American Journal of Translational Research
·
2019
·
IF 3.266
Zhao Wang,Hong-Wei Bao
Our aim was to study the osteogenic effect of cnidium lactone for bone marrow mesenchymal stem cells (BMSCs) and its potential mechanism. BMSCs were isolated and identified by flow cytometry and multidirectional differentiation capacity. Cell Counting Kit-8 (CCK-8) was used to identify the optimal concentration of cnidium lactone. Alkaline Phosphatase (ALP) and Alizarin Red S (ARS) was performed to identify whether cnidium lactone has effect on osteogenesis at early and late phase respectively. Moreover, we used estrogen receptor antagonist, ICI182780, to identify the receptor of cnidium lactone. The expression of Runt-related transcription factor 2 (RUNX2), Osterix (OSX), osteopontin (OPN), estrogen receptor (ER), Smad4, p-Smad1, Smad1 and bone morphogenetic protein 2 (BMP-2) protein were measured by PCR and western blot. Cnidium lactone (2 μM) demonstrated increased osteogenesis after osteogenic inducible medium (OIM) induction, as evidenced by more ALP activity and mineralization. When blocked with ICI182780, osteogenesis capacity was decreased. Moreover, the polymerase chain reaction (PCR) and western blotting results indicated that cnidium lactone enhanced ER, BMP2, Smad1, Smad4, RUNX2, OSX, and OPN expression and Smad1 phosphorylation. Cnidium lactone can effectively stimulates osteogenic differentiation of BMSCs via BMP-2/Smad-Signaling cascades mediated by ER.
研究领域:
药理学
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干细胞生物学
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骨骼再生
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DOI
PubMed
高影响因子
JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS
·
2022
·Vol. 110
·期 9
·2075-2088
·
IF 3.405
Shuang Qin,Zhengkuan Lu,Kang Gan,Chunyan Qiao,Baosheng Li,Tianjie Chen,Yunbo Gao,Lingling Jiang,Hong Liu
Polyetheretherketone (PEEK) has been widely investigated for improving its biological inert to enable it to achieve stronger osteogenic capability and to be a promising material in implant fields. The most important mechanism that makes a successful implantation is osteointegration. Surface modification is an appropriate method to maintain the excellent mechanical properties of PEEK and simultaneously endow PEEK certain biological characters. In this work, we attempted to shape the nano-topography of PEEK surface by nitrogen low-temperature plasma and polydopamine coating on the surface as a secondary reaction platform to bond the aminated poly (lactic-co-glycolic acid) (PLGA) microspheres encapsulating the BMP-2 gene for enhancing the biological activity. Scanning electron microscope, atomic force microscopy, X-ray photoelectron spectroscopy and water contact angle (CA) measurements were applied to characterize the surface of modified or untreated PEEK. Surface characterization showed that the modification was successfully performed on PEEK including a rougher and more hydrophilic surface with nanotopographic features. The influence on cell adhesion, proliferation and differentiation was evaluated by culturing of rat bone marrow mesenchymal stem cells on different modified PEEK substrates in vitro. The biological results indicated that the low-temperature plasma treatment and PDA-coating on PEEK significantly promoted cell adhesion and proliferation. And the osteogenic differentiation was effectively improved by BMP-2 gene releasing from PLGA-NH 2 microspheres. The results showed that this novel biological surface modification endowed PEEK with outstanding bioactivity and osteogenic ability, providing a theoretical basis for application in the field of implantation.
研究领域:
生物材料
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组织工程
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骨科
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生物医学工程
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DOI
PubMed
高影响因子
Frontiers in Bioengineering and Biotechnology
·
2026
·
IF 5.8
Yuan Fan,Haiyan Yao,Junchao Wei,Yipeng Hu
Titanium (Ti) implants are widely used in bone defect repair, however, postoperative infections and insufficient osseointegration would lead to implant failure. Therefore, it is much critical and necessary to construct antibacterial and osteogenic coatings on the surface of Ti implants to improve the successful rate of operation. Herein, D-penicillamine stabilized chiral ZnO nanoparticles (D-ZnO NPs) were prepared, which were loaded on the surface of Ti implants together with BMP-2 to construct a dual functional coating with antibacterial and osteogenic properties. The in vitro results demonstrated that the coating showed excellent antibacterial ability, and the antibacterial rates against S. mutans , E. coli and S. aureus were 86%, 98%, and 76%, respectively. Additionally, the coating could effectively induce macrophage polarization towards M2 phenotype, which modulated the local immune microenvironment. Furthermore, the introduction of bone morphogenetic protein-2 (BMP-2) promoted osteogenesis, which may enhance the osseointegration of Ti implants. This study provides a novel strategy to address the challenges of Ti implants, and offer the solid theoretical foundation for expanding the clinical applications of multifunctional Ti implants materials.
