Frontiers in Bioengineering and Biotechnology
·
2025
·
IF 4.8
Yong Zhang,Junxian Ren,Zongshan Shen,Jiayu Yang,Jichen Yang,Zhengmei Lin,Xuetao Shi,Chuanjiang Zhao,Juan Xia
Introduction: Periodontitis leads to the degradation of tooth-supporting tissues, ultimately causing tooth mobility and loss. Guided tissue regeneration (GTR) surgery employs barrier membranes to facilitate tissue regeneration. However, conventional membranes lack bone-inducing properties, thereby limiting their efficacy. Our objective was to develop a bifunctional GTR membrane that combines mechanical stability with bone-inducing capabilities. To achieve this, we engineered BMP2 peptide-modified polycaprolactone-collagen nanosheets (BPCNs) to enhance periodontal regeneration by improving cell adhesion, osteogenesis, and anti-inflammatory activity.Methods: BPCNs with nanoscale thickness were fabricated using the spin-coating technique, incorporating BMP2 peptides, collagen, polycaprolactone (PCL), and polyvinyl alcohol (PVA). Successful conjugation of BMP2 to the BPCNs was verified through UV spectrophotometry and confocal laser scanning microscopy. The biocompatibility and cell adhesion properties of BPCNs were rigorously assessed using CCK-8 assays, microscopic imaging, and quantitative cell counting. In vitro osteogenic efficacy was evaluated by Alizarin Red S (ARS) staining and quantitative reverse transcription polymerase chain reaction (qRT-PCR) to analyze osteogenic marker gene expression. A rat periodontal defect model was established to assess in vivo regenerative performance, with outcomes analyzed through micro-CT, hematoxylin-eosin (H&E) staining, and Masson’s trichrome staining, confirming enhanced tissue regeneration and the absence of systemic toxicity. The mechanistic pathways underlying BPCNs-mediated regeneration were elucidated via RNA sequencing (RNA-seq), revealing the activation of osteogenic signaling cascades and the suppression of proinflammatory pathways.Results: BPCNs demonstrated excellent biocompatibility, promoted fibroblast and bone marrow stem cell (BMSC) adhesion, and enhanced BMSC osteogenesis. Furthermore, BPCNs significantly promoted periodontal tissue regeneration in a rat model. Mechanistically, RNA-seq analysis revealed that BPCNs upregulated genes involved in tissue regeneration and downregulated proinflammatory pathways.Discussion: This study introduced a novel osteoinductive nanosheet, termed BPCNs, which provides a groundbreaking material-based approach for the regenerative repair of periodontal tissue defects. These findings position BPCNs as a highly promising candidate for GTR surgery, with significant potential to improve clinical outcomes in periodontal regenerative medicine.
研究领域:
口腔医学
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再生医学
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材料科学
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产品关联
DOI
PubMed
高影响因子
American Journal of Translational Research
·
2021
·
IF 4.06
Jinlong Chen,Yishan Yang
Objective: To determine whether long-chain non-coding RNA (lncRNA) HAGLR can regulate BMP2 by absorbing microRNA-214-3p (miR-214-3p), and to explore its role and mechanism in tibial fracture (TF) healing. Methods: The HAGLR, miR-214-3p, and BMP2 expression levels in TF and in adjacent normal tissues were measured using quantitative real-time polymerase chain reaction (qRT-PCR). MC3T3-E1 osteoblasts were used to construct the in vitro model. HAGLR was localized subcellularly through RNA-fluorescence in situ hybridization (FISH). A dual-luciferase report experiment confirmed that miR-214-3p has a targeted relationship with HAGLR and BMP2. It was then divided into a HAGLR over-expression group, an miR-214-3p mimic group, a HAGLR+miR-214-3p mimic group, an sh-HAGLR group, a BMP over-expression group, an sh-HAGLR+over-expression BMP2 group, and