Differentiation Of Stem Cells Research Articles

Circ_0104873 promotes osteoarthritis progression via miR-875-5p/NOTCH3/Notch signaling pathway

Osteoarthritis (OA) is the most common joint disease with high prevalence and incidence. Increasing reports has indicated that circular RNAs (circRNAs) are implicated in OA progression. Nevertheless, the roles and functions of most circRNAs in OA remain to be elucidated. In this study, we emphatically discussed circ-IQGAP1 (circ_0104873) in OA. Firstly, we discovered that circ_0104873 was dramatically overexpressed during osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). Several functional assays demonstrated that circ_0104873 inhibition repressed BMSCs proliferation and osteogenic differentiation. Moreover, mechanism assays also revealed that circ_0104873 sponged microRNA-875-5p (miR-875-5p) to up-regulate notch receptor 3 (NOTCH3), thereby activating the Notch signaling pathway. Rescue assays disclosed that circ_0104873 contributed to the development of OA via targeting miR-875-5p/NOTCH3 axis. In conclusion, circ_0104873 promoted the progression of OA by miR-875-5p/NOTCH3/Notch signaling pathway, which might provide a promising target for OA treatment.

Increased neutrophil extracellular traps caused by diet-induced obesity delay fracture healing.

Obesity, recognized as a risk factor for nonunion, detrimentally impacts bone health, with significant physical and economic repercussions for affected individuals. Nevertheless, the precise pathomechanisms by which obesity impairs fracture healing remain insufficiently understood. Multiple studies have identified neutrophil granulocytes as key players in the systemic immune response, being the predominant immune cells in early fracture hematomas. This study identified a previously unreported critical period for neutrophil infiltration into the callus. Invivo experiments demonstrated that diet-induced obesity (DIO) mice showed earlier neutrophil infiltration, along with increased formation of neutrophil extracellular traps (NETs), compared to control mice during the endochondral phase of fracture repair. Furthermore, Padi4 knockout was found to reduce NET formation and mitigate the fracture healing delays caused by high-fat diets. Mechanistically, invitro analyses revealed that NETs, by activating NLRP3 inflammasomes, inhibited the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and concurrently promoted M1-like macrophage polarization. These findings establish a connection between NET formation during the endochondral phase and delayed fracture healing, suggesting that targeting NETs could serve as a promising therapeutic approach for addressing obesity-induced delays in fracture recovery.

Enhancing osteogenic differentiation in human umbilical cord mesenchymal stem cells: A review

Background: The article aims to review osteogenic differentiation enhancement in human Umbilical Cord Mesenchymal Stem Cells (hUCMSCs). Material and Methods: The literature review was carried out in PUBMED with the keywords: human Umbilical Cord Mesenchymal Stem Cells (hUCMSCs) and osteogenic differentiation. Conclusions: Many research investigated the impact of different substances on the osteogenic differentiation of hUCMSCs and the appliance by which these substances promote osteogenesis in hUCMSCs which are a potential source for bone regeneration.

Nutrient-sensing alteration leads to age-associated distortion of intestinal stem cell differentiating direction

Nutrient-sensing pathways undergo deregulation in aged animals, exerting a pivotal role in regulating the cell cycle and subsequent stem cell division. Nevertheless, their precise functions in governing pluripotent stem cell differentiation remain largely elusive. Here, we uncovered a significant alteration in the cellular constituents of the intestinal epithelium in aged humans and mice. Employing Drosophila midgut and mouse organoid culture models, we made an observation regarding the altered trajectory of differentiation in intestinal stem cells (ISC) during overnutrition or aging, which stems from the erroneous activation of the insulin receptor signaling pathway. Through genetic analyses, we ascertained that the nutrient-sensing pathway regulated the direction of ISC differentiation by modulating the maturation of endosomes and SOX21A transcription factor. This study elucidates a nutrient-sensing pathway-mediated mechanism underlying stem cell differentiation, offering insights into the etiology of stem cell dysfunction in aged animals, including humans.

Oxytocin, the Love Hormone, in Stem Cell Differentiation

Oxytocin (OXT) is a neurohypophysial nonapeptide that exerts its effects mainly through the oxytocin receptor (OXTR). Several studies have pointed out the role of OXT in the modulation of stem cell (SC) fate and properties. SCs are undifferentiated cells characterized by a remarkable ability to self-renew and differentiate into various cell types of the body. In this review, we focused on the role of OXT in SC differentiation. Specifically, we summarize and discuss the scientific research examining the effects of OXT on mesodermal SC-derived lineages, including cardiac, myogenic, adipogenic, osteogenic, and chondrogenic differentiation. The available studies related to the effects of OXT on SC differentiation provide little insights about the molecular mechanism mediated by the OXT–OXTR pathway. Further research is needed to fully elucidate these pathways to effectively modulate SC differentiation and develop potential therapeutic applications in regenerative medicine.

