Enhanced Bone Regeneration and Bone Defect Repair Using Magnesium/Lithium-Co-Modified, Porous, Hydroxyapatite Composite Scaffolds

2020 ◽  
Vol 12 (1) ◽  
pp. 124-136
Author(s):  
Hai-Yan Zhao ◽  
Releken-Yeersheng ◽  
Ya-Yi Xia ◽  
Xing-Wen Han ◽  
Chao Zhang ◽  
...  
Keyword(s):  
Bone Regeneration ◽  
Bone Defect ◽  
Biological Degradation ◽  
Porous Hydroxyapatite ◽  
Bone Defect Repair ◽  
Hydroxyapatite Composite ◽  
Defect Repair ◽  
Osteogenic Effect

Background: Hydroxyapatite (HA) has been frequently used in clinic, but it is hard to be degraded, and insufficient in osteogenesis and angiogenesis. This study aimed to modify HA by doping magnesium/lithium (Mg/Li) and assess the Mg/LiHA scaffold's bone regeneration and bone defect repair effects. Materials and Methods: The biomaterial was identified using XRD, FTIR and SEM. The porosity, cell mediated degradation behavior and mechanical property were investigated. Meanwhile, cell proliferation and adhesion were also exploited. Finally, osteogenic effect of Mg/LiHA scaffold in vitro, and bone defect repair effect in vivo were researched. Results: The results suggested that low-content of Mg/Li incorporation did not influence on the structure of HA. The cells mediated degradation experiments indicated that Mg/Li doped HA could improve the biological degradation and release the Mg2+ and Li+ sustainedly. The compressive strength of Mg/LiHA scaffolds with 63% porosity reached to 3.9 MPa. Cells proliferation and adhesion experiments demonstrated that Mg/LiHA scaffolds were beneficial to cell growth and attachment. Furthermore, Mg/LiHA scaffolds increased ALP expression, calcium phosphate deposition and VEGF expression in vitro. The bone defect repair in vivo was enhanced by using Mg/LiHA scaffolds. Conclusion: Mg/Li-co-substituted HA could enhance bone regeneration and bone defect repair, and may be recommended to further research on bone defect repair.

scholarly journals Increased BMSC Exosomal miR-140-3p Alleviates Bone Degradation and Promotes Bone Restoration by Targeting Plxnb1 in Diabetic Rats

2021 ◽  
Author(s):  
Ning Wang ◽  
Xuanchen Liu ◽  
Zhen Tang ◽  
Xinghui Wei ◽  
Hui Dong ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Bone Formation ◽  
Bone Regeneration ◽  
Bone Defect ◽  
Diabetic Rats ◽  
Osteogenic Potential ◽  
Bone Degradation ◽  
Defect Repair

Abstract Background: Diabetes mellitus (DM) is considered to be an important factor for bone degeneration disorders such as bone defect nonunion, which is characterized by physical disability and tremendous economy cost to families and society. Exosomal miRNAs of BMSCs have been reported to participate in osteoblastogenesis and modulating bone formation. However, their impacts on the development of bone degeneration in DM are not yet known. The role of miRNAs in BMSCs exosomes on regulating hyperglycemia bone degeneration was investigated in the present study. Results: The osteogenic potential in bone defect repair of exosomes derived from diabetes mellitus BMSCs derived exosomes (DM-Exos) were revealed to be lower than that in normal BMSCs derived exosomes (N-Exos) in vitro and in vivo. Here, we demonstrate that miR-140-3p level was significantly altered in exosomes derived from BMSCs, ADSCs and serum from DM rats. In in vitro experiments, upregulated miR-140-3p exosomes promoted DM BMSCs differentiation into osteoblasts. The effects were exerted by miR-140-3p targeting plxnb1, plexin B1 is the receptor of semaphoring 4D(Sema4D) that inhibited osteocytes differentiation, thereby promoting bone formation. In DM rats with bone defect, miR-140-3p upregulated exosomes were transplanted into injured bone and accelerated bone regeneration. Besides, miR-140-3p in the exosomes was transferred into BMSCs and osteoblasts and promoted bone regeneration by targeting the plexin B1/RohA/ROCK signaling pathway. Conclusions: Normal-Exos and miR-140-3p overexpressed-Exos accelerated diabetic wound healing by promoting the osteoblastogenesis function of BMSCs through inhibition plexin B1 expression which is the receptor of Sema4D and the plexin B1/RhoA/ROCK pathway compared with diabetes mellitus-Exos. This offers a new insight and a new therapy for treating diabetic bone unhealing.