a negative control group. The proliferation and apoptosis of the MC3T3-E1 osteoblasts were examined using MTT assays and flow cytometry. A TF model was established in male C57BL/6J mice. The serum alkaline phosphatase (ALP) and osteoprotegerin (OPG) levels in the sham group, the TF group, and the TF group that were injected with HAGLR were compared using ELISA. Hematoxylin-eosin (HE) staining was used to confirm the fracture healing in the mouse model. Results: Compared with the adjacent normal tissues in the TF patients, the HAGLR and BMP2 expressions decreased but the miR-214-3p expressions increased in the TF tissues ( P <0.05). HAGLR, an endogenous sponge, absorbed the miR-214-3p, and the BMP2 expression was directly regulated by miR-214-3p. HAGLR increased the proliferative activity of the osteoblasts and decreased the apoptosis rate. The over-expression of miR-214-3p partly reversed the effect of HAGLR on the cells, decreased the proliferative activity, and increased the apoptosis rate (all P <0.05). The sh-HAGLR decreased the proliferative activity and increased the apoptosis rate. But after the over-expression of BMP2, the proliferative activity of the cells was higher, and the apoptosis rate was lower than it was in the sh-HAGLR group (all P <0.05). The over-expression of HAGLR can up-regulate the ALP and OPG levels in mouse models ( P <0.05). Conclusion: lncRNA HAGLR can regulate BMP2 to play a protective role in TF by absorbing miR-214-3p, and it is related to promoting the osteoblast proliferation, inhibiting apoptosis, and up-regulating the serum ALP and OPG levels to accelerate bone healing.
研究领域:
分子生物学
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骨科
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再生医学
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产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2020
·Vol. 8
·期 30
·6378-6389
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IF 5.344
Zhuo Liang,Yue Luo,Yonggang Lv
A demineralized bone matrix (DBM) scaffold has good biocompatibility, low antigenicity, a natural porous structure and no cytotoxicity, and so it is an appropriate material for bone regeneration. However, osteoinductive growth factors are often removed during preparation, which destroys the osteoinductive capacity of the DBM scaffold. Biomaterials combined with gene therapy is a promising approach to effectively avoid this adverse side effect. This study develops a human bone morphogenetic protein 2 (hBMP2) gene-activated DBM scaffold to enhance the osteoinductive capacity of DBM and improve bone repair. Bone marrow mesenchymal stem cell (MSC)-derived microvesicles (MVs) were obtained, and polyethyleneimine (PEI) and human bone morphogenetic protein 2 (hBMP2) plasmids (phBMP2) were sequentially coated on the MVs by layer-by-layer (LBL) self-assembly to form an MVs–PEI/phBMP2 non-viral gene vector. Finally, the gene-activated scaffold (DBM/MVs–PEI/phBMP2) was prepared by loading MVs–PEI/phBMP2 onto a DBM scaffold. The experimental results show that the MVs–PEI/phBMP2 exhibits higher transfection efficiency and lower cytotoxicity to MSCs when the MVs/PEI weight ratio = 5, and could enhance the osteogenic differentiation of MSCs in vitro. Subcutaneous implantation into rats showed that the DBM/MVs–PEI/phBMP2 scaffold could efficiently enhance the deposition of: collagen fibers, osteocalcin, osteopontin and CD34 endogenous proteins. Rabbit femoral condyle defect experiments proved that the DBM/MVs–PEI/phBMP2 scaffold could significantly promote bone repair. This study presents a novel, highly efficient and low cytotoxicity gene delivery vector based on MVs. The gene-activated DBM scaffold based on MVs not only could promote bone formation but also angiogenesis, implying that this kind of gene-activated scaffold is a promising bone substitute material.
