger populations of proinflammatory and osteoclast-like MNCs, whereas a low viscoelastic matrix (38.61 ± 7.56 Pa) supported active differentiation and gene expression across pro-, anti-inflammatory, and osteoclast-like macrophages. Matrix viscoelasticity also influenced the effects of IL-4 and RANKL on macrophage-derived MNC polarization. In an in vivo subcutaneous implantation model, medium to high viscoelastic matrices exhibited higher populations of CD86+ and RANK+ MNCs, while low viscoelastic matrices showed higher populations of CD206+ MNCs. These findings suggest that matrix viscoelasticity modulates macrophage differentiation and MNC phenotype, with low viscoelastic matrices potentially favoring anti-inflammatory MNCs and macrophage differentiation suitable for subcutaneous implantation.

Application of lactoferrin for the prevention and restoration of bone tissue in Wistar rats under conditions of hindlimb unloading

The influence of gravitational unloading (antiorthostatic suspension) and subsequent recovery on the mineral density and mechanical properties of the femoral and tibial bones of Wistar rats was studied with oral administration of a biotechnological analog of human lactoferrin (200 mg/kg) derived from the milk of producer goats. Bone mineral density was determined by dual-energy X-ray absorptiometry, and strength and stiffness were assessed through three-point bending tests. It was shown that gravitational unloading for 21 days led to a decrease in the mineral density of the tibial and femoral bones. The administration of lactoferrin did not significantly affect the mineral density or projected area of the studied bones. No statistically significant differences in mechanical stiffness were found between the experimental groups, but after readaptation, the ultimate strength was significantly higher in the groups that received lactoferrin. Thus, the obtained results may indicate the potential of lactoferrin preparations as prophylactic agents for maintaining bone strength. At the same time, maintaining bone mineral density under deficit-stimulating conditions requires consideration of alternative dosages and delivery methods of the drug.

A MnO2 nanosheets doping double crosslinked hydrogel for cartilage defect repair through alleviating inflammation and guiding chondrogenic differentiation

The inflammatory microenvironment and inferior chondrogenesis are major symptoms after cartilage defect. Although various modifications strategies associated with hydrogels exhibit remarkable capacity of pro-cartilage regeneration, the adverse effect by prolonging inflammation is still formidable to hamper potential biomedical applications of different hydrogel implants. Herein, inspired by the repair microenvironment of articular cartilage defects, an injectable, immunomodulatory, and chondrogenic L-MNS-CMDA hydrogel is prepared through grafting vinyl and catechol groups to chitosan macromolecules using amide reaction, then further loading MnO2 nanosheets (MNS). The double crosslinking of photopolymerization and catechol oxidative polymerization endows L-MNS-CMDA hydrogel with preferable mechanical property, affording a suitable mechanical support for cartilage defect repair. Additionally, the robust tissue adhesion capability stemming from catechol groups guarantees the long-term retention of the hydrogel in the defect site. Meanwhile, L-MNS-CMDA hydrogel decomposes exogenous and intracellular H2O2 into O2 and H2O, to effectively alleviate cellular oxidative stress caused by long-term hypoxia. Under the synergies of catechol groups and MNS, L-MNS-CMDA hydrogel not only inhibits macrophages polarizing into M1 phenotype, but encourages them turn into M2 phenotype, thereby, reconstructing an immunization friendly microenvironment to ultimately enhance cartilage regeneration. Predictably, the hydrogel markedly induces rat bone marrow mesenchymal stem cells differentiating into chondrocytes by expressing abundant glycosaminoglycan and type II collagen. A cartilage defect model of rat knee joint indicates that L-MNS-CMDA hydrogel visually regulate the early inflammatory response of post-implantation, and facilitate cartilage regeneration and recovery of joint function after 12 weeks of post-implantation. All in all, this multifunctional L-MNS-CMDA hydrogel exhibits superior immunomodulatory and chondrogenic properties, holding immense clinical potential in the treatment of cartilage defects.