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DOI
PubMed
高影响因子
Doklady Biochemistry and Biophysics
·
2021
·Vol. 497
·期 1
·123-129
·
IF 0.788
Zhao Liang,Luo Yuming,Wang Yijun,Zhao Fujian,Chen Xiaofeng,Cai Daozhang
Abstract This study aimed to evaluate if the 3D printed bioactive glass porous scaffolds (BGS) can improve the reconstruction of the large bone defect. A rabbit model of large bone defects was established by making a 1.0 or 1.5 cm segmental defect in the middle of the femur bone. Then a 1.0 or 1.5 cm BGS was implanted into the bone defect. X-ray imaging showed that in both 1.0 and 1.5 cm groups, the newly formed bone tissue could be observed at 4 weeks after implantation, but a strengthened ossification trend could be observed at different time points. In the 1.0 cm group, a larger number of newly formed bone tissues were observed at 4 weeks, and in the 1.5 group, more newly formed bone tissues were found at 8 weeks. Nevertheless, ossified tissue generation on the BGS mainly completed at 12 weeks after implantation in both groups. The H&E staining revealed that the 3D BGS was easily degraded to form osteoid-like material in vivo , where the neo-ossification gradually occurred from the edge to the center. Immunohistochemical analysis showed that in the 1.0 group, protein expressions of three osteogenesis-related genes- BMP, collagen I and RUNX-2-all peaked at 8 weeks, and then gradually decreased at 12 and 18 weeks. In the 1.5 group, BMP and collagen I peaked at 18 weeks.
研究领域:
骨科
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组织工程
·
材料科学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Shang Wang,Huan Lei,Yu Mi,Pei Ma,Daidi Fan
In bone defects, infections lead to excessive inflammation, increased bacterial, and bone lysis, resulting in irregular wounds that hinder new bone regeneration. Injectable bioactive materials with adequate antimicrobial activity and strong osteogenic potential are urgently required to remedy irregular defects, eradicate bacteria, and facilitate the generation of new bone tissue. In this research, injectable dual-network composite hydrogels consisting of sulfated chitosan, oxidized hyaluronic acid, β-sodium glycerophosphate, and Cu Sr doped mesoporous bioactive glass loaded with bone morphogenetic protein (CuSrMBG BMP-2 ) were utilized for the first time to treat infectious bone defects. Initially, the hydrogel was injected into the wound at 37 °C with minimal invasion to establish a stable state and prevent hydrogel loss. Subsequently, sulfated chitosan eliminated bacteria at the wound site and facilitated cell proliferation with oxidized hyaluronic acid. Additionally, CuSrMBG BMP-2 strengthened antibacterial properties, regulated inflammatory reactions, promoted angiogenesis and osteogenic differentiation, addressing the deficiency in late-stage osteogenesis. Specifically, the injectable dual-network hydrogel based on chitosan and hyaluronic acid is minimally invasive, offering antibacterial, anti-inflammatory, pro-angiogenic, and bone regeneration properties. Therefore, this hydrogel with injectable dual network properties holds great promise for the treatment of bone infections in the future.