研究领域:
组织工程
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再生医学
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基因治疗
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生物材料
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产品关联
DOI
PubMed
高影响因子
Scientific Reports
·
2020
·Vol. 10
·期 1
·1-7
·
IF 3.998
Wang Xueni,Liao Xiuling,Zhang Yimin,Wei Linyao,Pang Yuzhou
Schisandrin B (SchB) is the highest content of biphenyl cyclooctene lignans in Schisandra chinensis . It has been reported to have a variety of pharmacological effects, including anti-inflammatory, anti-oxidant, anti-cancer, heart protection, liver protection. In this study, we found that SchB can promote the proliferation of MC3T3-E1 subclone 14 cells. Meanwhile, we found that SchB can regulate the BMP2-SMADs signaling pathway by increasing gene and protein expression of those relative biomolecules. Furthermore, SchB can raise the RUNX2 and SP7 expression in both mRNA and protein levels. Since the role of BMP2-SMADs-RUNX2-SP7 signaling axis in osteoblast proliferation and differentiation has been well documented. The present experimental findings indicate that SchB could promote the proliferation and differentiation of osteoblasts through BMP2-SMADs-RUNX2-SP7 signaling axis.
研究领域:
药理学
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细胞生物学
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分子生物学
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DOI
PubMed
高影响因子
COMPOSITES SCIENCE AND TECHNOLOGY
·
2016
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IF 3.897
Ting Kang,Xiaoli Hua,Peiqing Liang,Minyu Rao,Qin Wang,Changyun Quan,Chao Zhang,Qing Jiang
To be better used as implant materials in bone regeneration, bioactivity and osteogenesis of poly(methyl methacrylate) (PMMA)-based bone cement need to be further enhanced. In this study, bioactive hydroxyapatite (HA) nanoparticle decorated with polydopamine (pDA) and BMP2 mimicking peptide (serine-serine-valine-proline-threonine, SSVPT) was incorporated into PMMA-based cement (p x -HA/PMMA). The presence of pDA layer on HA surface could keep the mechanical property of p x -HA/PMMA cements comply with the requirement of clinical application. More importantly, the p x -HA/PMMA cement exhibited excellent biomechanical property with enhanced interfacial adhesion between cement and swine femur. Biomineralization and cell experiment in vitro showed that the incorporation of pDA-coated HA and SSVPT can synergistically enhance the bioactivity of p x -HA/PMMA cement for regeneration and provide an attractive strategy to reconstruction of load-bearing bone.
研究领域:
生物材料学
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骨再生医学
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产品关联
DOI
高影响因子
Journal of Materials Chemistry B
·
2022
·Vol. 10
·期 32
·6214-6227
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IF 7.571
Xu Zhang,Jian Li,Jin Chen,Zi-Xin Peng,Jiang-Nan Chen,Xinyi Liu,Fuqing Wu,Peng Zhang,Guo-Qiang Chen
The hierarchical three-dimensional (3D)-printing scaffolds based on microbial polyester poly(3-hydroxybutyrate-co-4-hydroxybutyrate) (P34HB) were designed and used for bone tissue engineering via surface functionalization on 3D-printed (P34HB) scaffolds using polydopamine (PDA)-mediated recombinant human bone morphogenetic protein-2 (BMP2), leading to enhanced bone formation in a rat model with a calvarial critical-size bone defect. Taking advantage of the adhesive property of PDA under alkaline and aerobic conditions, osteogenic BMP2 was captured on the surface of PHA scaffolds, resulting in their enhanced osteogenic bioactivity, better stem cell adhesion and proliferation, and sustainable release of a bioactive substance over a period of 30 days. These contributed to notable differences in alkaline phosphatase (ALP) activity, mineralization, expressions of osteogenesis-related genes, as well as finally enhanced in vivo bone formation in rats. The functionalized 3D-printed P34HB scaffolds via the PDA-mediated osteogenic activity were developed as a versatile platform for bone tissue regeneration.
