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CHEMICAL ENGINEERING JOURNAL · 2025 · IF 13.2

Ultrasound-responsive piezoelectric hydrogels accelerate bone defect repair by regulating mitochondrial OXPHOS via activating AKT/GSK3β/β-catenin signaling axis

Siyu Zhao,Yue Li,Lin Dai,Bo Cheng

The development of artificial biomaterials that simulate the extracellular matrix of bone tissue is a promising strategy for bone regeneration. Hydrogel has become a feasible alternative, yet its lack of biological activity still needs to be improved. Herein, a piezoelectric composite hydrogel (TBP) based on tripolyglycerol monostearate (TM) and loaded with barium titanate (BTO) nanoparticles through hydrogen bonding provided by polydopamine has been developed to promote osteogenesis. In vitro , TBP exhibits excellent injectability, shape adaptability and biodegradability, ensuring the feasibility of its biological applications. Moreover, by virtue of the piezoelectric conversion capability of BTO, TBP has the response ability to low-intensity pulsed ultrasound (LIPUS) and can generate local electrical signals. Meanwhile, TBP performs outstandingly in promoting the proliferation, migration, adhesion and osteogenic differentiation of MC-3 T3-E1 cells. More importantly, TBP combined with LIPUS stimulation can regulate mitochondrial oxidative phosphorylation (OXPHOS) through the AKT/GSK3β/β-catenin signaling cascade, thereby accelerating osteogenesis. In vivo , the application of TBP hydrogel to the bone defect site of rats, combined with LIPUS stimulation, shows satisfactory effects in promoting bone regeneration. To sum up, this piezoelectric composite hydrogel is expected to become a promising candidate for bone tissue engineering.

CAS / MDL: 56-81-5
研究领域: 生物材料 · 组织工程 · 生物医学工程 · 纳米技术 · 细胞生物学 · 再生医学
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RSC Advances · 2024 ·Vol. 14 ·期 31 ·22420-22433 · IF 3.9

Preparation and performance study of in situ mineralized bone tissue engineering scaffolds

Chunyan Tian,Kun Li,Fuhuan Chu,Qiujiang Wei,Shiqi Xu,Linhui Qiang,Xinrui Gou

Traditional bone tissue engineering techniques require the extraction and proliferation of seed cells, followed by prolonged in vitro culture to form bone tissue constructs. In contrast, in situ mineralization bone tissue engineering utilizes alkaline phosphatase within the body's microenvironment to induce scaffold mineralization. This approach promotes further proliferation and differentiation of osteoblasts and the formation of bone tissue constructs, thereby simplifying the traditional bone tissue engineering process. This study uses electrospinning technology to prepare a novel biologically active scaffold for bone tissue engineering using poly(lactic-co-glycolic acid) (PLGA) and calcium glycerophosphate. The morphology and composition of the scaffolds were characterized using SEM, EDS, and XRD, revealing well-defined fibrous structures and the successful incorporation of calcium glycerophosphate into the PLGA fibers. In vitro simulation of the bone microenvironment using alkaline phosphatase effectively catalyzed the in situ mineralization of calcium glycerophosphate within the scaffold. SEM observations showed substantial mineral aggregation on the surface of the fibrous membranes, and XRD characterization confirmed that the diffraction peaks of the minerals correspond to hydroxyapatite. The cytotoxicity, cell proliferation, and osteogenic differentiation assessments on MC3T3-E1 pre-osteoblasts cultured on the prepared scaffolds indicate that the scaffolds are non-toxic to cells and possess good osteogenic differentiation ability, enabling in situ mineralization. This suggests that the scaffolds have broad prospects for application in bone defect repair.