研究领域:
生物材料
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组织工程
·
骨科
·
生物医学工程
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产品关联
DOI
PubMed
高影响因子
Biomaterials Advances
·
2022
·
IF 0
Ting Dai,Jiayi Ma,Su Ni,Chun Liu,Yan Wang,Siyu Wu,Jun Liu,Yiping Weng,Dong Zhou,Ana Jimenez-Franco,Hongbin Zhao,Xiubo Zhao
Electrospun PCL scaffolds have been widely used for tissue engineering as they have shown great potential to mimic the structure of the natural extracellular matrix (ECM). However, the small pore size and low bioactivity of the scaffolds limit cell migration and tissue formation. In this study, PCL (polycaprolactone), PCL/PEG (polyethylene glycol), and PCL/PEG/ATP (nano-attapulgite) scaffolds were fabricated via electrospinning. To increase the porosity of the scaffolds, they were washed to remove water-soluble PEG fibers. Then the porous structure was measured using scanning electron microscopy (SEM) and atomic force microscopy (AFM), which showed an increased porosity when PEG fibers were removed in PCL/PEG and PCL/PEG/ATP scaffolds. Moreover, the mechanical properties were also analyzed in dry and wet conditions. In vitro mouse multipotent mesenchymal precursor cells were used to assess the biocompatibility of the scaffolds, and osteogenesis was analyzed using CCK-8 and real-time PCR (RT-PCR) methods. Moreover, in vivo μCT, histological and immunohistochemical analyses were conducted to evaluate new bone formation in rat cranium defect models. Washed PCL/PEG/ATP scaffolds were implanted into the cranium defects in rats for 4 or 8 weeks, better cell infiltration was observed in these scaffolds than in unwashed ones. The result demonstrated that washed PCL/PEG/ATP scaffold facilitated the differentiation of MSCs into osteoblasts compared with PCL scaffold, as proved by the increased expression of osteogenic key genes as well as Smad1, Smad4, and Smad5. Furthermore, in vivo studies demonstrated that using the ATP-doped electrospun PCL scaffold can improve the bone regeneration of rat cranium defects. Particularly, the PCL/ATP-30% scaffold has the best effect compared to the other scaffolds. The enhanced osteogenesis and bone repair were related to the PCL/ATP activated BMP/Smad signaling pathway.
研究领域:
组织工程
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材料科学
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生物医学工程
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产品关联
DOI
PubMed
Scientific Reports
·
2017
·Vol. 7
·期 1
·1-13
·
IF 4.259
Fu Chuan,Yang Xiaoyu,Tan Shulian,Song Liangsong
Lack of bioactivity has seriously restricted the development of biodegradable implants for bone tissue engineering. Therefore, surface modification of the composite is crucial to improve the osteointegration for bone regeneration. Bone morphogenetic protein-2 (BMP-2), a key factor in inducing osteogenesis and promoting bone regeneration, has been widely used in various clinical therapeutic trials. In this study, BMP-2 was successfully immobilized on graphene oxide-incorporated PLGA/HA (GO-PLGA/HA) biodegradable microcarriers. Our study demonstrated that the graphene oxide (GO) facilitated the simple and highly efficient immobilization of peptides on PLGA/HA microcarriers within 120 min. To further test in vitro , MC3T3-E1 cells were cultured on different microcarriers to observe various cellular activities. It was found that GO and HA significantly enhanced cell adhesion and proliferation. More importantly, the immobilization of BMP-2 onto the GO-PLGA/HA microcarriers resulted in significantly greater osteogenic differentiation of cells in vitro , as indicated by the alkaline phosphate activity test, quantitative real-time polymerase chain reaction analysis, immunofluorescence staining and mineralization on the deposited substrates. Findings from this study revealed that the method to use GO-PLGA/HA microcarriers for immobilizing BMP-2 has a great potential for the enhancement of the osseointegration of bone implants.
研究领域:
生物医学工程
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组织工程
·
骨再生
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材料科学
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DOI
PubMed
高影响因子
American Journal of Translational Research
·
2018
·
IF 3.061
Qian Tang,Minji Tong,Gang Zheng,Liyan Shen,Ping Shang,Haixiao Liu
The Masquelet’s induced membrane (IM) technique is widely used to treat large segmental bone defects due to its physical priority and biological function. However, the underlying molecular mechanism of the IM on bone formation remains unknown. In the present study, rat bone marrow-derived mesenchymal stem cells (BMSCs) were used as an in vitro model and bone morphogenetic protein 2 (BMP-2) was used as a positive control to evaluate the effects of the IM on the osteogenic differentiation of BMSCs. Although the IM group did not exhibit a significant increase in the expression of Runt-related transcription factor 2 (Runx2), Collagen I (Col I), osteocalcin (OCN) and alkaline phosphatase (ALP) relative to the BMP-2 administration, the IM was considerably effective compared with the untreated group. Mechanistically, we found that the IM activated the Smad and mitogen-activated protein kinase (MAPK) pathways, which was further confirmed by application of specific inhibitors of Smad1/5/8 (LDN-193189) and ERK1/2 (U0126). After the combined treatment of the IM and LDN-193189 as well as U0126, the IM-induced increase in Runx2, Col I, and OCN expression was significantly inhibited. These results suggest that IM promotes the osteogenic differentiation of rat BMSCs by activating the Smad1/5/8 and MAPK pathways.
