Enhance Bone Repair Research Articles

Adipose-derived stem cell exosomal miR-21-5p enhances angiogenesis in endothelial progenitor cells to promote bone repair via the NOTCH1/DLL4/VEGFA signaling pathway

BackgroundAngiogenesis is essential for repairing critical-sized bone defects. Although adipose-derived stem cell (ADSC)-derived exosomes have been shown to enhance the angiogenesis of endothelial progenitor cells (EPCs), the underlying mechanisms remain unclear. This study aims to explore the effects and mechanisms of ADSC-derived exosomes in enhancing bone repair by promoting EPC angiogenesis.MethodsTransmission electron microscopy, nanoparticle tracking analysis, and Dil reagent kit were employed to identify ADSC-derived exosomes and their internalization by EPCs. Micro-CT analysis, H&E staining, and Masson staining were used to assess bone mineral density (BMD), bone volume fraction (BV/TV), trabecular thickness (Tb.Th), and trabecular number (Tb.N), as well as the pathological changes and fibrosis at defect sites. Cell viability, migration, invasion, and tube formation of EPCs were evaluated using CCK-8, wound healing, Transwell, and tube formation assays. Immunohistochemical staining, RT-PCR, and Western blotting were utilized to measure the gene and protein expression of markers such as CD31, VEGFA, OCN, RUNX2, NOTCH1, and DLL4. Gene sequencing and bioinformatics analyses were conducted to identify the most highly expressed miRNA in exosomes, while miRDB and dual-luciferase reporter assays were used to explore the interaction between miR-21-5p and NOTCH1.ResultsThe ADSC-derived exosomes, averaging 126 nm in diameter, were internalized by EPCs. In vivo, these exosomes promoted new bone formation, increased BMD, BV/TV, Tb.Th, and Tb.N, reduced pathological damage to cranial defect tissues, enhanced vascular and bone tissue regeneration, and upregulated OCN and RUNX2 expression. In vitro, ADSC-derived exosomes enhanced EPC viability, migration, invasion, and tube formation. Both in vivo and in vitro experiments demonstrated that ADSC-derived exosomes upregulated CD31 and VEGFA expression. miR-21-5p, the most highly expressed miRNA in ADSC-derived exosomes, was found to target NOTCH1. Overexpression of miR-21-5p in these exosomes facilitated EPC migration, tube formation, and VEGFA expression while downregulating NOTCH1 and DLL4 expression. Inhibition of miR-21-5p produced opposite effects on EPCs.ConclusionsThese findings indicate that miR-21-5p in ADSC-derived exosomes promotes angiogenesis in EPCs to accelerate bone repair by targeting the NOTCH1/DLL4/VEGFA signaling pathway, offering a potential therapeutic strategy for bone defect treatment.Graphical

Progranulin-dependent repair function of Regulatory T cells drive bone fracture healing.

Local immunoinflammatory events instruct skeletal stem cells (SSCs) to repair/regenerate bone after injury, but mechanisms are incompletely understood. We hypothesized that specialized Regulatory T (Treg) cells are necessary for bone repair and interact directly with SSCs through organ-specific messages. Both in human patients with bone fracture and mouse model of bone injury, we identified a bone injury-responding Treg subpopulation with bone-repair capacity marked by CCR8. Local production of CCL1 induced a massive migration of CCR8+ Treg cells from periphery to the injury site. Depending on secretion of progranulin (PGRN), a protein encoded by the granulin (Grn) gene, CCR8+ Treg cells supported the accumulation and osteogenic differentiation of SSCs, and thereby bone repair. Mechanistically, we revealed that CCL1 enhanced expression level of basic leucine zipper ATF-like transcription factor (BATF) in CCR8+ Treg cells, which bound to Grn promoter and increased Grn translational output and then PGRN secretion. Together, our work provides a new perspective in osteoimmunology and highlights possible ways of manipulating Treg cell signaling to enhance bone repair and regeneration.