研究领域:
组织工程
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生物医用材料
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骨再生
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生物技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nanotechnology Reviews
·
2021
·Vol. 10
·期 1
·870-882
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IF 7.848
Qiuyang Zhang,Li Zhang,Minhui Yang,Qingxiang Hong,Zhongmei Yang,Sen Liu,Qingping Xiong,Changjiang Pan
As biodegradable orthopedic implant materials, magnesium alloys have been attracted enough attentions recently. However, too fast degradation in vivo , limited biocompatibilities, and insufficient antibacterial properties are three main challenges at present. In order to solve these problems, a multifunctional composite coating of Chi(Zn/BMP2)/HA was constructed on AZ31B magnesium alloy surface, successively by the alkali heating treatment, self-assembly of 16-phosphonyl-hexadecanoic acid, in situ immobilization of Chi(Zn/BMP2) (chitosan, zinc ions, and bone morphogenetic protein 2), and the deposition of HA (hydroxyapatite). The results of ATR-FTIR (attenuated total reflection Fourier transform infrared spectrum) spectra and elemental compositions confirmed that 16-phosphonyl-hexadecanoic acid, Chi(Zn/BMP2), and HA were successfully immobilized on the surface. Compared with Mg, Mg-OH, Mg-16, and Mg-Chi(Zn/BMP2), Mg-Chi(Zn/BMP2)/HA with the concave–convex structure surface significantly enhanced the hydrophilicity and corrosion resistance. On the other hand, Mg-Chi(Zn/BMP2)/HA coating also showed excellent biocompatibilities, which not only significantly promoted the osteoblast adhesion and proliferation, but also upregulated ALP and OCN expression of osteoblasts. Furthermore, due to the synergistic antibacterial effect of zinc ions and chitosan, Mg-Chi(Zn/BMP2)/HA showed a good antibacterial property against Escherichia coli ( E. coli ). Therefore, it can be said that the method used in this work has a good application prospect in improving the corrosion resistance, biocompatibility of magnesium alloys, and inhibiting infections against E. coli .
研究领域:
材料科学
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生物医学工程
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表面工程
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产品关联
DOI
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2019
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IF 3.743
Xiao-Jun Chen,Ying-Shan Shen,Min-Cong He,Fan Yang,Peng Yang,Feng-Xiang Pang,Wei He,Yan-ming Cao,Qiu-Shi Wei
Steroid-induced osteonecrosis of the femoral head (SONFH) is a refractory disease induced by glucocorticoids. Marrow mesenchymal stem cells (MSCs) differentiate into multiple bone matrix cells and have been used as cell-based therapies to treat ONFH. However, the osteogenesis of MSCs isolated from patients with SONFH is significantly decreased. Polydatin has been widely used in traditional Chinese remedies due to its multiple pharmacological actions. As shown in our previous study, Polydatin protects from oxidative stress and promotes BMSC migration. However, little is known about its role in BMSC (Bone marrow mesenchymal stem cells) osteogenesis; therefore, we further investigated the effect and mechanism of Polydatin in hBMSC osteogenesis. The ability of Polydatin to promote the proliferation and osteogenic differentiation of hBMSCs was determined using the MTT assay, ALP staining and the ALP activity assay. Next, qPCR and western blotting were performed to measure the levels of genes and proteins related to the osteogenesis of hBMSCs. Then, the effect of Polydatin on the nuclear translocation of β-catenin was determined using immunofluorescence staining. Polydatin (30 μM) markedly enhanced the proliferation of hBMSCs and alkaline phosphatase (ALP) activity. Additionally, it also significantly upregulated the expression of osteogenic genes (Runx2, osteopontin, DLX5, osteocalcin, collagen type I and BMP2) and components of the Wnt signaling pathway (β-catenin, Lef1, TCF7, c-jun, c-myc and cyclin D). These osteogenesis-potentiating effects of Polydatin were blocked by Noggin, an inhibitor of the BMP pathway, and DKK1, an inhibitor of the Wnt/β-catenin pathway. However, DKK1 did not affect Polydatin-induced BMP2 expression. Based on our results, Polydatin promotes the proliferation and osteogenic differentiation of hBMSCs through the BMP2-Wnt/β-catenin signaling pathway.