scholarly journals In Vivo and in Vitro Studies of the Effect of Chitosan on the Bone Defect Repair Process

2016 ◽  
Vol 16 (2) ◽  
pp. 171-179 ◽  
Author(s):  
I. V. Zudina ◽  
◽  
A. P. Vedyaeva ◽  
P. V. Ivanov ◽  
A. F. A. Alzubaidi ◽  
...  
Keyword(s):  
Bone Defect ◽  
Repair Process ◽  
In Vitro Studies ◽  
Bone Defect Repair ◽  
Defect Repair

scholarly journals Tuning filament composition and microstructure of 3D-printed bioceramic scaffolds facilitate bone defect regeneration and repair

2021 ◽  
Vol 8 (2) ◽  
Author(s):  
Yi Chen ◽  
Jiaping Huang ◽  
Jiamei Liu ◽  
Yingming Wei ◽  
Xianyan Yang ◽  
...  
Keyword(s):  
3D Printing ◽  
Bone Defect ◽  
Core Shell ◽  
Shell Layer ◽  
Ion Release ◽  
Component Distribution ◽  
Bone Defect Repair ◽  
Defect Repair

Abstract It is still a challenge to optimize the component distribution and microporous structures in scaffolds for tailoring biodegradation (ion releasing) and enhancing bone defect repair within an expected time stage. Herein, the core–shell-typed nonstoichiometric wollastonite (4% and 10% Mg-doping calcium silicate; CSiMg4, CSiMg10) macroporous scaffolds with microporous shells (adding ∼10 μm PS microspheres into shell-layer slurry) were fabricated via 3D printing. The initial mechanical properties and bio-dissolution (ion releasing) in vitro, and osteogenic capacity in vivo of the bioceramic scaffolds were evaluated systematically. It was shown that endowing high-density micropores in the sparingly dissolvable CSiMg10 or dissolvable CSiMg4 shell layer inevitably led to nearly 30% reduction of compressive strength, but such micropores could readily tune the ion release behaviour of the scaffolds (CSiMg4@CSiMg10 vs. CSiMg4@CSiMg10-p; CSiMg10@CSiMg4 vs. CSiMg10@CSiMg4-p). Based on the in rabbit femoral bone defect repair model, the 3D μCT reconstruction and histological observation demonstrated that the CSiMg4@CSiMg10-p scaffolds displayed markedly higher osteogenic capability than the other scaffolds after 12 weeks of implantation. It demonstrated that core–shell bioceramic 3D printing technique can be developed to fabricate single-phase or biphasic bioactive ceramic scaffolds with accurately tailored filament biodegradation for promoting bone defect regeneration and repair in some specific pathological conditions.

scholarly journals Mitochondria transfer enhances bone marrow mesenchymal stem cell functions and promotes bone defect healing

2020 ◽  
Author(s):  
Yusi Guo ◽  
Xiaopei Chi ◽  
Yifan Wang ◽  
Boon Chin Heng ◽  
Yan Wei ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Bone Defect ◽  
Atp Production ◽  
Bone Defect Repair ◽  
Mitochondria Transfer ◽  
Defect Repair

