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CHEMICAL ENGINEERING JOURNAL · 2024 · IF 13.3

Bisphosphonates activated keratin assembled nanoparticle targeting bone fracture for enhanced immunomodulatory and osteoinductivity

Jiaqi Zhong,Xiaodong Hu,Jieyang Dong,Yujiong Chen,Botao Liu,Mingming Hao,Haijiao Xie,Chunhai Ke,Zhaoxiang Peng

Bone fractures pose significant clinical challenges and require innovative solutions for effective treatment and rapid recovery. Nanoscale protein-based materials are prominent in biotechnology and biomedicine, demonstrating versatility in biological processes and drug delivery. Herein, we designed and fabricated self-assembled keratin nanoparticles via a bisphosphonate (BP)-activated conformation-conservative assembly process. We determined the structural properties of the nanoparticles and explored the immunomodulatory and osteoinductivity functions retained from keratin. In addition, the keratin-BP nanoparticles could repair bone fractures. This study on multifunctional self-assembled protein-drug nanoparticles provides useful baseline data for exploring novel therapeutic options for acute bone fracture and other diseases.

研究领域: 生物技术 · 生物医学 · 纳米技术 · 骨科
✓ 已验证 DOI 高影响因子
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Materials Express · 2020 ·Vol. 10 ·期 11 ·1795-1801 · IF 1.65

Bio-genic synthesis of ultra-small Au particles loaded silica nanoparticles for effective wound healing agent for the nursing care in the femoral fracture during surgery

Wang Hai-Yan,Wu Zhang-You

In this study, Au?SiO2 materials were synthesized by a simple biogenic approach using ultra-small Au nanoparticles (NPs) loaded on mesoporous SiO2 NPs. The functional groups, crystalline behavior, morphological structure, and elemental compositions of synthesized nanomaterials were characterized and confirmed by various techniques such as ultraviolet-visible (UV-Vis), X-ray diffraction (XRD) analysis, Fourier-transform infrared (FTIR) spectroscopy, transmission electron microscope (TEM) with energy dispersive X-ray (EDX) mapping, Zeta potential, and dynamic light scattering (DLS) analysis. The cell viability results also indicated that the nano Au NPs loaded on mesoporous SiO2 NPs exhibited highly efficient biocompatibility and low toxicity. The wound healing rate of mesoporous SiO2 and Au?SiO2 NPs were 82% and 96%, respectively, at the end of 14 days, which were higher than that of the control samples. These results strongly support the possibility of using these Au particles loaded on mesoporous SiO2 NPs as a promising wound healing agent for nursing care during femoral fracture surgery.

CAS / MDL: 1310-73-2
研究领域: 纳米医学 · 材料科学 · 生物工程
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JOURNAL OF PHARMACOLOGICAL SCIENCES · 2025 · IF 2.9

Sulfasalazine disrupts the interaction between TNFα and TNFR1 thus inhibiting NF-kB signaling activation to promote bone fracture healing

Jingwei Liu,Cheng Qiu,Xiaoxiong Wang,Ziqian Xiang,Junyuan Sun,Mingzheng Chang,Qingliang Ma,Yan Zhuang,Yunpeng Zhao,Qiang Yang,Lianlei Wang,Xinyu Liu

Fracture is a common type of traumas and alternative therapies to boost bone fracture healing is necessary. The aim of this study is to elucidate the role of sulfasalazine in bone fracture healing by using MC3T3-E1 cells in vitro and murine femoral fracture model in vivo . Western blotting, flow cytometry, RNA sequencing, Calcein AM/PI staining, Alizarin-Red-S staining, ALP activity assay, transmission electron microscope, histological staining, immunohistochemistry, immunofluorescence and Surface plasmon resonance analysis were performed in this study. Sulfasalazine failed to elicit ferroptosis in osteoblasts within acceptable dose manner while promoted osteogenic differentiation. Furthermore, sulfasalazine was identified to inhibit inflammation by declination of inflammatory biomarkers. Besides, TNFα was verified as a potential downstream target for sulfasalazine and the adverse effect of TNFα on osteogenic differentiation could be largely salvaged by sulfasalazine due to direct binding between these two molecules. RNA-seq further implied decreased transcription of genes related to NF-κB pathway. Murine study showed sulfasalazine promotes fracture healing as evidenced by increased bone remodeling both histologically and radiologically. Overall, sulfasalazine accelerates osteogenic differentiation and promotes bone healing by direct binding to and thus inhibiting TNFα, which subsequently suppresses NF-κB signaling. Therefore, sulfasalazine shows a promising outcome for the treatment of bone fracture.