Sonification of Deproteinized Bovine Bone Functionalized with Genistein Enhances Bone Repair in Peri-Implant Bone Defects in Ovariectomized Rats

Estrogen deficiency is one of several contributing factors to catabolic changes in bone surrounding dental implants, impairing bone repair in defects requiring bone regeneration. Functionalizing bone substitutes is an alternative approach among various strategies to address this challenge. In this study, the aim was to evaluate the effect of functionalizing deproteinized bovine bone (Bio-Oss®, BO) with genistein via sonication on peri-implant bone defects in ovariectomized rats. The animals were randomly distributed according to the treatment into the following four groups (n = 10): BO sonicated with genistein (BOS + GEN), BO sonicated alone (BOS), untreated BO (BO), and blood clot only (CLOT). After twenty-eight days, implant removal torque was determined, and the peri-implant bone parameters were calculated based on computed microtomography. Additionally, the gene expression of bone turnover markers was evaluated. As a main result, the functionalization with genistein increased implant removal torque and the peri-implant bone volume in the BOS + GEN group compared to both BOS and BO groups (both p < 0.05). These findings suggest that the sonification of deproteinized bovine bone functionalized with genistein improves bone repair in peri-implant bone defects in ovariectomized rats.

Enhancing bone repair efficiency through synergistic modification of recombinant human collagen onto PLLA membranes

Enhancing bone repair efficiency through synergistic modification of recombinant human collagen onto PLLA membranes

Periostin+ myeloid cells improved long bone regeneration in a mechanosensitive manner

Myeloid cells are pivotal in the inflammatory and remodeling phases of fracture repair. Here, we investigate the effect of periostin expressed by myeloid cells on bone regeneration in a monocortical tibial defect (MTD) model. In this study, we show that periostin is expressed by periosteal myeloid cells, primarily the M2 macrophages during bone regeneration. Knockout of periostin in myeloid cells reduces cortical bone thickness, disrupts trabecular bone connectivity, impairs repair impairment, and hinders M2 macrophage polarization. Mechanical stimulation is a regulator of periostin in macrophages. By activating transforming growth factor-β (TGF-β), it increases periostin expression in macrophages and induces M2 polarization. This mechanosensitive effect also reverses the delayed bone repair induced by periostin deficiency in myeloid cells by strengthening the angiogenesis-osteogenesis coupling. In addition, transplantation of mechanically conditioned macrophages into the periosteum over a bone defect results in substantially enhanced repair, confirming the critical role of macrophage-secreted periostin in bone repair. In summary, our findings suggest that mechanical stimulation regulates periostin expression and promotes M2 macrophage polarization, highlighting the potential of mechanically conditioned macrophages as a therapeutic strategy for enhancing bone repair.

Synthetic Bone Blocks Produced by Additive Manufacturing in the Repair of Critical Bone Defects.

This study evaluated the efficacy of synthetic bone blocks, composed of hydroxyapatite (HA) or β-tricalcium phosphate (B-TCP), which were produced by additive manufacturing and used for the repair of critical size bone defects (CSDs) in rat calvaria. Sixty rats were divided into five groups (n = 12): blood clot (CONTROL), 3D-printed HA (HA), 3D-printed β-TCP (B-TCP), 3D-printed HA + autologous micrograft (HA+RIG), and 3D-printed β-TCP + autologous micrograft (B-TCP+RIG). CSDs were surgically created in the parietal bone and treated with the respective biomaterials. The animals were euthanized at 30 and 60 days postsurgery for microcomputed tomography (micro-CT) histomorphometric, and immunohistochemical analysis to assess new bone formation. Micro-CT analysis showed that both biomaterials were incorporated into the animals' calvaria. The HA+RIG group, especially at 60 days, exhibited a significant increase in bone formation compared with the control. The use of 3D-printed bioceramics resulted in thinner trabeculae but a higher number of trabeculae compared with the control. Histomorphometric analysis showed bone islands in close contact with the B-TCP and HA blocks at 30 days. The HA blocks (HA and HA+RIG groups) showed statistically higher new bone formation values with further improvement when autologous micrografts were included. Immunohistochemical analysis showed the expression of bone repair proteins. At 30 days, the HA+RIG group had moderate Osteopontin (OPN) staining, indicating that the repair process had started, whereas other groups showed no staining. At 60 days, the HA+RIG group showed slight staining, similar to that of the control. Osteocalcin (OCN) staining, indicating osteoblastic activity, showed moderate expression in the HA and HA+RIG groups at 30 days, with slight expression in the B-TCP and B-TCP+RIG groups. The combination of HA blocks with autologous micrografts significantly enhanced bone repair, suggesting that the presence of progenitor cells and growth factors in the micrografts contributed to the improved outcomes. It was concluded that 3D-printed bone substitute blocks, associated with autologous micrografts, are highly effective in promoting bone repair in CSDs in rat calvaria.