Stem Cells Treatment for Subarachnoid Hemorrhage.

Subarachnoid hemorrhage (SAH) refers to bleeding in the subarachnoid space, which is a serious neurologic emergency. However, the treatment effects of SAH are limited. In recent years, stem cell (SC) therapy has gradually become a very promising therapeutic method and advanced scientific research area for SAH. The SCs used for SAH treatment are mainly bone marrow mesenchymal stem cells (BMSCs), umbilical cord mesenchymal stem cells (hUC-MSCs), dental pulp stem cells (DPSCs), neural stem cells (NSCs)/neural progenitor cell (NPC), and endothelial progenitor cell (EPC). The mechanisms mainly included differentiation and migration of SCs for tissue repair; alleviating neuronal apoptosis; anti-inflammatory effects; and blood-brain barrier (BBB) protection. The dosage of SCs was generally 106 orders of magnitude. The administration methods included intravenous injection, nasal, occipital foramen magnum, and intraventricular administration. The administration time is generally 1 hour after SAH modeling, but it may be as late as 24 hours or 6 days. Existing studies have confirmed the neuroprotective effect of SCs in the treatment of SAH. SC has great potential application value in SAH treatment, a few case reports have provided support for this. However, the relevant research is still insufficient and there is still a lack of clinical research on the SC treatment for SAH to further evaluate the effectiveness and safety before it can go from experiment to clinical application.

Electrospinning Aligned SF/Magnetic Nanoparticles-Blend Nanofiber Scaffolds for Inducing Skeletal Myoblast Alignment and Differentiation.

In the realm of skeletal muscle tissue engineering, anisotropic materials that emulate natural tissues show substantial promise. Electrospun scaffolds, mimicking the fibrillar structure of the extracellular matrix, are commonly employed but often fall short in achieving optimal alignment and mechanical strength. Silk fibroin has emerged as a versatile material in tissue engineering, valued for its biocompatibility, mechanical robustness, and biodegradability. However, conventional electrospinning methods of SF result in randomly oriented fibers, limiting their efficacy. In this work, we developed a straightforward method to fabricate directional tissue scaffolds using silk fibroin. By integrating a magnetic field collecting device and incorporating Fe3O4 nanoparticles into the spinning solution, we successfully produced well-aligned silk nanofiber scaffolds. These aligned fibers not only improved scaffold orientation and mechanical properties but also exhibited magnetic responsiveness. The aligned SF scaffolds effectively guided the adhesion, proliferation, and differentiation of mesenchymal stem cells along the fiber direction. Cultured on these scaffolds, myoblast C2C12 cells demonstrated oriented growth, highlighting the potential of aligned SF fibers in advancing skeletal muscle engineering for biomedical applications.

7-Ketocholesterol Effects on Osteogenic Differentiation of Adipose Tissue-Derived Mesenchymal Stem Cells

Some oxysterols were shown to promote osteogenic differentiation of mesenchymal stem cells (MSCs). Little is known about the effects of 7-ketocholesterol (7-KC) in this process. We describe its impact on human adipose tissue-derived MSC (ATMSC) osteogenic differentiation. ATMSCs were incubated with 7-KC in osteogenic or adipogenic media. Osteogenic and adipogenic differentiation was evaluated by Alizarin red and Oil Red O staining, respectively. Osteogenic (ALPL, RUNX2, BGLAP) and adipogenic markers (PPARƔ, C/EBPα) were determined by RT-PCR. Differentiation signaling pathways (SHh, Smo, Gli-3, β-catenin) were determined by indirect immunofluorescence. ATMSCs treated with 7-KC in osteogenic media stained positively for Alizarin Red. 7-KC in adipogenic media decreased the number of adipocytes. 7-KC increased ALPL and RUNX2 but not BGLAP expressions. 7-KC decreased expression of PPARƔ and C/EBPα, did not change SHh, Smo, and Gli-3 expression, and increased the expression of β-catenin. In conclusion, 7-KC favors osteogenic differentiation of ATMSCs through the expression of early osteogenic genes (matrix maturation phase) by activating the Wnt/β-catenin signaling pathway, while inhibiting adipogenic differentiation. This knowledge can be potentially useful in regenerative medicine, in treatments for bone diseases.