研究领域:
药理学
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干细胞研究
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骨科
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Stem Cell Research & Therapy
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2020
·Vol. 11
·期 1
·1-15
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IF 5.116
Shen Ying-Shan,Chen Xiao-Jun,Wuri Sha-Na,Yang Fan,Pang Feng-Xiang,Xu Liang-Liang,He Wei,Wei Qiu-Shi
Objectives Polydatin (PD), extracted from Polygonum cuspidatum , has shown potential therapeutic applications due to its antiosteoporotic and anti-inflammatory activities. Our previous study suggested that PD promotes the osteogenesis of human bone marrow stromal cells (hBMSCs) via the BMP2-Wnt/β-catenin pathway. The aim of our present study was to further explore the role of PD-mediated regulation of Tafazzin (TAZ), a transcriptional coactivator with a PDZ-binding motif, in osteogenesis. Materials and methods hBMSCs were isolated and treated with PD at various concentrations. Alizarin red staining and RT-qPCR were performed to identify calcium complex deposition in hBMSCs as well as the expression of specific osteoblast-related markers, respectively, in each group. Next, TAZ-silenced hBMSCs were generated by lentivirus-produced TAZ shRNA. After treatment with PD, the osteogenic abilities of the TAZ-silenced and control hBMSCs were estimated by ALP activity assay, and expression of the TAZ protein was detected by Western blot analysis and immunofluorescence staining. In vitro, an ovariectomized (OVX) mouse model was established and used to evaluate the effect of PD on bone destruction by micro-CT, immunohistochemistry, and ELISA. Results In vitro, 30 μM PD significantly improved the proliferation and calcium deposition of hBMSCs and markedly stimulated the expression of the mRNAs RUNX2 , Osteopontin , DLX5 , β-catenin , TAZ , and Osteocalcin ( OCN ). Osteogenic differentiation induced by PD was blocked by lentivirus-mediated TAZ shRNA. Furthermore, Noggin (a regulator of bone morphogenic protein 2 (BMP2)) and DKK1 (an inhibitor of the Wnt/β-catenin pathway) were found to inhibit the increase in TAZ expression induced by PD. In vivo, PD prevented estrogen deficiency-induced bone loss in the OVX mouse model. Conclusion Taken together, our findings suggest that PD improved the osteogenic differentiation of hBMSCs and maintained the bone matrix in the OVX mouse model through the activation of TAZ, a potential target gene of the BMP2-Wnt/β-catenin pathway.
研究领域:
药理学
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干细胞生物学
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骨骼生物学
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分子生物学
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DOI
PubMed
高影响因子
Stem Cell Research & Therapy
·
2019
·Vol. 10
·期 1
·1-11
·
IF 4.627
Kong Yuanyuan,Hu Xiaoli,Zhong Yingqun,Xu Ke,Wu Buling,Zheng Jianmao
Background Magnesium (Mg 2+ )-enriched microenvironment promotes odontogenic differentiation in human dental pulp stem cells (DPSCs), but the regulatory mechanisms remain undefined. The aim of this work was to assess magnesium’s function in the above process and to explore the associated signaling pathway. Methods DPSCs underwent culture in odontogenic medium with the addition of 0, 1, 5, or 10 mM MgCl 2 . Intracellular Mg 2+ levels in DPSCs were evaluated flow cytometrically using Mag-Fluo-4-AM. Mg 2+ -entry was inhibited by TRPM7 inhibitor 2-aminoethoxydiphenyl borate (2-APB). RNA-Sequencing was carried out for assessing transcriptome alterations in DPSCs during odontogenic differentiation associated with high extracellular Mg 2+ . KEGG pathway analysis was performed to determine pathways related to the retrieved differentially expressed genes (DEGs). Immunoblot was performed for assessing magnesium’s role and exploring ERK/BMP2/Smads signaling. Results Mg 2+ -enriched microenvironment promoted odontogenic differentiation in DPSCs via intracellular Mg 2+ increase. Consistently, the positive effect of high extracellular Mg 2+ on odontogenic differentiation in DPSCs was blocked by 2-APB, which reduced Mg 2+ entry. RNA-sequencing identified 734 DEGs related to odontogenic differentiation in DPSCs in the presence of high extracellular Mg 2+ . These DEGs participated in many cascades such as MAPK and TGF-β pathways. Consistently, ERK and BMP2/Smads pathways were activated in DPSCs treated with high extracellular Mg 2+ . In agreement, ERK signaling inhibition by U0126 blunted the effect of high extracellular Mg 2+ on mineralization and odontogenic differentiation in DPSCs. Interestingly, BMP2, BMPR1, and phosphorylated Smad1/5/9 were significantly decreased by U0126, indicating that BMP2/Smads acted as downstream of ERK. Conclusions Mg 2+ -enriched microenvironment promotes odontogenic differentiation in DPSCs by activating ERK/BMP2/Smads signaling via intracellular Mg 2+ increase. This study revealed that Mg 2+ -enriched microenvironment could be used as a new strategy for dental pulp regeneration.