研究领域: 生物医学工程 · 材料科学 · 组织工程 · 细胞生物学
✓ 已验证 DOI PubMed 高影响因子
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JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION · 2018 · IF 1.911

Simvastatin delivery on PEEK for bioactivity and osteogenesis enhancements

Li-Jun Deng,Yan-Lin Wu,Xian-Hua He,Ke-Nan Xie,Lu Xie,Yi Deng

A strategy developed for obtaining positive cellular responses remains to be focused in the filed of functional biomimetics. In this study, a hydrogel covered simvastatin-loaded polyetheretherketone (PEEK) bio-composites was constructed with the purpose of bone tissue regeneration therapy. Briefly, a three-dimensional (3D) porous structure was fabricated on PEEK surface; then the substrate was functionalized with the poly(L-lactic acid)/simvastatin porous film and hyaluronic acid hydrogel subsequently. In vitro cell attachment, proliferation, and cytoskeletal observation experiments reveal that our scaffolds show better bio-affinity due to the layer of hyaluronic acid hydrogel compared with control. Furthermore, the alkaline phosphatase activity, calcium mineral deposition evaluation, and gene expression for osteogenic potential all exhibit that the superior osteogenic differentiation of MC3T3-E1 pre-osteoblasts on our scaffolds. Therefore, our PEEK samples loaded with simvastatin and covered with hyaluronic acid hydrogel hold great potential in clinical applications for bone repair.

CAS / MDL: 9067-32-7 79902-63-9
研究领域: 生物材料 · 组织工程 · 生物医学工程 · 细胞生物学
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JOURNAL OF CELLULAR PHYSIOLOGY · 2024 · IF 4.5

MAGP2 promotes osteogenic differentiation during fracture healing through its crosstalk with the β-catenin pathway

Zhiguang Chen,Qi Zhao,Lianghong Chen,Songlan Gao,Lingshuai Meng,Yingjie Liu,Yu Wang,Tiegang Li,Jinqi Xue

Osteogenic differentiation is important for fracture healing. Microfibrial-associated glycoprotein 2 (MAGP2) is found to function as a proangiogenic regulator in bone formation; however, its role in osteogenic differentiation during bone repair is not clear. Here, a mouse model of critical-sized femur fracture was constructed, and the adenovirus expressing MAGP2 was delivered into the fracture site. Mice with MAGP2 overexpression exhibited increased bone mineral density and bone volume fraction (BV/TV) at Day 14 postfracture. Within 7 days postfracture, overexpression of MAGP2 increased collagen I and II expression at the fracture callus, with increasing chondrogenesis. MAGP2 inhibited collagen II level but elevated collagen I by 14 days following fracture, accompanied by increased endochondral bone formation. In mouse osteoblast precursor MC3T3-E1 cells, MAGP2 treatment elevated the expression of osteoblastic factors (osterix, BGLAP and collagen I) and enhanced ALP activity and mineralization through activating β-catenin signaling after osteogenic induction. Besides, MAGP2 could interact with lipoprotein receptor-related protein 5 (LRP5) and upregulated its expression. Promotion of osteogenic differentiation and β-catenin activation mediated by MAGP2 was partially reversed by LRP5 knockdown. Interestingly, β-catenin/transcription factor 4 (TCF4) increased MAGP2 expression probably by binding to MAGP2 promoter. These findings suggest that MAGP2 may interact with β-catenin/TCF4 to enhance β-catenin/TCF4's function and activate LRP5-activated β-catenin signaling pathway, thus promoting osteogenic differentiation for fracture repair. mRNA sequencing identified the potential targets of MAGP2, providing novel insights into MAGP2 function and the directions for future research.