Role of hsa-miR-543-KIF5C/CALM3 pathway in neuron differentiation of embryonic mesenchymal stem cells.

Human umbilical cord mesenchymal stem cells (hUC-MSCs) have the ability to differentiate into nerve cells, which offers promising options for treating neurodegenerative diseases. To explore the important regulatory molecules of hUC-MSCs differentiation into neurons. In this research, the neural differentiation of hUC-MSCs was induced by a low-serum DMSO/BHA/DMEM medium. The GEO database was used to retrieve the relevant datasets. The starBase and miEAA databases were used for bioinformatics analysis. RT-qPCR was used to detect the hsa-miR-543 level and the mRNA levels of NSE, NeuN, NF-M, KIF5C, and CALM3. The protein levels of KIF5C and CALM3 were checked by western blotting. The expression levels of NSE, NeuN, NF-M, KIF5C, and CALM3 were elevated, while hsa-miR-543 was under-expressed in neuro-induced hUC-MSCs. The increase in NSE, NeuN, and NF-M mRNA levels induced by DMSO/BHA/DMEM was partially reversed by the knockdown of KIF5C and CALM3 in hUC-MSCs. Moreover, the transfection of hsa-miR-543 mimic partially countered the DMSO/BHA/DMEM-induced elevation in NSE, NeuN, NF-M, KIF5C, and CALM3 mRNA levels. KIF5C and CALM3 facilitated the neuronal differentiation of hUC-MSCs, whereas hsa-miR-543 exerted an opposing effect by negatively regulating KIF5C and CALM3.

Controlled TPCA-1 delivery engineers a pro-tenogenic niche to initiate tendon regeneration by targeting IKKβ/NF-κB signaling

Tendon repair remains challenging due to its poor intrinsic healing capacity, and stem cell therapy has emerged as a promising strategy to promote tendon regeneration. Nevertheless, the inflammatory environment following acute tendon injuries disrupts stem cell differentiation, leading to unsatisfied outcomes. Our study recognized the critical role of NF-κB signaling in activating inflammation and suppressing tenogenic differentiation of stem cells after acute tendon injury via multiomics analysis. TPCA-1, a selective inhibitor of IKKβ/NF-κB signaling, efficiently restored the impaired tenogenesis of stem cells in the inflammatory environment. By developing a microsphere-incorporated hydrogel system for stem cell delivery and controlled release of TPCA-1, we successfully engineered a pro-tenogenic niche to initiate tenogenesis for tendon regeneration. Collectively, we recognize NF-κB signaling as a critical target to tailor a pro-tenogenic niche and propose the combined delivery of stem cells and TPCA-1 as a potential strategy for acute tendon injuries.

Micro-thin hydrogel coating integrated in 3D printing for spatiotemporal delivery of bioactive small molecules.

Three-dimensional (3D) printing incorporated with controlled delivery is an effective tool for complex tissue regeneration. Here, we explored a new strategy for spatiotemporal delivery of bioactive cues by establishing a precise-controlled micro-thin coating of hydrogel carriers on 3D-printed scaffolds. We optimized the printing parameters for three hydrogel carriers, fibrin cross-linked with genipin (FibGen), methacrylate hyaluronic acid (HAMA), and multidomain peptides (MDP), resulting in homogenous micro-coating on desired locations in 3D printed PCL microfibers at each layer. Using the optimized multi-head printing technique, we successfully established spatial-controlled micro-thin coating of hydrogel layers containing profibrogenic small molecules, Oxo-M and 4-PPBP, and a chondrogenic cue, Kartogenin (KGN). The delivered small molecules showed sustained releases up to 28 days and guided regional differentiation of mesenchymal stem cells (MSCs), thus leading to fibrous and cartilaginous tissue matrix formation at designated scaffold regions in vitro and in vivo. Our micro-coating of hydrogel carriers may serve as an efficient approach to achieve spatiotemporal delivery of various bioactive cues through 3D printed scaffolds for engineering complex tissues.&#xD.

Kaempferol promotes osteogenic differentiation in bone marrow mesenchymal stem cells by inhibiting CAV-1.