研究领域:
牙科研究
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干细胞生物学
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分子生物学
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细胞信号传导
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产品关联
DOI
PubMed
高影响因子
Small
·
2022
·Vol. 18
·期 23
·2201123
·
IF 15.153
Jing Li,Yao Zhang,Zhichao Lou,Mingxi Li,Lin Cui,Zhenrong Yang,Lijuan Zhang,Yu Zhang,Ning Gu,Fang Yang
Neural stem cells (NSCs) are used to treat various nervous system diseases because of their self-renewal ability and multidirectional differentiation potential. However, an insufficient ability to track their migration in vivo and poor control over their survival and differentiation efficiency are two major critical challenges for clinical application. Here, it is shown that when magnetic nanobubbles (MNBs), which are assembled from magnetic nanoparticles, are internalized by NSCs, intramembrane volumetric oscillation of the MNBs induces an increase in intracellular hydrostatic pressure and cytoskeleton force, resulting in the activation of the Piezo1-Ca 2+ mechanosensory channel. This subsequently triggers the BMP2/Smad biochemical signaling pathway, leading to differentiation of NSCs into the neuronal phenotype. Signaling through the Piezo1-Ca 2+ -BMP2/Smad pathway can be further accelerated by application of an external shear stress force using low-intensity pulsed ultrasound. More importantly, magnetic resonance imaging and ultrasound imaging surveillance of NSCs based on MNB labeling can be leveraged to provide NSC therapeutic outcomes. Both the in vitro and in vivo findings demonstrate that a bubble nanostructure-induced physical force can modulate and control the mechanical signaling pathway regulating stem cell development.
研究领域:
神经科学
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生物医学工程
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干细胞生物学
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医学影像学
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力学生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Materials Science & Engineering C-Materials for Biological Applications
·
2018
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IF 5.08
Linawati Sutrisno,Yan Hu,Xinkun Shen,Menghuan Li,Zhong Luo,Liangliang Dai,Sixiang Wang,Julia Li Zhong,Kaiyong Cai
Infection associated with orthopedic implants is the chief cause of implant failure. An important consideration to prevent the infection at implants is to inhibit the biofilm formation for the initial 6 h. Therefore, we fabricated hyaluronidase-sensitive multilayers of chitosan (Chi)/sodium hyaluronate-lauric acid (SL) onto the surface of bone morphogenetic protein 2 (BMP2) loaded titanium nanotube (TNT) via spin-assisted layer-by-layer technique. The results of both Fourier transform infrared spectroscopy (FTIR) and nuclear magnetic resonance ( 1 H NMR) confirmed the successful synthesis of SL. The multilayer structure on BMP2 loaded TNT was characterized by field-emission scanning electron microscopy (FE-SEM), atomic force microscopy (AFM) and water contact angle, respectively. The release profiles confirmed that hyaluronidase could trigger the release of lauric acid (LA) from the SL multilayer and accelerate the release of BMP2 in the system. The hyaluronidase-sensitive-multilayer-coated BMP2-loaded TNT (TNT/BMP2/(Chi/SL/Chi/Gel) 4 ) not only demonstrated good antibacterial capability, but also showed good biocompatibility in in vitro usage, which was supported by the efficient growth inhibition of both Staphylococcus aureus and Escherichia coli , as well as higher cell viability, alkaline phosphatase activity, mineralization capability, and higher gene expression of osteoblasts on TNT/BMP2/(Chi/SL/Chi/Gel) 4 . This study developed an alternative approach to fabricate effective antibacterial implants for orthopedic implantation.
研究领域:
材料科学
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生物材料
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骨科
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生物医学工程
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药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）