3D Bioprinted Chondrogenic Gelatin Methacrylate-Poly(ethylene glycol) Diacrylate Composite Scaffolds for Intervertebral Disc Restoration

Abstract Degenerative spine pathologies, including intervertebral disc (IVD) degeneration, present a significant healthcare challenge due to their association with chronic pain and disability. This study explores an innovative approach to IVD regeneration utilizing 3D bioprinting technology, specifically visible light-based digital light processing (VL-DLP), to fabricate tissue scaffolds that closely mimic the native architecture of the IVD. Utilizing a hybrid bioink composed of gelatin methacrylate (GelMA) and poly(ethylene glycol) diacrylate (PEGDA) at a 10% concentration, we achieved enhanced printing fidelity and mechanical properties suitable for load-bearing applications such as the IVD. Preconditioning rat bone marrow-derived mesenchymal stem cell (rBMSC) spheroids with chondrogenic media before incorporating them into the GelMA-PEGDA scaffold further promoted the regenerative capabilities of this system. Our findings demonstrate that this bioprinted scaffold not only supports cell viability and integration but also contributes to the restoration of disc height in a rat caudal disc model without inducing adverse inflammatory responses. The study underscores the potential of combining advanced bioprinting techniques and cell preconditioning strategies to develop effective treatments for IVD degeneration and other musculoskeletal disorders, highlighting the need for further research into the dynamic interplay between cellular migration and the hydrogel matrix.

Genotoxicity and safety profile of Eleview®: A submucosal injectable composition for endoscopic mucosal resection and endoscopic submucosal dissection

Background and Objectives: Eleview® submucosal injectable composition with methylene blue (MB), is intended for use in gastrointestinal endoscopic procedures. Given the recognised in vitro mutagenicity of MB, Eleview® mutagenic and genotoxic potentials and its safety profile in acute and subacute toxicity settings were assessed. Methods: Acute and subacute systemic toxicity were tested in rats and dogs, respectively. Ames test and chromosome aberration test in Chinese Hamster V79 cells, were performed. The ratio of polychromatic to normochromatic erythrocytes was assessed in rat bone marrow at the rat MTD. Results: Eleview® oral or intraperitoneal at 20 mL/kg or 50 mL/kg did not induce any acute toxic effects in rats. In dogs, Eleview® (15 mL) did not cause any relevant in-life observations or any histopathological changes in any organs/tissues or injection sites. Ames test demonstrated no concentration-related and reproducible increases in revertant colony numbers. No significant increase of chromosomally aberrant cells was noted in Chinese Hamster cells. Lastly, Eleview® did not elicit significant increase in micronucleated polychromatic erythrocyte frequency. Conclusion: No death or abnormal findings in the acute and subacute studies were observed for Eleview® administration. Eleview® is not genotoxic, nor mutagenic, proving to be a safe medical device to use in clinical practice.

IL-4 promotes chondrogenesis of bone marrow mesenchymal stem cellsand blockade of IL-4Rα retards the endochondral ossification during rat embryonic bone development.

Interleukin-4 (IL-4)/IL-4 receptor alpha (IL-4Rα) signalling pathways play important roles in the complex process of bone formation and bone remodelling. However, whether IL-4/IL-4Rα participates in skeletogenesis during embryonic development is not completely understood. We used the anti-IL-4Rα monoclonal antibody (anti-IL-4Rα mAb) as a powerful investigational tool to evaluate the potential roles of IL-4/IL-4Rα in the chondrogenic differentiation of rat bone marrow mesenchymal stem cells (BMSCs) in vitro. Simultaneously, we explored the effect of IL-4/IL-4Rα on bone ossification during rat embryo-fetal development. In this study, we found that, compared to the control group, IL-4 can significantly promote the chondrogenic differentiation of BMSCs. Furthermore, following exposure to anti-IL-4Rα mAb in pregnant rats, unexpected phenomena were observed in fetal bone development, including non-ossification of the fetal sternum, an incomplete ossification centre in long bones and a reduced number of ossification points in digit (toe) bones. To further investigate the underlying mechanism of the phenotype, we studied the rat sternum as the target organ, starting from different time points of sternum development in the embryonic stage. The results indicated that the retardation mainly occurred in the middle and late stages of embryonic development. This retardation was characterized by the inhibition of the differentiation process of mesenchymal stem cells into chondrocytes, resulting in reduced angiogenesis near the ossification centre, failure of osteoblasts to invade the centre of the cartilage body with the blood vessels and delayed formation of the primary ossification centre (POC). Overall, our study demonstrated the significant function of IL-4/IL-4Rα in chondrogenic differentiation of BMSCs and bone ossification during embryo-fetal development.