Our study focused on the effects and molecular mechanisms of kaempferol, a major active component of Eucommia ulmoides Oliver (EUO), on the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). Target molecules for EUO, osteoarthritis, and osteogenic differentiation were identified through network pharmacology analysis. BMSCs were isolated and treated with various concentrations of kaempferol. Optimal concentration was determined through MTT assays. Osteogenic differentiation was assessed using alkaline phosphatase (ALP) and Alizarin Red S staining, while osteogenic markers (Collagen I, RUNX2, and OPN) and CAV-1 expression were analyzed using RT-qPCR and Western blot. The effects of combined treatment with kaempferol and an overexpression vector for CAV-1 (oe-CAV-1) on osteogenic differentiation were also observed. Network pharmacology analysis identified kaempferol as the primary active component influencing CAV-1 targeted in subsequent experiments. It was found that 10 µM kaempferol was optimal for treating BMSCs. Post-treatment, significant increases in ALP activity and calcium deposition were observed, along with elevated expression of osteogenic markers, and decreased CAV-1. Overexpression of CAV-1 significantly reversed the promotive effects of kaempferol on BMSC osteogenic differentiation, effectively inhibiting the process. Collectively, kaempferol promotes osteogenic differentiation in BMSCs by inhibiting CAV-1 expression.

A Study of JUN’s Promoter Region and Its Regulators in Chickens

Background: The Jun proto-oncogene (JUN), also referred to as C-JUN, is an integral component of the JNK signaling pathway, which is crucial for the formation and differentiation of spermatogonial stem cells (SSCs). Investigations into the transcriptional regulation of chicken JUN can offer a molecular foundation for elucidating its mechanistic role in SSCs. Methods: In this study, we successfully cloned a 2000 bp upstream sequence of the JUN transcription start site and constructed a series of pGL3 recombinant vectors containing JUN promoters of varying lengths. Results: We verified the promoter activity of the 2000 bp upstream sequence by assessing the fluorescence intensity of DF-1 and identified the promoter activities of different regions via dual-luciferase assays. The transcription of JUN and its promoter region spanning −700 to 0 bp was modulated by an activator of the JNK signaling pathway. Bioinformatics analysis revealed that this −700 to 0 bp region was highly conserved among avian species and predicted the presence of binding sites for Wilms tumor 1 (WT1) and CCAAT/enhancer binding protein alpha (CEBPA). The JNK signaling pathway activator was found to upregulate the expression of these transcription factors in DF-1 cells. Through the deletion of binding sites and the overexpression of WT1 and CEBPA, we demonstrated that WT1 inhibited the transcription of JUN, while CEBPA promoted it. Conclusions: In conclusion, the −700 to 0 bp region is the key region of the JUN promoter, with WT1 inhibiting JUN transcription. The results of the study not only provide ideas for exploring the regulatory mechanism of JUN in chicken SSCs, but also lay an important foundation for the study of avian SSCs.

Maternal NO2 exposure and fetal growth restriction: Hypoxia transmission and lncRNAs-proinflammation-mediated abnormal hematopoiesis

Epidemiological studies show a strong correlation between air pollution and fetal growth restriction (FGR), but existing results are controversial due to inherent limitations, such as causality of specific pollutants, developmental origin, and maternal-fetal transmission. To address this controversy, we first conducted a retrospective analysis of 28,796 newborns and revealed that maternal nitrogen dioxide (NO2) exposure during the second trimester was positively associated with FGR, with an adjusted odds ratio of 1.075 (95% confidence interval: 1.020-1.133) per 10 μg/m3 NO2 increase for small for gestational age. Then, by establishing an animal model of prenatal NO2 exposure, we confirmed its adverse effects on embryonic growth and hematopoiesis in the yolk sac and fetal liver, primarily affecting the differentiation of hematopoietic stem and progenitor cells and erythroid maturation. By applying internal exposure analyses coupled with 15N isotope tracing, we found that maternal NO2 inhalation induced acquired methemoglobinemia through its byproducts and placental hypoxia in pregnant mice. Importantly, by combining transcriptional profiling, bioinformatics analysis, and RNA binding protein immunoprecipitation (RIP)/chromatin immunoprecipitation (CHIP), we clarified that placental-fetal hypoxia transmission activated hypoxia-inducible factors, disturbed hematopoiesis through the hypoxia-inducible factor 1β-long noncoding RNAs-CCAAT/enhancer binding protein alpha-proinflammatory signaling pathway, ultimately contributing to FGR progression. These findings provide insights for risk prevention and clinical intervention to promote child well-being in NO2-polluted areas.