Abstract Background: Bone marrow-derived mesenchymal stem cells (BMSCs) transplantation is considered a promising therapeutic approach for bone defect repair. However, during the transplantation procedure, the functions and viability of BMSCs may be impaired due to extended durations of in vitro culture, aging and disease conditions of patients. Inspired by spontaneous intercellular mitochondria transfer that naturally occurs within injured tissues to rescue cellular or tissue function, we investigated whether artificial mitochondria transfer into pre-transplant BMSCs in vitro could improve cellular function and enhance their therapeutic effects on bone defect repair in situ. Methods: First, mitochondria were isolated from donor BMSCs and transferred into recipient BMSCs of the same passage. Afterwards, changes in proliferative capability was evaluated by Cell Counting Kit-8, Ki67 staining, etc., while Transwell, wound scratch healing and cell motility tests were conducted to determine migration ability. Then, alkaline phosphatase (ALP) staining, Alizarin Red staining, combined with qPCR and Western Blot experiments of Runx2 and BMP2 were performed to elucidate the effect of mitochondria transfer on the osteogenic potential of BMSCs in vitro. After that, the in vivo experiments were completed by transplanting mitochondria-recipient BMSCs into a rat cranial critical-size bone defect model. Micro CT scanning and histological analysis were conducted 4 weeks and 8 weeks after transplantation to evaluate the osteogenesis effect in situ. Finally, in order to discover the potential connection between cellular behavioral changes and aerobic metabolism, OXPHOS (oxidative phosphorylation) and ATP production were assessed and inhibition of aerobic respiration by oligomycin was proceeded. Results: Mitochondria-recipient BMSCs exhibited significantly enhanced proliferation and migration, and increased osteogenic differentiation upon osteogenic induction. The in vivo results showed more new bone formation after transplantation of mitochondria-recipient BMSCs in situ. Increased OXPHOS activity and ATP production were further observed, whereas the inhibition of which impaired the enhancement of proliferation, migration and osteogenic differentiation induced by mitochondria transfer. Conclusions: Mitochondria transfer is a feasible technique to enhance BMSCs function in vitro and promote bone defect repair in situ through the up-regulation of aerobic metabolism. The results indicated that mitochondria transfer may be a novel promising technique for optimizing stem cell function.

scholarly journals Mitochondria transfer enhances proliferation, migration, and osteogenic differentiation of bone marrow mesenchymal stem cell and promotes bone defect healing

2020 ◽  
Author(s):  
Yusi Guo ◽  
Xiaopei Chi ◽  
Yifan Wang ◽  
Boon Chin Heng ◽  
Yan Wei ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Bone Defect ◽  
Atp Production ◽  
Bone Defect Repair ◽  
Mitochondria Transfer ◽  
Defect Repair

Abstract Background: Bone marrow-derived mesenchymal stem cells (BMSCs) transplantation is considered a promising therapeutic approach for bone defect repair. However, during the transplantation procedure, the functions and viability of BMSCs may be impaired due to extended durations of in vitro culture, aging and disease conditions of patients. Inspired by spontaneous intercellular mitochondria transfer that naturally occurs within injured tissues to rescue cellular or tissue function, we investigated whether artificial mitochondria transfer into pre-transplant BMSCs in vitro could improve cellular function and enhance their therapeutic effects on bone defect repair in situ . Methods: Mitochondria were isolated from donor BMSCs and transferred into recipient BMSCs of the same batch and passage. Subsequently, changes in proliferative capacity and cell senescence were evaluated by live cell imaging, Cell Counting Kit-8 assay, cell cycle analysis, Ki67 staining, qPCR and Western Blot analysis of C-myc expression, and β-galactosidase staining. Migration ability was evaluated by the transwell migration assay, wound scratch healing and cell motility tests. Alakine phosphatase (ALP) staining, Alizarin Red staining, combined qPCR and Western Blot analyses of Runx2 and BMP2 were performed to elucidate the effects of mitochondria transfer on the osteogenic potential of BMSCs in vitro . After that, in vivo experiments were performed by transplanting mitochondria-recipient BMSCs into a rat cranial critical-size bone defect model. Micro CT scanning and histological analysis were conducted at 4 and 8 weeks after transplantation to evaluate osteogenesis in situ . Finally, in order to establish the correlation between cellular behavioral changes and aerobic metabolism, OXPHOS (oxidative phosphorylation) and ATP production were assessed and inhibition of aerobic respiration by oligomycin was performed. Results: Mitochondria-recipient BMSCs exhibited significantly enhanced proliferation and migration, and increased osteogenesis upon osteogenic induction. The in vivo results showed more new bone formation after transplantation of mitochondria-recipient BMSCs in situ . Increased OXPHOS activity and ATP production were observed, which upon inhibition by oligomycin attenuated the enhancement of proliferation, migration and osteogenic differentiation induced by mitochondria transfer. Conclusions: Mitochondria transfer is a feasible technique to enhance BMSCs function in vitro and promote bone defect repair in situ through the up-regulation of aerobic metabolism. The results indicated that mitochondria transfer may be a novel promising technique for optimizing stem cell therapeutic function.

scholarly journals Cobalt-doped bioceramic scaffolds fabricated by 3D printing show enhanced osteogenic and angiogenic properties for bone repair