Enhancing osteoblast differentiation and bone repair: The priming effect of photobiomodulation on adipose stromal cells

Cellular therapy using adipose tissue–derived mesenchymal stromal cells (at-MSCs) has garnered attention for the treatment of bone defects. Therefore, preconditioning strategies to enhance the osteogenic potential of at-MSCs could optimize cell therapy outcomes, and photobiomodulation (PBM) therapy has emerged as an effective, noninvasive, and low-cost alternative. This study explored the impacts of PBM on at-MSCs differentiation and the subsequent repair of bone defects treated with cell injection. Rat at-MSCs were cultured and irradiated (at-MSCsPBM) following the PBM protocol (660 nm; 20 mW; 0.714 W/cm2; 0.14 J; 5 J/cm2). Cellular differentiation was assessed based on the expression of gene and protein markers. Reactive oxygen species (ROS) were detected using fluorescence. At-MSCsPBM were injected into 5-mm calvarial lesions, and bone formation was analyzed using micro-CT and histological evaluations. At-MSCs were used as control. Data were analyzed using the ANOVA or t-test. At-MSCsPBM exhibited high levels of gene and protein runt-related transcription factor-2 (Runx2) and alkaline phosphatase (Alp) expression. PBM increased ALP activity and significantly reduced ROS levels. In addition, PBM increased the expression of Wnt pathway–associated genes. In vivo, there was an increase in the morphometric parameters, including bone volume, percentage of bone volume, bone surface area, and trabecular number, in at-MSCsPBM-treated defects compared with those in the control. These findings suggest that PBM enhances the osteogenic potential of at-MSCs, thereby supporting the advancement of improved cellular therapies for bone regeneration.

Decoding Cold Therapy Mechanisms of Enhanced Bone Repair through Sensory Receptors and Molecular Pathways.

Applying cold to a bone injury can aid healing, though its mechanisms are complex. This study investigates how cold therapy impacts bone repair to optimize healing. Cold was applied to a rodent bone model, with the physiological responses analyzed. Vasoconstriction was mediated by an increase in the transient receptor protein channels (TRPs), transient receptor potential ankyrin 1 (TRPA1; p = 0.012), and transient receptor potential melastatin 8 (TRPM8; p < 0.001), within cortical defects, enhancing the sensory response and blood flow regulation. Cold exposure also elevated hypoxia (p < 0.01) and vascular endothelial growth factor expression (VEGF; p < 0.001), promoting angiogenesis, vital for bone regeneration. The increased expression of osteogenic proteins peroxisome proliferator-activated receptor gamma coactivator (PGC-1α; p = 0.039) and RNA-binding motif protein 3 (RBM3; p < 0.008) suggests that the reparative processes have been stimulated. Enhanced osteoblast differentiation and the presence of alkaline phosphatase (ALP) at day 5 (three-fold, p = 0.021) and 10 (two-fold, p < 0.001) were observed, along with increased osteocalcin (OCN) at day 10 (two-fold, p = 0.019), indicating the presence of mature osteoblasts capable of mineralization. These findings highlight cold therapy's multifaceted effects on bone repair, offering insights for therapeutic strategies.