Differentiation of human umbilical cord mesenchymal stem cells into functional intestinal epithelial cells via conditioned medium co-culture

BackgroundThe induction of stem cell differentiation to generate intestinal epithelial cells (IECs) with absorptive functions offers significant therapeutic potential for treating conditions such as Crohn’s disease, ulcerative colitis, radiation enteritis, and other refractory intestinal epithelial injuries. Human umbilical cord mesenchymal stem cells (hUC-MSCs) are capable of differentiating into functional IEC-like cells. ObjectiveThis study aimed to induce the differentiation of hUC-MSCs into IECs using a conditioned medium co-culture method. MethodA culture medium derived from human IECs was used as the inductive medium to facilitate the differentiation of hUC-MSCs into IECs. The cellular morphology was assessed using inverted microscopy, and the expression of IEC markers, including Villin, CK20, CK8, and CK18 proteins, was analyzed via immunofluorescence staining. Furthermore, the expression levels of IEC markers, such as KRT18, were quantified using real-time quantitative PCR analysis. The functionality of the differentiated IECs in terms of sucrase secretion was assessed through sucrase activity assays. ResultsBy the 14th day of induction, hUC-MSCs exhibited a morphology similar to IECs and exhibited the expression of IEC markers, including the KRT18 gene and Villin, CK20, CK8, and CK18 proteins. Sucrase activity assays further confirmed that the differentiated cells demonstrated significant sucrase activity. ConclusionThe conditioned medium co-culture method effectively induced the differentiation of hUC-MSCs into functional IECs.

Sorted stem/progenitor epithelial cells of pubertal bovine mammary gland present limited potential to reconstitute an organised mammary epithelium after transplantation.

The development and maintenance of mammary gland tissue depend on the proliferation and differentiation of mammary stem and progenitor cells. Here, we investigated populations of mammary epithelial cells that are potential candidates for bovine mammary gland development using xenotransplantation into mice cleared mammary fat pad. Transplanted mammary explants from 17-month-old Holstein heifers developed outgrowths exhibiting the archetypal morphology and molecular marker distributions of the bovine gland. Xenotransplantation of sorted mammary epithelial cells (CD49fpos) into bovinised fat pads using inactivated bovine fibroblasts resulted in outgrowth developments with 50% take rate, but these lacked the ductal or alveolar epithelial structures of the normal mammary gland. Similar results were obtained with xenografts of candidate bovine mammary epithelial stem cells (CD49fhighCD24pos) or epithelial cells of the basal lineage (CD49fhighCD24neg) which also developed as clumps of cells surrounded by stromal stretches within the mouse adipose tissue. In conclusion, sorted cells showed compromised regenerative potential for epithelial morphogenesis. Further work is therefore needed to identify mammary stem/progenitor cells with full regenerative capabilities for biogenesis of normal mammary gland structure, with milk-secreting function.

Platinum Nanozyme-Loaded Dissolving Microneedles Scavenge ROS and Promote Lineage Progression for Androgenetic Alopecia Treatment.

Androgenetic alopecia (AGA) is a prevalent issue affecting the physical and mental health of individuals but with fewer current treatments. Platinum nanozymes (PtNZs) are known for their excellent ability to reduce and modulate the high oxidative stress environment in AGA pathology. And microneedles are used to overcome the skin barrier due to the poor permeability of PtNZs. Herein, dissolving microneedles loaded with PtNZs (Pt-MNs) are designed and successfully induced hair regeneration in the AGA model. Pt-MNs possessed adequate mechanical strength to breach the skin barrier for effective PtNZs delivery. In vivo, PtNZs first reduced reactive oxygen species (ROS) to oxygen, which recovered the AGA pathological environment. And the oxygen then increased oxidative phosphorylation, promoting the differentiation of hair follicle stem cells to achieve hair regeneration. The group treated with Pt-MNs with a dosing frequency of once every three days achieved faster hair growth than the daily application of the positive drug minoxidil. Further safety experiments showed that the application of Pt-MNs locally opened temporary and recoverable skin channels, with no retention of Pt in major organs, indicating high safety. In conclusion, this study indicated the potential of Pt-MNs as an effective method for treating AGA.

Latrophilin-2 Deletion in Cardiomyocyte Disrupts Cell Junction, Leading to D-CMP.