CAS / MDL: 599-79-1
研究领域: 药理学 · 分子生物学 · 免疫学 · 骨科学 · 细胞生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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American Journal of Translational Research · 2021 · IF 4.06

LncRNA HAGLR absorbing miR-214-3p promotes BMP2 expression and improves tibial fractures

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.

CAS / MDL: 4463-44-9
研究领域: 分子生物学 · 骨科 · 再生医学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Bioactive Materials · 2023 · IF 18.9

Hematoma-like dynamic hydrogelation through natural glycopeptide molecular recognition for infected bone fracture repair

Shenghao Wang,Wenbo He,Huan Wang,Dachuan Liu,Miao Wang,Huilin Yang,Guoqing Pan,Bin Li

Infected bone fractures remain a major clinical challenge for orthopedic surgeons. From a tissue regeneration perspective, biomaterial scaffolds with antibacterial and osteoinductive activities are highly desired, while advanced materials capable of mimicking the pathological microenvironment during the healing process of infected tissues remain an area deserving more research. Hematoma, the gel-like blood coagulum, plays an essential role in bone fracture repair because of its ability to serve as a dynamic and temporary scaffold with cytokines for both pathogen elimination and tissue healing. In light of this, we designed a dynamic hydrogel with hematoma-like antimicrobial or reparative performance for infected bone fracture repair in this study. The proposed dynamic hydrogel network was based on the reversible recognition of a natural glycopeptide antibiotic vancomycin (Van) and its target dipeptide D-Ala-D-Ala (AA), which could serve as a hematoma-like scaffold for obliterating bacteria in the fracture region and promoting bone repair by introducing an endogenous osteogenic peptide (OGP). In vivo experiments demonstrated that the hydrogel could rapidly eradicate bacteria, improve bone regeneration and restore the local inflammatory microenvironment. Together, findings from this study imply that the use of hematoma-like dynamic hydrogel could lead to a biomimetic revolution in surgical strategies against susceptible bone fractures.

研究领域: 生物材料 · 组织工程 · 骨科 · 再生医学
✓ 已验证 DOI PubMed 高影响因子
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2025 · IF 8.5

Silk screws prepared by bidirectional dialysis for bone fracture fixation

Tong Guan,Yuanyuan Qian,Na Li,Yingchao Shen,Yang Gao,Feng Zhang

Resorbable devices for fracture fixation have gained extensive interest owing to their ability to avoid secondary surgery. Silk, as a biomaterial, is considered a promising candidate for fixation systems due to its biocompatibility, remarkable mechanical properties, and controllable degradation. However, the current methods for preparing silk fixation devices are complex and time-consuming, involving multiple processes, including dissolution, dialysis, lyophilization, etc. Here, we report a novel approach for fabricating silk fixation devices directly from a silk-LiBr solution through bidirectional dialysis. As the concentration of lithium bromide decreases and the ethanol concentration increases, the silk-LiBr solution undergoes a structural transition to β-sheet, resulting in hydrogel formation. The hydrogel is further processed into a robust silk fixation system through drying and machining. The obtained silk screw demonstrated a maximum compression modulus of 1.47 GPa. In vivo experiments demonstrated that the silk fixation system exhibits good biocompatibility and maintains fixation stability for up to 4 months. Notably, the silk-based screw retained 94.8 % of its weight after four months in rats. The significance of this study lies in the development of a fabrication technique that enables the direct processing of silk-LiBr solution into diverse material formats with tunable structures and properties.

研究领域: 生物材料 · 生物医学工程 · 骨科
✓ 已验证 DOI PubMed 高影响因子
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Animal Models and Experimental Medicine · 2024 · IF 3.8

Experimental study of a novel mouse model of tibial shaft fracture combined with blunt chest trauma