Analysis of the CPZ/Wnt4 osteogenic pathway for high-bonding-strength composite-coated magnesium scaffolds through transcriptomics

Magnesium (Mg)-based scaffolds are garnering increasing attention as bone repair materials owing to their biodegradability and mechanical resemblance to natural bone. Their effectiveness can be augmented by incorporating surface coatings to meet clinical needs. However, the limited bonding strength and unclear mechanisms of these coatings have impeded the clinical utility of scaffolds. To address these issues, this study introduces a composite coating of high-bonding-strength polydopamine-microarc oxidation (PDA-MHA) on Mg-based scaffolds. The results showed that the PDA-MHA coating achieved a bonding strength of 40.56 ± 1.426 MPa with the Mg scaffold surface, effectively enhancing hydrophilicity and controlling degradation rates. Furthermore, the scaffold facilitated bone regeneration by influencing osteogenic markers such as RUNX-2, OPN, OCN, and VEGF. Transcriptomic analyses further demonstrated that the PDA-MHA/Mg scaffold upregulated carboxypeptidase Z expression and activated the Wnt-4/β-catenin signaling pathway, thereby promoting bone regeneration. Overall, this study demonstrated that PDA can synergistically enhance bone repair with Mg scaffold, broadening the application scenarios of Mg and PDA in the field of biomaterials. Moreover, this study provides a theoretical underpinning for the application and clinical translation of Mg-based scaffolds in bone tissue engineering endeavors.

Multifunctional Bionic Periosteum with Ion Sustained-Release for Bone Regeneration.

In this study, a novel bionic periosteum (BP)-bioactive glass fiber membrane (BGFM) is designed. The introduction of magnesium ion (Mg2+) and zinc ion (Zn2+) change the phase separation during the electrospinning (ES) jet stretching process. The fiber's pore structure transitions from connected to closed pores, resulting in a decrease in the rapid release of metal ions while also improving degradation via reducing filling quality. Additionally, the introduction of magnesium (Mg) and zinc (Zn) lead to the formation of negative charged tetrahedral units (MgO4 2- and ZnO4 2-) in the glass network. These units effectively trap positive charged metal ions, further inhibiting ion release. In vitro experiments reveal that the deigned bionic periosteum regulates the polarization of macrophages toward M2 type, thereby establishing a conducive immune environment for osteogenic differentiation. Bioinformatics analysis indicate that BP enhanced bone repair via the JAK-STAT signaling pathway. The slow release of metal ions from the bionic periosteum can directly enhance osteogenic differentiation and vascularization, thereby accelerating bone regeneration. Finally, the bionic periosteum exhibits remarkable capabilities in angiogenesis and osteogenesis, demonstrating its potential for bone repair in a rat calvarial defect model.

Enhancing bone repair through improved angiogenesis and osteogenesis using mesoporous silica nanoparticle-loaded Konjac glucomannan-based interpenetrating network scaffolds

We have fabricated and characterized novel bioactive nanocomposite interpenetrating polymer network (IPN) scaffolds to treat bone defects by loading mesoporous silica nanoparticles (MSNs) into blends of Konjac glucomannan, polyvinyl alcohol, and polycaprolactone. By loading MSNs, we developed a porous nanocomposite scaffold with mechanical strengths comparable to cancellous bone. In vitro cell culture studies proved the cytocompatibility of the nanocomposite scaffolds. RT-PCR studies confirmed that these scaffolds significantly upregulated major osteogenic markers. The in vivo chick chorioallantoic membrane (CAM) assay confirmed the proangiogenic activity of the nanocomposite IPN scaffolds. In vivo studies were performed using Wistar rats to evaluate the scaffolds' compatibility, osteogenic activity, and proangiogenic properties. Liver and renal function tests confirmed that these scaffolds were nontoxic. X-ray and μ-CT results show that the bone defects treated with the nanocomposite scaffolds healed at a much faster rate compared to the untreated control and those treated with IPN scaffolds. H&E and Masson's trichrome staining showed angiogenesis near the newly formed bone and the presence of early-stage connective tissues, fibroblasts, and osteoblasts in the defect region at 8 weeks after surgery. Hence, these advantageous physicochemical and biological properties confirm that the nanocomposite IPN scaffolds are ideal for treating bone defects.

Enhancement of Bone Repair in Diabetic Rats with Metformin-Modified Silicified Collagen Scaffolds.