Latrophilin-2 (Lphn2), an adhesive GPCR (G protein-coupled receptor), was found to be a specific marker of cardiac progenitors during the differentiation of pluripotent stem cells into cardiomyocytes or during embryonic heart development in our previous studies. Its role in adult heart physiology, however, remains unclear. The embryonic lethality resulting from Lphn2 deletion necessitates the establishment of cardiomyocyte-specific, tamoxifen-inducible Lphn2 knockout mice, which was achieved by crossing Lphn2flox/flox mice with mice having MerCreMer (tamoxifen-inducible Cre recombinase) under the α-myosin heavy chain promoter. Tamoxifen treatment for several days completely suppressed Lphn2 expression, specifically in the myocardium, and induced the dilated cardiomyopathy (D-CMP) phenotype with serious arrhythmia and sudden death in a short period of time. Transmission electron microscopy showed mitochondrial abnormalities, blurred Z-discs, and dehiscent myofibrils. The D-CMP phenotype, or heart failure, worsened during myocardial infarction. In a mechanistic study of D-CMP, Lphn2 knockout suppressed PGC-1α and mitochondrial dysfunction, leading to the accumulation of reactive oxygen species and the global suppression of junctional molecules, such as N-cadherin (adherens junction), DSC-2 (desmocollin-2; desmosome), and connexin-43 (gap junction), leading to the dehiscence of cardiac myofibers and serious arrhythmia. In an experimental therapeutic trial, activators of p38-MAPK, which is a downstream signaling molecule of Lphn2, remarkably rescued the D-CMP phenotype of Lphn2 knockout in the heart by restoring PGC-1α and mitochondrial function and recovering global junctional proteins. Lphn2 is a critical regulator of heart integrity by controlling mitochondrial functions and cell-to-cell junctions in cardiomyocytes. Its deficiency leads to D-CMP, which can be rescued by activators of the p38-MAPK pathway.

Multispectral Imaging of Collagen, NAD(P)H and Flavin Autofluorescence in Mesenchymal Stem Cells Undergoing Trilineage Differentiation.

Understanding the molecular mechanisms of differentiation is important for regenerative medicine and developmental biology. This study aims to characterise the role of the glycolysis/oxidative phosphorylation balance as a driver of mesenchymal stem cell (MSC) differentiation. Cells were maintained in normal conditions or stimulated towards the MSC trilineage cell types over 21 days. Multispectral imaging of cell autofluorescence was applied as a non-invasive methodology to continuously image cultures in situ. Spectral signals for collagen, NAD(P)H, and flavins were unmixed. MSCs cultured under chondrogenic conditions exhibited increased collagen levels relative to controls. Following osteogenic induction, MSCs showed increased collagen levels relative to controls during the earlier stages of culture; however, control cells increased their collagen levels as they became confluent. MSCs cultured under adipogenic conditions exhibited lower levels of collagen than controls. The redox ratio (RR; NAD(P)H/flavins) immediately decreased during chondrogenesis, with this early effect persisting throughout the culture compared to control cells, which appeared to increase their RR, similar to osteogenesis. Adipogenesis resulted in a small increase in RR on day 2 relative to control cells, followed by a persistent decrease. Chondrogenic and adipogenic differentiation favoured oxidative phosphorylation, whereas osteogenesis and MSC overgrowth resulted in a glycolytic metabolism. Following consideration of these findings, as well as the diverse reports in the literature, it is concluded that neither enhanced oxidative phosphorylation nor glycolysis are fundamental to the canonical modes of differentiation, and researchers should avoid interpreting shifts as indicating differentiation.

From ROS scavenging to boosted osseointegration: cerium-containing mesoporous bioactive glass nanoparticles functionalized implants in diabetes

Excessive production of reactive oxygen species (ROS) around titanium implants under diabetic conditions causes persistent inflammation, leading to poor osseointegration and even implant failure. Surface modification is an effective way to promote ROS clearance, alleviate inflammation, and stimulate bone formation. In this study, a multifunctional coating is fabricated by introducing cerium (Ce)-containing mesoporous bioactive glass nanoparticles (Ce-MBGNs) onto the titanium surface via an electrophoretic deposition method. The incorporation of Ce-MBGNs remarkably improves surface hydrophilicity by increasing the surface areas. The bioactive ions are appropriately released, thereby promoting mesenchymal stem cell proliferation and differentiation under diabetic conditions. The conversion between Ce(III) and Ce(IV) endows Ce-MBGNs coating with antioxidative nanoenzymes properties to scavenge diabetes-induced ROS, resulting in macrophage polarization towards the anti-inflammatory phenotype. The therapeutic effect of Ce-MBGNs-modified titanium implants is also verified in diabetic rats by inhibiting inflammatory responses and accelerating early osseointegration. Taken together, the findings reveal that the ROS-scavenging and immunomodulation activity of the Ce-MBGNs coating contributes to enhanced osseointegration, and provides a novel implant surface for diabetic patients.