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Jungang Li ◽  
Chaoqian Zhao ◽  
Chun Liu ◽  
Zhenyu Wang ◽  
Zeming Ling ◽  
...  
Keyword(s):  
Compressive Strength ◽  
3D Printing ◽  
Bone Regeneration ◽  
Doping Concentration ◽  
Artificial Bone ◽  
Bone Defect Repair ◽  
Co Doping ◽  
Defect Repair ◽  
Co Doped

Abstract Background The bone regeneration of artificial bone grafts is still in need of a breakthrough to improve the processes of bone defect repair. Artificial bone grafts should be modified to enable angiogenesis and thus improve osteogenesis. We have previously revealed that crystalline Ca10Li(PO4)7 (CLP) possesses higher compressive strength and better biocompatibility than that of pure beta-tricalcium phosphate (β-TCP). In this work, we explored the possibility of cobalt (Co), known for mimicking hypoxia, doped into CLP to promote osteogenesis and angiogenesis. Methods We designed and manufactured porous scaffolds by doping CLP with various concentrations of Co (0, 0.1, 0.25, 0.5, and 1 mol%) and using 3D printing techniques. The crystal phase, surface morphology, compressive strength, in vitro degradation, and mineralization properties of Co-doped and -undoped CLP scaffolds were investigated. Next, we investigated the biocompatibility and effects of Co-doped and -undoped samples on osteogenic and angiogenic properties in vitro and on bone regeneration in rat cranium defects. Results With increasing Co-doping level, the compressive strength of Co-doped CLP scaffolds decreased in comparison with that of undoped CLP scaffolds, especially when the Co-doping concentration increased to 1 mol%. Co-doped CLP scaffolds possessed excellent degradation properties compared with those of undoped CLP scaffolds. The (0.1, 0.25, 0.5 mol%) Co-doped CLP scaffolds had mineralization properties similar to those of undoped CLP scaffolds, whereas the 1 mol% Co-doped CLP scaffolds shown no mineralization changes. Furthermore, compared with undoped scaffolds, Co-doped CLP scaffolds possessed excellent biocompatibility and prominent osteogenic and angiogenic properties in vitro, notably when the doping concentration was 0.25 mol%. After 8 weeks of implantation, 0.25 mol% Co-doped scaffolds had markedly enhanced bone regeneration at the defect site compared with that of the undoped scaffold. Conclusion In summary, CLP doped with 0.25 mol% Co2+ ions is a prospective method to enhance osteogenic and angiogenic properties, thus promoting bone regeneration in bone defect repair.

scholarly journals Construction of hollow polydopamine nanoparticle based drug sustainable release system and its application in bone regeneration

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Lu Wang ◽  
Shuwei Liu ◽  
Chunxia Ren ◽  
Siyuan Xiang ◽  
Daowei Li ◽  
...  
Keyword(s):  
Bone Regeneration ◽  
Bone Defect ◽  
Load Capacity ◽  
Good Prospect ◽  
Alizarin Red ◽  
Drug Load ◽  
Load Rate ◽  
Low Toxicity

AbstractNanomaterial-based drug sustainable release systems have been tentatively applied to bone regeneration. They, however, still face disadvantages of high toxicity, low biocompatibility, and low drug-load capacity. In view of the low toxicity and high biocompatibility of polymer nanomaterials and the excellent load capacity of hollow nanomaterials with high specific surface area, we evaluated the hollow polydopamine nanoparticles (HPDA NPs), in order to find an optimal system to effectively deliver the osteogenic drugs to improve treatment of bone defect. Data demonstrated that the HPDA NPs synthesized herein could efficiently load four types of osteogenic drugs and the drugs can effectively release from the HPDA NPs for a relatively longer time in vitro and in vivo with low toxicity and high biocompatibility. Results of qRT-PCR, ALP, and alizarin red S staining showed that drugs released from the HPDA NPs could promote osteogenic differentiation and proliferation of rat bone marrow mesenchymal stem cells (rBMSCs) in vitro. Image data from micro-CT and H&E staining showed that all four osteogenic drugs released from the HPDA NPs effectively promoted bone regeneration in the defect of tooth extraction fossa in vivo, especially tacrolimus. These results suggest that the HPDA NPs, the biodegradable hollow polymer nanoparticles with high drug load rate and sustainable release ability, have good prospect to treat the bone defect in future clinical practice.

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