研究领域: 骨骼生物学 · 骨科 · 分子生物学 · 细胞生物学
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BIOMEDICINE & PHARMACOTHERAPY · 2024 · IF 6.9

The bone-protective benefits of kaempferol combined with metformin by regulation of osteogenesis-angiogenesis coupling in OVX rats

Zhongyuan Zhang,Wenshu Xu,Zhenhua Zhang,Xiaoxue Chen,Hui Jin,Ningning Jiang,Hui Xu

This study was to investigate the potential mechanisms of treatment with metformin (Met) combined with kaempferol (Kae) against postmenopausal osteoporosis. Experiments were conducted in both ovariectomy (OVX)-induced osteoporosis rats and in vitro using RAW264.7 cells, MC3T3-E1 cells, and HUVECs. Results demonstrated the therapeutic effect of Met combined with Kae on osteoporosis. In vivo, Kae alone and in combination with Met treatments enhanced tibial trabecular microstructure, bone mineral density (BMD), and mechanical properties in OVX rats without causing hepatotoxicity and nephrotoxicity. It also reduced bone resorption markers (CTX-1 and TRAP) and increased the bone formation marker (PINP) level in the serum of OVX rats. The expression of bone resorption marker TRAP was reduced, while bone formation markers Runx2 and ALP were enhanced in the bone tissue of OVX rats. Furthermore, Met combined with Kae also promoted the expression of angiogenesis-related markers CD31 and VEGF in OVX rats. In vitro, MC3T3-E1s cells treated with Met combined with Kae showed higher expression of ALP, Runx2, and VEGF. Interestingly, the treatment did not directly promote HUVECs migration and angiogenesis, but enhanced osteoblast-mediated angiogenesis by upregulating VEGF levels. Additionally, Met combined with Kae treatment promoted VEGF secretion in MC3T3-E1, and activated the Notch intracelluar pathway by upregulating HES1 and HEY1 in HUVECs. Meantime, their stimulation on CD31 expression were inhibited by DAPT, a Notch signaling inhibitor. Overall, this study demonstrates the positive effects of Met combined with Kae on osteoporotic rats by promoting osteogenesis-angiogenesis coupling, suggesting their potential application in postmenopausal osteoporosis.

研究领域: 药理学 · 骨科 · 分子生物学 · 细胞生物学
✓ 已验证 DOI PubMed 高影响因子
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CELL BIOLOGY INTERNATIONAL · 2019 ·Vol. 44 ·期 2 ·402-411 · IF 2.127

Melatonin promotes osteoblastic differentiation and regulates PDGF/AKT signaling pathway

Guiling Zhu,Bin Ma,Penghong Dong,Junjun Shang,Xiaochuan Gu,Ying Zi

Melatonin has been reported to participate in bone metabolism in recent studies. However, the underlying mechanism in melatonin-mediated osteoblastic differentiation remains largely unknown. The aim of this study is to investigate the role of melatonin in osteoblastic differentiation. In the present study, additional melatonin significantly promoted osteoblastic differentiation of MC3T3-E1 cells as evidenced by increased messenger RNA (mRNA) levels of osteogenic markers, alkaline phosphatase (ALP), collagen type I α1 chain, osteocalcin, and runt-related transcription factor 2 (Runx2). It was noteworthy that the expression level of platelet-derived growth factor subunit B (PDGFB) and content of its homodimer PDGF-BB were remarkably increased after melatonin administration. Moreover, the mRNA levels of phosphorylated PDGFRβ (PDGF receptor β) and Akt, a serine/threonine-specific protein kinase, were significantly upregulated in melatonin-treated MC3T3-E1 cells determined by a real-time polymerase chain reaction. Besides, by performing alizarin red staining, osteoblastic differentiation of MC3T3-E1 cells was conspicuously promoted by melatonin, which could be partially attenuated by crenolanib, a PDGFR inhibitor. Similarly, results from immunofluorescence and western blot assay showed that melatonin-induced upregulation of Runx2 and phosphorylated Akt was suppressed by crenolanib. Akt inhibition by MK-2206 also suppressed osteoblastic differentiation. Furthermore, by in vivo assay, additional melatonin promoted osteoblastic differentiation in mice with femoral fracture, and obvious callus formation was observed in melatonin-treated mice 5 weeks after fracture. Melatonin supplement also inhibited osteoclastic differentiation in mice. All statistical analysis was performed using GraphPad Prism and a P < 0.05 was deemed to be significant. To summarize, we demonstrate that melatonin promotes osteoblastic differentiation in MC3T3-E1 cells and enhances fracture healing in mouse femoral fracture model and regulates PDGF/AKT signaling pathway.