研究领域:
骨科
·
干细胞生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Clinical Oral Investigations
·
2026
·Vol. 30
·期 5
·213
·
IF 3.6
Yang Zhenyu,Yang Mengyao,Ye Jiaxue,Lei Xiaoyue,Huo Xiaodan,Qin Zirui,Qi Linlong,Chen Yiduo,Wang Yuan,Deng Shuli
Objectives Pulp necrosis in immature permanent teeth arrests root development and compromises long-term prognosis. This study aimed to develop a multifunctional scaffold integrating structural biomimicry, mechanical matching, and sustained growth factor release for orderly root regeneration. Materials and methods A poly(ε-caprolactone) (PCL) conical scaffold was fabricated via melt electrowriting (MEW) combined with mechanical winding. Bone morphogenetic protein‑2 (BMP‑2)-loaded microspheres were prepared and physically incorporated into the scaffold. The scaffold surface was modified with collagen. Human dental pulp stem cells (hDPSCs) were cultured on the scaffold to evaluate proliferation, adhesion, and osteogenic differentiation. Results The scaffold exhibited a trilayer “collagen–microsphere–PCL” architecture with mechanical compatibility (elastic modulus: 22.5 MPa; fracture strength: 5.29 MPa; elongation: 441.59%). Microspheres (2.86 ± 0.45 μm) showed a gradient distribution and sustained release (70–75% over 90 days). In vitro, the scaffold promoted hDPSC adhesion and proliferation and significantly enhanced osteogenic differentiation with elevated alkaline phosphatase activity, upregulated the expression of osteogenic-related genes, and increased protein levels. Conclusions The scaffold integrates structural support, controlled growth factor delivery, and a bioactive interface, offering a promising strategy for root development in immature permanent teeth. Clinical relevance By enabling physiological root development, the scaffold addresses a critical unmet need, offering a viable alternative to conventional root canal therapy.
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DOI
PubMed
高影响因子
JOURNAL OF APPLIED POLYMER SCIENCE
·
2024
·
IF 2.7
Zhenxu Wu,Guoqing Niu,Zongtai Xiong,Xinxiang Ding,Yongbo Li,Peibiao Zhang,Feng Wu
Deer bone in traditional Chinese medicine is valued for its unique biomimetic bone matrix components. Icariin (Ica), which is claimed by Chinese medicine as a bone-repairing agent, is also widely accepted. In this report, a novel Ica-encapsulated PLGA/nano deer bone meal (Ica@PLGA/nBM) biomimetic microsphere was fabricated. The Ica could be released from microspheres in a controlled manner. In vitro results showed that the microsphere had good biocompatibility due to the addition of nBM and the MC3T3-E1 cells could adhere to and grow well on the microspheres. Moreover, Ica and nBM in microspheres could synergically promote the ALP activity of MC3T3-E1 cells significantly ( p < 0.05), which indicated the acceleration of osteogenic differentiation. The RT-PCR results showed that the expression levels of bone matrix proteins (Col1 & OPN) were enhanced by the composite ( p < 0.05). In addition, Ica and nBM in microspheres also obviously promoted the expression of RUNX2 and BMP-2, respectively ( p < 0.05). The in vivo results demonstrated the effective promotion of Ica@PLGA/nBM on complete bony connection to cover the defect site and the bone defect repair. And the Ica(M)@PLGA/nBM microspheres provided the best repair results. All the results confirmed that the Ica@PLGA/nBM composite biomimetic microsphere has the potential for clinical application.