Regenerating bone defects in diabetic rats presents a significant challenge due to the detrimental effects of reactive oxygen species and impaired autophagy on bone healing. To address these issues, a metformin-modified biomimetic silicified collagen scaffold is developed utilizing the principles of biomimetic silicification. In vitro and in vivo experiments demonstrated that the scaffold enhanced bone tissue regeneration within the diabetic microenvironment through the release of dual bio-factors. Further analysis reveals a potential therapeutic mechanism whereby these dual bio-factors synergistically promoted osteogenesis in areas of diabetic bone defects by improving mitochondrial autophagy and maintaining redox balance. The present study provides critical insights into the advancement of tissue engineering strategies aimed at bone regeneration in diabetic patients. The study also sheds light on the underlying biological mechanisms.

A photothermal responsive system accelerating nitric oxide release to enhance bone repair by promoting osteogenesis and angiogenesis

Managing bone defects remains a formidable clinical hurdle, primarily attributed to the inadequate orchestration of vascular reconstruction and osteogenic differentiation in both spatial and temporal dimensions. This challenge persists due to the constrained availability of autogenous grafts and the limited regenerative capacity of allogeneic or synthetic bone substitutes, thus necessitating continual exploration and innovation in the realm of functional and bioactive bone graft materials. While synthetic scaffolds have emerged as promising carriers for bone grafts, their efficacy is curtailed by deficiencies in vascularization and osteoinductive potential. Nitric oxide (NO) plays a key role in revascularization and bone tissue regeneration, yet studies related to the use of NO for the treatment of bone defects remain scarce. Herein, we present a pioneering approach leveraging a photothermal-responsive system to augment NO release. This system comprises macromolecular mPEG-P nanoparticles encapsulating indocyanine green (ICG) (NO-NPs@ICG) and a mPEG-PA-PP injectable thermosensitive hydrogel carrier. By harnessing the synergistic photothermal effects of near-infrared radiation and ICG, the system achieves sustained NO release, thereby activating the soluble guanylate cyclase (SGC)-cyclic guanosine monophosphate (cGMP) signaling pathway both in vitro and in vivo. This orchestrated cascade culminates in the facilitation of angiogenesis and osteogenesis, thus expediting the reparative processes in bone defects. In a nutshell, the NO release-responsive system elucidated in this study presents a pioneering avenue for refining the bone tissue microenvironment and fostering enhanced bone regeneration.

Near-Infrared Responsive Properties of Bone Repair Scaffolds Facilitated by Specific Osteoinductive Photothermal Converters for Highly Efficient Bone Repair.

The effective repair of bone defects has long been a major challenge in clinical practice. Currently, research efforts mostly focus on achieving sufficiently good bone repair, with little attention paid to achieving both good and fast repair. However, achieving highly efficient (H-efficient) bone repair, which is both good and fast, can shorten the treatment cycle and facilitate rapid patient recovery. Therefore, the development of a H-efficient bone repair material is of significant importance. This study incorporated the previously developed osteoinductive photothermal agent (PTA) BPICT into printing paste to prepare a near-infrared (NIR)-responsive BPICT scaffold. Subsequently, the effects of photothermal therapy (PTT) on bone repair and drug release were assessed in vitro. To further validate the H-efficient bone repair properties of the BPICT scaffold, the scaffold was implanted into bone defects and its ability to promote bone repair in vivo was evaluated through radiology and histopathological analysis. The results indicated that compared to scaffolds containing only Icaritin (ICT), the BPICT scaffold can achieve PTT to promote bone repair through NIR irradiation, while also enabling the controlled release of ICT from the scaffold to enhance bone repair. Within the same observation period, the BPICT scaffold achieves more efficient bone repair than the ICT scaffold, significantly shortening the bone repair cycle while ensuring the effectiveness of bone repair. Therefore, the NIR-responsive scaffold based on PTT-mediated controlled release of bone growth factors represents a feasible solution for promoting H-efficient bone repair in the area of bone defects.