Research on silk fibroin composite materials for wet environment applications

Silk fibroin material has good mechanical properties and excellent biocompatibility as a natural biomaterial with broad application prospects. However, by applying regenerated silk fibroin in biomaterials with high mechanical strength requirements, such as bone materials, there are problems, such as insufficient mechanical properties and a significant decline in mechanical properties in the wet state. In this report, a silk fibroin composite that maintains high strength in the wet state was prepared by adding nano-SiO2 as a nano-strengthening filler to the silk protein material and employing an epoxy-based silane coupling agent KH560 as an interfacial reinforcing agent. The results showed that the dry compressive strength of the composite material was substantially increased compared with that of the pure silk protein material; the wet compressive strength was significantly increased compared with that of the pure silk fibroin material, and the decrease of the mechanical properties in the wet state was low. The cytotoxicity test results of the composites showed that the materials were not cytotoxic. Rat bone marrow mesenchymal stem cells were cultured on the surface of the composites, and the results indicated that the composites could support the proliferation of bone marrow mesenchymal stem cells. The silk fibroin nanocomposites developed in this work can be applied as bone repair materials.

The role of AKR1B10 in osteogenic differentiation of mesenchymal stem cells and atrophic nonunion

Atrophic nonunion is a chronic disease without effective medications. Here, high-throughput mRNA sequencing was used to explore the novel targets in atrophic nonunion. AKR1B10, a member of aldo-keto reductase family 1, is upregulated in atrophic nonunion tissues. There are currently no studies to reveal the role of AKR1B10 in atrophic nonunion. We used rat bone marrow-derived mesenchymal stem cells (BMSCs) to explore the effect of AKR1B10 on the osteogenic differentiation and autophagy. In vivo, we implanted collagen sponges loaded with LV-shAKR1B10-transduced BMSCs into rat fractured femurs to explore the role of AKR1B10 in fracture healing. The results showed that AKR1B10 reduced the activity of ALP, suppressed the expression of COL1A1, RUNX2 and OCN, and inhibited calcification deposition in osteogenically differentiated BMSCs. AKR1B10 reduced the expression of LC3II, decreased the number of autophagosomes, and promoted the expression of p62. In addition, the promoting effect of AKR1B10 knockdown on osteogenic differentiation of BMSCs was attenuated by 3-MA treatment. Implantation of collagen sponges found that knockdown of AKR1B10 promoted bone fracture healing. In conclusion, AKR1B10 inhibited the osteogenic differentiation and autophagy, and delayed the bone fracture healing. These results provide a new perspective on revealing the role of AKR1B10 in nonunion and may also provide a new therapeutic target for the treatment of nonunion.

Biomimetic mineralization of collagen from fish scale to construct a functionally gradient lamellar bone-like structure for guided bone regeneration

Wide used guided bone regeneration (GBR) membrane materials, such as collagen, Teflon, and other synthesized polymers, present a great challenge in term of integrating the mechanical property and degradation rate when addressing critical bone defects. Therefore, inspired by the distinctive architecture of fish scales, this study utilized epigallocatechin gallate to modify decellularized fish scales following biomimetic mineralization to fabricate a GBR membrane that mimics the structure of lamellar bone. The structure, physical and chemical properties, and biological functions of the novel GBR membrane were evaluated. Results indicate that the decellularized fish scale with 5 remineralization cycles (5R-E-DCFS) exhibited a composite and structure similar to natural bone and had a special functionally gradient mineral contents character, demonstrating excellent mechanical properties, hydrophilicity, and degradation properties. In vitro, the 5R-E-DCFS membrane exhibited excellent cytocompatibility promoting Sprague-Dawley (SD) rat bone marrow mesenchymal stem cell proliferation and differentiation up-regulating the expression of osteogenic-related genes and proteins. Furthermore, in vivo, the 5R-E-DCFS membrane promoted the critical skull bone defects of SD rats repairment and regeneration. Therefore, this innovative biomimetic membrane holds substantial clinical potential as an ideal GBR membrane with mechanical properties for space-making and suitable degradation rate for bone regeneration to manage bone defects.

SEC31a-ATG9a Interaction Mediates the Recruitment of COPII Vesicles for Autophagosome Formation.