CAS / MDL: 50-81-7
研究领域: 骨骼生物学 · 药理学 · 细胞信号传导 · 分子生物学
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JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A · 2024 · IF 3.9

Fabrication of vascularized tissue-engineered bone models using triaxial bioprinting

Junbiao Zhang,Srisurang Suttapreyasri,Chidchanok Leethanakul,Bancha Samruajbenjakun

Bone tissue is a highly vascularized tissue. When constructing tissue-engineered bone models, both the osteogenic and angiogenic capabilities of the construct should be carefully considered. However, fabricating a vascularized tissue-engineered bone to promote vascular formation and bone generation, while simultaneously establishing nutrition channels to facilitate nutrient exchange within the constructs, remains a significant challenge. Triaxial bioprinting, which not only allows the independent encapsulation of different cell types while simultaneously forming nutrient channels, could potentially emerge as a strategy for fabricating vascularized tissue-engineered bone. Moreover, bioinks should also be applied in combination to promote both osteogenesis and angiogenesis. In this study, employing triaxial bioprinting, we used a blend bioink of gelatin methacryloyl (GelMA), sodium alginate (Alg), and different concentrations of nano beta-tricalcium phosphate (nano β-TCP) encapsulated MC3T3-E1 preosteoblasts as the outer layer, a mixed bioink of GelMA and Alg loaded with human umbilical vein endothelial cells (HUVEC) as the middle layer, and gelatin as a sacrificial material to form nutrient channels in the inner layer to fabricate vascularized bone constructs simulating the microenvironment for bone and vascular tissues. The results showed that the addition of nano β-TCP could adjust the mechanical, swelling, and degradation properties of the constructs. Biological assessments revealed the cell viability of constructs containing different concentrations of nano β-TCP was higher than 90% on day 7, The cell-laden constructs containing 3% (w/v) nano β-TCP exhibited better osteogenic (higher Alkaline phosphatase activity and larger Osteocalcin positive area) and angiogenic (the gradual increased CD31 positive area) potential. Therefore, using triaxial bioprinting technology and employing GelMA, Alg, and nano β-TCP as bioink components could fabricate vascularized bone tissue constructs, offering a novel strategy for vascularized bone tissue engineering.

研究领域: 组织工程 · 生物打印 · 生物材料 · 再生医学
✓ 已验证 DOI PubMed 高影响因子
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Materials Science & Engineering C-Materials for Biological Applications · 2020 · IF 5.88

Biomimetic organic-inorganic hybrid hydrogel electrospinning periosteum for accelerating bone regeneration

Wenjuan Liu,Wei Bi,Yang Sun,Lei Wang,Xiaohua Yu,Ruoyu Cheng,Youcheng Yu,Wenguo Cui

Periosteum as an important component in the construct of bone is mainly responsible for providing nourishment and regulating osteogenic differentiation. When bone defect happens, the functionality of periosteum will also be influenced, furthermore, it will finally hamper the process of bone regeneration. However, fabrication of an artificial periosteum with the capabilities in accelerating angiogenesis and osteogenesis in the defect area is still a challenge for researchers. In this study, we fabricated an organic-inorganic hybrid biomimetic periosteum by electrospinning, which can induce mineralization in situ and control the ions release for long-term in local area. Further, this system exhibited potential capabilities in promoting in vitro, which means the potentiality in accelerating bone regeneration in vivo. Calcium phosphate nanoparticles (CaPs) were fabricated by emulsion method, then CaPs were further incorporated with gelatin-methacryloyl (GelMA) by electrospinning fibers to construct the hybrid hydrogel fibers. The fibers exhibited satisfactory morphology and mechanical properties, additionally, controlled ions release could be observed for over 10 days. Further, significant mineralization was proved on the surface of hybrid fibers after 7 days and 14 days' co-incubation with simulated body fluid (SBF). Then, favorable biocompatibility of the hybrid fibers was approved by co-cultured with MC3T3-E1 cells. Finally, the hybrid fibers exhibited potential capabilities in promoting angiogenesis and osteogenesis by co-culture with HUVECs and MC3T3-E1 cells. This biomimetic organic-inorganic hybrid hydrogel electrospinning periosteum provided a promising strategy to develop periosteum biomaterials with angiogenesis and osteogenesis capabilities.