Flexible microneedles incorporating gold nanorods and tacrolimus for effective synergistic photothermal-chemotherapy of rheumatoid arthritis

Transdermal drug delivery systems for rheumatoid arthritis (RA) have garnered substantial attention due to their great potential to overcome limitations observed in conventional oral or injection strategies, including limited selectivity and adverse effects on extra-articular tissues. Microneedles (MNs) appear to be highly desirable carriers for transdermal drug delivery of RA. However, microneedles typically are unable to keep up with the flexibility of joints, which decreases the effectiveness of administration. In this study, we developed a flexible microneedles (FMNs) delivery system. And gelatin was employed for the fabrication of flexible backings for microneedles owing to its excellent ductility and biocompatibility. We achieved synergisticphotothermal-chemotherapy of RA by incorporating the chemical drug Tacrolimus (TAC) and the photothermal agent gold nanorods (AuNRs) into dissolving microneedles. Results showed a high mechanical strength of the proposed FMNs. In the animal model of adjuvant-induced arthritis (AA), it is indicated that the prepared FMNs inhibited the expression of related inflammatory cytokines such as IL-1ß and TNF-α while enhancing bone repair and other related factors. Thus, the combination therapy of FMNs-mediated hyperthermia and chemotherapy can serve as a novel and synergistic treatment option for RA.

OSTEOINDUCTIVE CAPACITY OF PLATELET-RICH FIBRIN VS BIODENTINE FOR MANDIBLE FRACTURE

Highlights Biodentine has undergone thorough research as a bone grafting substance due to its ability to promote bone regeneration and effectively treat root or tooth fractures. PRF and Biodentine can stimulate osteogenesis, affecting bone repair, particularly in mandibular fractures. Abstract Background: Mandibular fracture is one of the most common fractures. The most common treatment for mandibular fractures is fixation. Therefore, xenogeneic agents such as platelet-rich fibrin (PRF) and Biodentine accelerate the reparative process. Biodentine is an interesting active ingredient that can induce bone regeneration. PRF and Biodentine can promote bone healing, but no literature discusses the differences between PRF and Biodentine osteoinduction mechanisms in treating mandibular fractures. Objective: This article aimed to compare the effect of osteoinductive PRF with Biodentine for mandibular fractures. Material and Method: The research was conducted as a scoping review by performing a thorough search of the PubMed, Scopus, Science Direct, Elsevier, and Google Scholar databases. The study was obtained based on literature studies in the form of journals and textbooks in the last ten years (2013-2023). Result: The osteoinductive effect and mechanism of Biodentine in enhancing bone repair are likely correlated with releasing biologically active ions from calcium silicate cement and stimulating gene expression Runx-2. PRF has an osteoinductive role, causing the mechanism of releasing growth factors such as PDGF, VEGF, TGF-β, and IGF that promote the osteogenic process. Conclusion: There was no significant difference in the osteoinduction effect of PRF and Biodentine because these materials have different mechanisms of action for bone repair.

Epimedium-Curculigo herb pair enhances bone repair with infected bone defects and regulates osteoblasts through LncRNA MALAT1/miR-34a-5p/SMAD2 axis.

Infected bone defects (IBDs) are the common condition in the clinical practice of orthopaedics. Although surgery and anti-infective medicine are the firstly chosen treatments, in many cases, patients experience a prolonged bone union process after anti-infective treatment. Epimedium-Curculigo herb pair (ECP) has been proved to be effective for bone repair. However, the mechanisms of ECP in IBDs are insufficiency. In this study, Effect of ECP in IBDs was verified by micro-CT and histological examination. Qualitative and quantitative analysis of the main components in ECP containing medicated serum (ECP-CS) were performed. The network pharmacological approaches were then applied to predict potential pathways for ECP associated with bone repair. In addition, the mechanism of ECP regulating LncRNA MALAT1/miRNA-34a-5p/SMAD2 signalling axis was evaluated by molecular biology experiments. Invivo experiments indicated that ECP could significantly promote bone repair. The results of the chemical components analysis and the pathway identification revealed that TGF-β signalling pathway was related to ECP. The results of invitro experiments indicated that ECP-CS could reverse the damage caused by LPS through inhibiting the expressions of LncRNA MALAT1 and SMAD2, and improving the expressions of miR-34a-5p, ALP, RUNX2 and Collagen type І in osteoblasts significantly. This research showed that ECP could regulate the TGF-β/SMADs signalling pathway to promote bone repair. Meanwhile, ECP could alleviate LPS-induced bone loss by modulating the signalling axis of LncRNA MALAT1/miRNA-34a-5p/ SMAD2 in IBDs.