Bing Zhang,Tingting Fu,Yi Han,Gongke Li,Xianyao Wan,Yong Li

Backgroud Thoracic Trauma and Limb Fractures Are the Two most Common Injuries in Multiple Trauma. However, there Is Still a Lack of Mouse Models of Trauma Combining Tibial Shaft Fracture (TSF) and Thoracic Trauma. In this Study, we Attempted to Develop a Novel Mouse Model of TSF Combined with Blunt Chest Trauma (BCT). Methods A total of 84 C57BL/6J male mice were used as the multiple trauma model. BCT was induced by hitting the chests of mice with heavy objects, and TSF was induced by hitting the tibia of mice with heavy objects after intramedullary fixation. Serum specimens of mice were received by cardiac puncture at defined time points of 0, 6, 12, 24, 48, and 72 h. Results Body weight and body temperature tended to decrease within 24 h after multiple trauma. Hemoglobin analyses revealed a decrease during the first 24 h after multiple trauma. Some animals died by cardiac puncture immediately after chest trauma. These animals exhibited the most severe pulmonary contusion and hemorrhage. The level of lung damage varied in diverse mice but was apparent in all animals. Classic hematoxylin and eosin (H&E)-stained paraffin pulmonary sections of mice with multiple trauma displayed hemorrhage and an immunoinflammatory reaction. Bronchoalveolar lavage fluid (BALF) and serum samples of mice with multiple trauma showed an upregulation of interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-1 α (TNF-1 α ) compared with the control group. Microimaging confirmed the presence of a tibia fracture and pulmonary contusion. Conclusions The novel mouse multiple trauma model established in this study is a common trauma model that shows similar pathological mechanisms and imaging characteristics in patients with multiple injuries. This study is useful for determining whether blockade or intervention of the cytokine response is beneficial for the treatment of patients with multiple trauma. Further research is needed in the future.

研究领域: 创伤外科 · 免疫学 · 病理学
✓ 已验证 DOI PubMed 高影响因子
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ACS Nano · 2023 · IF 17.1

Bioinspired Mild Photothermal Effect-Reinforced Multifunctional Fiber Scaffolds Promote Bone Regeneration

Xiaodi Zhang,Qi Li,Longfei Li,Jiang Ouyang,Tong Wang,Junjie Chen,Xiaoqing Hu,Yingfang Ao,Duotian Qin,Liqun Zhang,Jiajia Xue,Jin Cheng,Wei Tao

Bone fractures are often companied with poor bone healing and high rates of infection. Early recruitment of mesenchymal stem cells (MSCs) is critical for initiating efficient bone repair, and mild thermal stimulation can accelerate the recovery of chronic diseases. Here, a bioinspired, staged photothermal effect-reinforced multifunctional scaffold was fabricated for bone repair. Uniaxially aligned electrospun polycaprolactone nanofibers were doped with black phosphorus nanosheets (BP NSs) to endow the scaffold with excellent near-infrared (NIR) responsive capability. Apt19S was then decorated on the surface of the scaffold to selectively recruit MSCs toward the injured site. Afterward, microparticles of phase change materials loaded with antibacterial drugs were also deposited on the surface of the scaffold, which could undergo a solid-to-liquid phase transition above 39 °C, triggering the release of payload to eliminate bacteria and prevent infection. Under NIR irradiation, photothermal-mediated up-regulation of heat shock proteins and accelerated biodegradation of BP NSs could promote the osteogenic differentiation of MSCs and biomineralization. Overall, this strategy shows the ability of bacteria elimination, MSCs recruitment, and bone regeneration promotion with the assistance of photothermal effect in vitro and in vivo, which emphasizes the design of a bioinspired scaffold and its potential for a mild photothermal effect in bone tissue engineering.

CAS / MDL: 98-10-2 75-09-2 75-89-8
研究领域: 组织工程 · 生物材料 · 生物医学工程 · 再生医学
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ACS Applied Nano Materials · 2022 · IF 6.14

Icaritin-Incorporated Porous Hollow Iron Oxide Nanostructures for Promoting Fracture Repair

Kaijia Zhang,Jian Dong,Jun Lu,Lan Li,Huan Liang,Jing Jin,Peng Wang,Xiaolian Sun,Qing Jiang

Bone fracture is a huge medical and sociological problem. Among various therapeutic drugs, icaritin (ICA), as a novel natural osteoinductive agent, has attracted considerable attention due to its remarkable osteogenic effect, but it still has some drawbacks such as poor bone targeting and a rapid plasma clearance rate. Recently, iron oxide nanoparticles (IONPs) show increasingly potential as drug delivery vehicles to overcome these limitations. In this study, porous hollow iron oxide nanoparticles (PHNPs) were synthesized via thermal decomposition and controllable oxidation methods and ICA was incorporated during the hydrophilic phase transfer process. The preosteoblastic MC3T3-E1 cell line was used to evaluate their osteogenic effect, and the results demonstrated that ICA-incorporated PHNPs displayed superior biocompatibility and pronounced alkaline phosphatase activity and expression of osteogenic-related genes and proteins in a synergistic manner. Mechanistic investigations demonstrated that the MEK/ERK/p90RSK signaling pathway might provide a potential explanation for ICA-incorporated PHNP-mediated osteogenic differentiation. Furthermore, hyaluronic acid–cholesterol (HA–CHOL) was used to establish nanoclusters (ICA-PHNP-NCs) for in vivo bone regeneration assessment using a murine femur fracture as a model. The results showed that ICA-PHNP-NCs efficiently accumulated at the fracture site in the presence of a static magnetic field and accelerated fracture repair rapidly and effectively. For the first time, the dual application of osteogenic agents transport and ICA delivery using the ICA-PHNP-NC formulation was achieved against bone fracture, providing a new treatment strategy for diseases related to fractures.