CAS / MDL: 760-93-0
研究领域: 材料科学 · 生物医学工程 · 组织工程 · 生物材料 · 再生医学
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JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS · 2019 ·Vol. 108 ·期 4 ·1505-1517 · IF 2.674

In vitro and in vivo assessment of glucose cross-linked gelatin/zein nanofibrous scaffolds for cranial bone defects regeneration

Lingli Deng,Yang Li,Hui Zhang

The purpose of this study was to evaluate the glucose cross-linked gelatin/zein scaffolds for bone regeneration in vitro and in vivo. The nanofibrous scaffolds exhibited fast mineralization in the concentrated simulated body fluid with the deposited octacalcium phosphate and dicalcium phosphate dehydrate. The nanofibrous scaffolds exhibited no cytotoxic effect on MC3T3e1 cells in a CCK-8 test. Additionally, scanning electron microscope and confocal laser scanning microscopy images revealed that all the scaffolds were biocompatible and showed excellent support for MC3T3e1 cells. In the osteogenesis characterizations, Alizarin Red staining experiments indicated the improved calcium deposits on the cross-linked scaffolds, while the alkaline phosphatase activity showed no difference. Furthermore, the in vivo cranial bone regeneration results suggested that the cross-linked gelatin/zein scaffolds presented a strong positive effect on the cranial bone regeneration with the increased new bone volume and connective tissue formation, but the incorporation of zein in the gelatin scaffolds did not favor the bone regeneration. Moreover, the cross-linked gelatin scaffold retarded the bone resorption as indicated by the higher levels of IFN-γ and lower levels of IL-6, which restricted the differentiation of osteoclasts.

CAS / MDL: 9000-70-8
研究领域: 生物材料 · 组织工程 · 再生医学
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Materials Today Bio · 2024 · IF 8.7

Dual-functional thermosensitive hydrogel for reducing infection and enhancing bone regeneration in infected bone defects

Yuhang Tian,Yutao Cui,Guangkai Ren,Yi Fan,Minghan Dou,Shaorong Li,Gan Wang,Yanbing Wang,Chuangang Peng,Dankai Wu

The contamination of bone defects is a serious therapeutic problem. The treatment of infected bone defects involves rigorous infection control followed by bone reconstruction. Considering these two processes, the development of biomaterials possessing antibacterial and osteogenic properties offers a promising approach for the treatment of infected bone defects. In this study, a dual-functional, thermosensitive, and injectable hydrogel composed of chitosan (CS), quaternized CS (QCS), and nano-hydroxyapatite (nHA) was designed, and the ratio of CS to QCS in the hydrogel was optimized to enhance the antibacterial efficacy of CS while reducing the cytotoxicity of QCS. In vitro studies demonstrated that the hydrogel with an 85 %:15 % ratio of CS to QCS exhibited excellent biocompatibility and antibacterial properties while also possessing suitable mechanical characteristics and degradability. The incorporation of nHA into the hydrogel enhanced MC3T3-E1 proliferation and osteogenic differentiation. Moreover, this hydrogel demonstrated superior in vivo therapeutic effectiveness in a rabbit model of infected bone defect. In summary, this study provides a promising material design and a comprehensive one-step treatment strategy for infected bone defects.