研究领域:
材料科学
·
生物医学工程
·
药理学
·
组织工程
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DOI
高影响因子
PHYTOMEDICINE
·
2023
·
IF 7.9
Jun Jiang,Baixiu Zhao,Jianpeng Xiao,Liang Shi,Wei Shang,Ye Shu,Zhiming Zhao,Junyi Shen,Jingjuan Xu,Hui Cai
Background Clinical studies indicated that postmenopausal osteoporosis (PMOP) often accompanied by iron overload risk factor, which exacerbated bone metabolism disorders and accelerated PMOP. Previous research found that multicomponent in Ligustri Lucidi Fructus (FLL) or wine-steamed FLL (WFLL) acted on the common targets of iron overload and PMOP simultaneously, which indicated that FLL and WFLL probably regulated iron/bone metabolism dually. Additionally, WFLL had more superior effect according to the theory of Chinese medicine for thousands of years. Purpose To reveal the “superior multi-component structure (SMCS)” and its molecular mechanisms in parallelly down-regulating iron overload and rescuing bone metabolism by WFLL. Designs and methods HPLC fingerprinting was established to compare the chemical profiles of FLL and WFLL; Then, the chemical compositions and quality markers of FLL and WFLL were analyzed by UPLC-Orbitrap-MS/MS coupled with OPLS-DA; The dynamic contents of quality markers and the multi-component structure at different wine steaming times (WST) were simultaneously determined by HPLC-DAD; Meanwhile, the dynamic efficacy of FLL at different WST were hunt by systematic zebrafish model. Subsequently, potential mechanism of WFLL in treating PMOP accompanied with iron overload was obtained from network pharmacology (NP) and molecular docking (MD). Finally, zebrafish and ovariectomy rat model were carried out to validate this potential mechanism. Results HPLC fingerprints similarity of 15 batches in FLL and WFLL were among 0.9-1.0. 126 compositions were identified, including 58 iridoids, 25 terpenes, 30 phenylethanoids, 7 flavonoids and 6 others. 20 quality markers associated with WFLL was revealed, and the ratio of Phenylethanols: Iridoids: Triterpenes (P/I/T) was converted from 1: 15: 4.5 to 1: 0.8: 0.9 during steaming (0 - 24 h) calculated by the quantification of 11 quality markers; The bone mineralization and motor performance of zebrafish larvae indicated that the optimum efficacy of WFLL at 12 h ( P < 0.05) in which the SMCS of P/I/T was converted to 1: 4: 1.8. NP discovered that BMP-Smad pathway is one of the potential mechanisms of FLL in anti PMOP and then regulated bone formation and iron overload simultaneously. MD revealed that 17 active ingredients and 10 core targets genes could spontaneously bind with appropriate affinity. Rats model verified that FLL and WFLL significantly reversed PMOP, based on the improvement in bone formation indexes (ALP, OPG, OGN), iron metabolism indicators (hepcidin, ferritin), bone microstructure (BMD, BV/TV, Tb. Th, Tb. N); Moreover, WFLL significant enhanced reversal effect in anti-PMOP compared to FLL ( P < 0.05). FLL and WFLL increased genes and proteins expression (Hep, BMP-6, p-Smad1/5, Smad4) related to BMP-Smad pathway compared with model group, and WFLL was more superior than FLL ( P < 0.05). Conclusion The SMCS of FLL was optimized by wine-steam, WFLL represented a dual effect in downregulating iron overload and promoting bone formation, and the BMP-Smad pathway is one of the potential molecular mechanisms.
研究领域:
药理学
·
中药学
·
骨代谢
·
铁代谢
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网络药理学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2021
·
IF 6.953
Bo Wang,Shuai Yuan,Wei Xin,Yi Chen,Qiwei Fu,Lexiang Li,Yang Jiao
Bone defect repair and tissue engineering is specifically challenging process because of the distinctive morphological and structural behaviours of natural bone with complex healing and biochemical mechanisms . In the present investigation, we designed dopamine adhesive chemistry-based fabrication of silk fibroin hydrogel (SFD) with incorporation of nano-hydroxyapatite (nHA)-graphene oxide (GO) hybrid nanofillers with well-arranged porous morphology immobilized with bone morphogenic protein-2 (BMP-2) for the effective in vitro rabbit bone marrow derived mesenchymal stem cells loading compatibility and in vivo new bone regrowth and collagen deposition ability. We have achieved bone-specific hydrogel scaffolds with upgraded structural features, mechanical properties and particularly promoted in vitro osteogenic differentiation and compatibility of rabbit bone marrow mesenchymal stem cells (rBMSCs). Structural and microscopic analyses established greater distributions of components and well-ordered and aligned porous structure of the hydrogel network. In vivo result of new bone regrowth was promisingly higher in the Bm@nHG-SFD hydrogel (85%) group as compared to the other treatment groups of nHG-SFD (77%) and nH-SFD (64%) hydrogel. Overall, we summarized that morphologically improved hydrogel material with immobilization of BMP-2 could be have more attentions for new generation bone regeneration therapies.
研究领域:
生物材料学
·
组织工程学
·
再生医学
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DOI
高影响因子
危险品化学品经营许可证（带存储）