The Uniform Distribution of Hydroxyapatite in a Polyurethane Foam-Based Scaffold (PU/HAp) to Enhance Bone Repair in a Calvarial Defect Model

Polyurethane (PU) is a promising material for addressing challenges in bone grafting. This study was designed to enhance the bone grafting capabilities of PU by integrating hydroxyapatite (HAp), which is known for its osteoconductive and osteoinductive potential. Moreover, a uniform distribution of HAp in the porous structure of PU increased the effectiveness of bone grafts. PEG/APTES-modified scaffolds were prepared through self-foaming reactions. A uniform pore structure was generated during the spontaneous foaming reaction, and HAp was uniformly distributed in the PU structure (PU15HAp and PU30HAp) during foaming. Compared with the PU scaffolds, the HAp-modified PU scaffolds exhibited significantly greater protein absorption. Importantly, the effect of the HAp-modified PU scaffold on bone repair was tested in a rat calvarial defect model. The microstructure of the newly formed bone was analyzed with microcomputed tomography (μ-CT). Bone regeneration at the defect site was significantly greater in the HAp-modified PU scaffold group than in the PU group. This innovative HAp-modified PU scaffold improves current bone graft materials, providing a promising avenue for improved bone regeneration.

Molecular mechanisms of EGCG-CSH/n-HA/CMC in promoting osteogenic differentiation and macrophage polarization

2.This research investigates the impact of the EGCG-CSH/n-HA/CMC composite material on bone defect repair, emphasizing its influence on macrophage polarization and osteogenic differentiation of BMSCs. Comprehensive evaluations of the composite’s physical and chemical characteristics were performed. BMSC response to the material was tested in vitro for proliferation, migration, and osteogenic potential. An SD rat model was employed for in vivo assessments of bone repair efficacy. Both transcriptional and proteomic analyses were utilized to delineate the mechanisms influencing macrophage behavior and stem cell differentiation. The material maintained excellent structural integrity and significantly promoted BMSC functions critical to bone healing. In vivo results confirmed accelerated bone repair, and molecular analysis highlighted the role of macrophage M2 polarization, particularly through changes in the SIRPA gene and protein expression. EGCG-CSH/n-HA/CMC plays a significant role in enhancing bone repair, with implications for macrophage and BMSC function. Our findings suggest that targeting SIRPA may offer new therapeutic opportunities for bone regeneration.

Efficacy of mesenchymal stem cell-based therapy on the bone repair of hypertensive rats.

Hypertension disrupts the bone integrity and its repair ability. This study explores the efficiency of a therapy based on the application of mesenchymal stem cells (MSCs) to repair bone defects of spontaneously hypertensive rats (SHR). First, we evaluated SHR in terms of bone morphometry and differentiation of MSCs into osteoblasts. Then, the effects of the interactions between MSCs from normotensive rats (NTR-MSCs) cocultured with SHR (SHR-MSCs) on the osteoblast differentiation of both cell populations were evaluated. Also, bone formation into calvarial defects of SHR treated with NTR-MSCs was analyzed. Hypertension induced bone loss evidenced by reduced bone morphometric parameters of femurs of SHR compared with NTR as well as decreased osteoblast differentiation of SHR-MSCs compared with NTR-MSCs. NTR-MSCs partially restored the capacity of SHR-MSCs to differentiate into osteoblasts, while SHR-MSCs exhibited a slight negative effect on NTR-MSCs. An enhanced bone repair was observed in defects treated with NTR-MSCs compared with control, stressing this cell therapy efficacy even in bones damaged by hypertension. The use of MSCs derived from a heathy environment can be in the near future a smart approach to treat bone loss in the context of regenerative dentistry for oral rehabilitation of hypertensive patients.