Autophagy plays an important role in determining stem-cell differentiation. During the osteogenic differentiation of mesenchymal stem cells (MSCs), autophagosome formation is upregulated but the reason is unknown. A long-standing quest in the autophagy field is to find the membrane origin of autophagosomes. In this study, cytoplasmic coat protein complex II (COPII) vesicles, endoplasmic reticulum-derived vesicles responsible for the transport of storage proteins to the Golgi, are demonstrated to be a critical source of osteoblastic autophagosomal membrane. A significant correlation between the number of COPII vesicle and the autophagy level is identified in the rat bone tissues. Disruption of COPII vesicles restrained osteogenesis and decreased the number and size of autophagosomes. SEC31a (an outer coat protein of COPII vesicle) is found to be vital to regulate COPII vesicle-dependent autophagosome formation via interacting with ATG9a of autophagosomal seed vesicles. The interference of Sec31a inhibited autophagosome formation and osteogenesis in vitro and in vivo. These results identified a novel mechanism of autophagosome formation in osteogenic differentiation of stem cells and identified SEC31a as a critical protein that mediates the interplay between COPII and ATG9a vesicles. These findings broaden the understanding of the regulatory mechanism in the osteogenic differentiation of MSCs.

Protective effect of carvacrol hydrogel on the alveolar bone in rats with periodontitis.

This study aimed to investigate the protective effect and mechanism of carvacrol hydrogel on the alveolar bone in rats with periodontitis. A thermosensitive hydrogel supported by carvacrol was prepared using poloxamer and hydroxypropyl methyl cellulose as matrix. SD rats were randomly divided into blank group, periodontitis group, blank hydrogel group, and low-, medium-, and high-dose hydrogel groups. The periodontitis symptoms and the CT structure of the alveolar bone were observed. The changes in liver, spleen, kidney, and periodontal tissues were observed. The related indexes of bone metabolism in serum were detected. The expression of osteoprotegerin (OPG) and nuclear transcription factor-κB (NF-κB) pathway proteins was determined by Western blot. The levels of inflammatory factors were assessed by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Carvacrol hydrogel had good slow release, biocompatibility, and cell adhesion. The periodontitis of rats in the carvacrol hydrogel group was significantly alleviated, the expression of OPG protein in gingival tissue was significantly increased (P<0.01), and the levels of receptor activator of NF-κB ligand (RANKL), receptor activator of NF-κB (RANK), NF-κB protein, and inflammatory factors were significantly decreased (P<0.01). Carvacrol hydrogel can regulate the OPG and NF-κB pathways, reduce alveolar bone absorption, and improve periodontal inflammation.

Ghrelin alleviated TiO2 NPs-induced inhibition of endochondral osteogenesis and promoted longitudinal growth of long bones in juvenile rats via Wnt/β-catenin signaling pathway

Titanium dioxide nanoparticles (TiO2 NPs) are widely used in children’s daily necessities and foods, and their health hazards to children have attracted particular attention. Childhood is a critical time for accelerated bone growth and development. Current studies revealed that TiO2 NPs exposure causes bone damage in juvenile rats; however, the underlying mechanism is unknown. Ghrelin is a polypeptide hormone that is considered to be a candidate factor for regulating bone growth and development. In this research, 3-week-old juvenile male rats were administered 0, 100 or 200 mg/kg TiO2 NPs and 50 μg/kg ghrelin for 4 weeks to explore the underlying mechanism of TiO2 NPs-induced bone damage, and the protective effect of ghrelin. Our results revealed that TiO2 NPs resulted in decreased synthesis of bone growth-related hormones, disturbed bone metabolism, and destruction of bone structure. Further mechanism studies showed that TiO2 NPs inhibited Wnt/β-catenin pathway, reduced collagen synthesis, inhibited chondrocyte proliferation and differentiation, promoted chondrocyte apoptosis, and inhibited endochondral osteogenesis, ultimately leading to long bone longitudinal growth retardation and osteoporosis. Ghrelin alleviated the negative effects of TiO2 NPs-induced bone growth in juvenile rats by upregulating the Wnt/β-catenin signaling pathway. This study provided a reference for the clinical treatment of growth retardation and idiopathic short stature in juvenile children caused by environmental pollutants.

Low frequency‑pulsed electromagnetic fields promote osteogenic differentiation of bone marrow‑derived mesenchymal stem cells by regulating connexin 43 expression.