研究领域: 纳米技术 · 药学 · 骨科 · 生物材料
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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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ADVANCED FUNCTIONAL MATERIALS · 2025 · IF 19

Electric-Field-Assisted 3D Printing of Personalized Piezoelectric Implants for Non-Load-Bearing Bone Fracture Repair

Chang Liu,Chenxi Li,Yun Su,Yun Ke,Zichen Hao,Xiaochuan Geng,Shengfang Ge,Zhi Yang,Fan Yang,Jing Ruan

Non-load-bearing bone fractures remain a clinical challenge due to their limited self-healing ability. Conventional implant scaffolds lack personalized 3D structures and show limited osteoinductivity. Herein, an ultrasound-responsive piezoelectric scaffold with customized 3D structures is fabricated with an electric field–assisted 3D printing strategy. The prepared piezoelectric scaffold demonstrates an excellent piezoelectric coefficient with up to 3.5 pC N −1 and a natural bone-comparable compressive modulus of ≈125.3 MPa. Notably, the piezoelectric scaffold can promote the osteogenic differentiation of bone marrow mesenchymal stromal cells (BMSCs) by activating Voltage-Gated Calcium Channel (VGCC) related Ca 2+ /calmodulin (CaM) signaling pathways and enhancing intracellular calcium influx under low-intensity pulsed ultrasound (LIPUS) stimulation. In repairing rat cranial fractures, the piezoelectric scaffold exhibits significant healing efficacy. This study exploits an effective treatment approach for non-load-bearing bone fractures and lays the foundation for the repair of critical bone defects.

CAS / MDL: 64-17-5 68-12-2
研究领域: 生物医学工程 · 组织工程 · 再生医学 · 压电材料 · 3D打印技术
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CHEMICAL ENGINEERING JOURNAL · 2025 · IF 13.2

A multifunctional highly adhesive hydrogel mimicking snail mucus for hemostatic coating

Jingjing Yuan,Menghan He,Jueying Yang,Kang Li,Kexiang Fan,Hang Luo,Bo Li,Yu Chen

Femur fracture becomes increasingly common due to global population aging. Intramedullary nailing, a widely used treatment for fractures, tends to damage the blood vessels in the bone marrow cavity, which causes substantial hidden bleedings. The application of hydrogels to intramedullary nail hemostasis is limited by the challenges in balancing the adhesion, mechanical strength, and toughness. Inspired by the multi-network structure of snail mucus, which offers strong adhesion in harsh environments via adaptive wet-state contact followed by tight fitting upon dehydration, we developed a dual-network carboxymethyl chitosan (CMCS)-gluconic acid δ-lactone (GDL)-Ca 2+ /polyacrylamide (PAM) (CGC/P) hydrogel. The integration of GDL with CMCS introduces hydroxyl groups to enhance the adhesion of hydrogel and regulated system pH to facilitate the formation of the dynamic CMCS-GDL-Ca 2+ physical crosslinking network. The chemically crosslinked PAM network further improves the strength and toughness of the hydrogel. As the adhesion strength of the hydrogel can be increased by up to 50.14 times upon dehydration, a stretch-winding and dehydration method is developed to coat intramedullary nails with controllable thickness, effective hemostatic properties, excellent mechanical and adhesion characteristics. In rabbit femoral intramedullary nailing surgery, this system achieves rapid hemostasis and greatly promotes osteogenesis. Our study simultaneously improves the performance regulation contradiction of hydrogel coating, providing a crucial support to promote the application of hemostatic coatings to implantations.

CAS / MDL: 79-06-1 90-80-2
研究领域: 生物医学工程 · 材料科学 · 组织工程 · 骨科 · 生物材料
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