研究领域: 生物材料 · 组织工程 · 骨科 · 传染病 · 生物医学工程
✓ 已验证 DOI PubMed 高影响因子
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JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION · 2024 · IF 3.6

Enhanced osteogenesis and antibacterial activity of dual-functional PEEK implants via biomimetic polydopamine modification with chondroitin sulfate and levofloxacin

Mengjue Li,Junyan Liu,Yutong Li,Wenyu Chen,Zhou Yang,Yayu Zou,Yi Liu,Yue Lu,Jianfei Cao

Polyetheretherketone (PEEK) implants have emerged as a clinically favored alternative to titanium alloy implants for cranial bone substitutes due to their excellent mechanical properties and biocompatibility. However, the biological inertness of PEEK has hindered its clinical application. To address this issue, we developed a dual-functional surface modification method aimed at enhancing both osteogenesis and antibacterial activity, which was achieved through the sustained release of chondroitin sulfate (CS) and levofloxacin (LVFX) from a biomimetic polydopamine (PDA) coating on the PEEK surface. CS was introduced to promote cell adhesion and osteogenic differentiation. Meanwhile, incorporation of antibiotic LVFX was essential to prevent infections, which are a critical concern in bone defect repairing. To our delight, experiment results demonstrated that the SPKD/CS-LVFX specimen exhibited enhanced hydrophilicity and sustained drug release profiles. Furthermore, in vitro experiments showed that cell growth and adhesion, cell viability, and osteogenic differentiation of mouse calvaria-derived osteoblast precursor (MC3T3-E1) cells were significantly improved on the SPKD/CS-LVFX coating. Antibacterial assays also confirmed that the SPKD/CS-LVFX specimen effectively inhibited the growth of Escherichia coli and Staphylococcus aureus, attributable to the antibiotic LVFX released from the PDA coating. To sum up, this dual-functional PEEK implant showed a promising potential for clinical application in bone defects repairing, providing excellent osteogenic and antibacterial properties through a synergistic approach.

CAS / MDL: 62-31-7
研究领域: 生物材料 · 组织工程 · 骨科 · 生物医学工程 · 材料科学
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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY · 2024 · IF 5.7

Novel Peptides from Sturgeon Ovarian Protein Hydrolysates Prevent Oxidative Stress-Induced Dysfunction in Osteoblast Cells: Purification, Identification, and Characterization

Ruichang Gao,Lingling Zhu,Wei Zhang,Wengang Jin,Fan Bai,Peng Xu,Jinlin Wang,Quancai Sun,Zitao Guo,Li Yuan

This study aimed to explore antioxidant peptides derived from sturgeon (Acipenser schrenckii) ovaries that exhibit antiosteoporotic effects in oxidative-induced MC3T3-E1 cells. The F3–15 component obtained from sturgeon ovarian protein hydrolysates (SOPHs) via gel filtration and RP-HPLC significantly increased the cell survival rate (from 49.38 ± 2.88 to 76.26 ± 2.09%). Two putative antioxidant-acting peptides, FDWDRL (FL6) and FEGPPFKF (FF8), were screened from the F3–15 faction via liquid chromatography–tandem mass spectrometry (LC–MS/MS) and through prediction by computer simulations. Molecular docking results indicated that the possible antioxidant mechanisms of FL6 and FF8 involved blocking the active site of human myeloperoxidase (hMPO). The in vitro tests showed that FL6 and FF8 were equally adept at reducing intracellular ROS levels, increasing the activity of antioxidant enzymes, and protecting cells from oxidative injuries by inhibiting the mitogen-activated protein kinase (MAPK) pathway and activating the phosphoinositide-3 kinase (PI3K)/protein kinase B (AKT)/glycogen synthase kinase-3β (GSK-3β) signaling pathway. Moreover, both peptides could increase differentiation and mineralization abilities in oxidatively damaged MC3T3-E1 cells. Furthermore, FF8 exhibited high resistance to pepsin and trypsin, showcasing potential for practical applications.

研究领域: 生物化学 · 药理学 · 细胞生物学 · 分子生物学
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