The present study investigated the effect of connexin 43 (Cx43) on the regulation of osteogenic differentiation of rat bone marrow-derived mesenchymal stem cells (BMSCs) using low-frequency-pulsed electromagnetic fields (LPEMF). The BMSCs were isolated and cultured in vitro using adherent whole-bone marrow cultures. CCK-8 assay was used to detect the effects of LPEMF on the proliferation ability of BMSCs and alkaline phosphatase (ALP) activity and the levels of osteogenic marker genes were detected to evaluate the osteogenic ability change following LPEMF treatment. Lentiviral vector-mediated RNA interference was transfected into BMSCs to inhibit the expression of Cx43 and western blotting was used to detect Cx43 expression. The BMSCs showed the highest proliferation following LPEMF treatment at 80 Hz for 1 h. The results of ALP activity, osteogenic marker genes and Alizarin Red S staining showed that the osteogenic ability was notably increased following LPEMF treatment at 80 Hz for 1 h. Cx43 expression increased during the osteogenic differentiation of BMSCs following LPEMF treatment at 80 Hz. The enhanced osteogenic differentiation of the LPEMF-treated BMSCs were partially reversed when Cx43 expression was inhibited. LPEMF may promote the osteogenic differentiation of BMSCs by regulating Cx43 expression and enhancing osteogenic ability.

Incorporation of small extracellular vesicles in PEG/HA-Bio-Oss hydrogel composite scaffold for bone regeneration

Stem cell derived small extracellular vesicles (sEVs) have emerged as promising nanomaterials for the repair of bone defects. However, low retention of sEVs affects their therapeutic effects. Clinically used natural substitute inorganic bovine bone mineral (Bio-Oss) bone powder lacks high compactibility and efficient osteo-inductivity that limit its clinical application in repairing large bone defects. In this study, a poly ethylene glycol/hyaluronic acid (PEG/HA) hydrogel was used to stabilize Bio-Oss and incorporate rat bone marrow stem cell-derived sEVs (rBMSCs-sEVs) to engineer a PEG/HA-Bio-Oss (PEG/HA-Bio) composite scaffold. Encapsulation and sustained release of sEVs in hydrogel scaffold can enhance the retention of sEVs in targeted area, achieving long-lasting repair effect. Meanwhile, synergistic administration of sEVs and Bio-Oss in cranial defect can improve therapeutic effects. The PEG/HA-Bio composite scaffold showed good mechanical properties and biocompatibility, supporting the growth of rBMSCs. Furthermore, sEVs enhancedin vitrocell proliferation and osteogenic differentiation of rBMSCs. Implantation of sEVs/PEG/HA-Bio in rat cranial defect model promotedin vivobone regeneration, suggesting the great potential of sEVs/PEG/HA-Bio composite scaffold for bone repair and regeneration. Overall, this work provides a strategy of combining hydrogel composite scaffold systems and stem cell-derived sEVs for the application of tissue engineering repair.

Evaluation of serum biomarkers after intra-articular injection of rat bone marrow-derived mesenchymal stem cells in a rat model of knee osteoarthritis

Evaluation of serum biomarkers after intra-articular injection of rat bone marrow-derived mesenchymal stem cells in a rat model of knee osteoarthritis

Inhibitory impact of a mesoporous silica nanoparticle-based drug delivery system on Porphyromonas gingivalis-induced bone resorption

Controlling and reducing plaque formation plays a pivotal role in preventing and treating periodontal disease, often utilizing antibacterial drugs to enhance therapeutic outcomes. Mesoporous silica nanoparticles (MSN), an FDA-approved inorganic nanomaterial, possess robust physical and chemical properties, such as adjustable pore size and pore capacity, easy surface modification, and high biosafety. Numerous studies have exploited MSN to regulate drug release and facilitate targeted delivery. This study aimed to synthesize an MSN-tetracycline (MSN-TC) complex and investigate its inhibitory potential on Porphyromonas gingivalis (P. gingivalis)-induced bone resorption. The antibacterial efficacy of MSN-TC was evaluated through bacterial culture experiments. A P. gingivalis-induced bone resorption model was constructed by subcutaneously injecting P. gingivalis around the cranial bone of rats. Micro-computed tomography was employed to assess the inhibitory impact of MSN and MSN-TC on bone resorption. Furthermore, the influence of MSN and MSN-TC on osteoclast differentiation was examined in vitro. The MSN exhibited optimal pore size and particle dimensions for effective loading and gradual release of TC. MSN-TC demonstrated significant bacteriostatic activity against P. gingivalis. MSN-TC-treated rats showed significantly reduced cranial bone tissue destruction compared to MSN or TC-treated rats. Additionally, both MSN and MSN-TC exhibited inhibitory effects on the receptor activator of nuclear factor kappa-Β ligand-mediated osteoclast differentiation. The MSN-TC complex synthesized in this study demonstrated dual efficacy by exerting antibacterial effects on P. gingivalis and by resisting osteoclast differentiation, thereby mitigating bone resorption induced by P. gingivalis.Graphical