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BMP/SMAD信号通路
ACS Biomaterials Science & Engineering · 2025 · IF 5.5

Microarc Oxidation Coatings Doped with a Low Proportion of Yttrium Enhance the Osseointegration of Titanium Implants through the BMP/Smad Pathway

Chenyang Zhang,Chenghui Qian,Guang Yang,Yiying Zhu,Binbin Kang,Xiaohong Chen,Si Chen

Adding metal ions is a promising strategy to enhance the biological performance of titanium implants. In this study, we aimed to explore the effects of yttrium on the osseointegration of titanium implants. First, a series of yttrium-doped titanium surfaces were fabricated via microarc oxidation (MAO) by incorporating yttrium acetate into the electrolyte, and then the surface characteristics of different substrates were evaluated. Subsequently, the cellular behaviors of different coatings were assessed, and the osteointegration effects were examined using a rat model. Finally, high-throughput sequencing was employed to elucidate the underlying mechanisms of the yttrium-doped MAO coatings. As the results indicated, the proportion of yttrium in the coatings increased as the concentration of yttrium acetate improved. Surface characterization revealed that the yttrium-doped MAO coatings exhibited a homogeneous porous morphology, with comparable roughness and wettability to those of the undoped MAO coating, while the morphology became inconsistent when the yttrium acetate concentration reached 30 mM. The in vitro assays demonstrated that the addition of yttrium notably improved the cell adhesion, spreading, proliferation, and osteogenic differentiation of MAO coatings when doped with a low proportion, accompanied by enhanced osseointegration according to the in vivo experiments. Further exploration revealed a significant enrichment of osseointegration-related signaling factors and the activation of BMP/Smad signaling in the effects of yttrium-doped titanium coatings, which was attributed to the excessive accumulation of phosphorylated Smad1/5/9 in the nucleus. In summary, our work demonstrates that the use of MAO coatings doped with a low proportion of yttrium can enhance the osseointegration of titanium implants, providing an efficient strategy to optimize titanium implant performance.

研究领域: 生物材料学 · 组织工程学 · 医学
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Biomaterials Advances · 2022 · IF 0

Attapulgite-doped electrospun PCL scaffolds for enhanced bone regeneration in rat cranium defects

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.

CAS / MDL: 518-47-8 81-88-9
研究领域: 组织工程 · 材料科学 · 生物医学工程
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CHEMICAL ENGINEERING JOURNAL · 2024 · IF 13.3

An intelligent controlled release hydrogel with photothermal effect for the treatment of bone defects

Hewei Wei,Ting Zhao,Xinglong Liu,Qiteng Ding,Shuai Zhang,Jiali Yang,Ning Wang,Lifeng Zhang,Guodong Chai,Guofeng Xia,Anning Li,Chuanbo Ding,Wencong Liu

To solve the difficulty of natural healing in patients with severe bone defects, and the challenges of insufficient autologous bone graft material and large incisions in conventional surgery, we were designed an intelligent co-regulated hydrogel system with NIR response. The goal is to be able to prevent inflammation and bacterial adhesion, thereby promoting repair and development of the bone defect area. The hydrogel system consisted of hyaluronic acid, carboxymethyl chitosan and Pht-loaded PDA-encapsulated ZIF-8 NPs (Pht@ZIF-8@PDA) by Schiff base reaction. Compared to high-temperature photothermal therapy (PTT), which destroyed surrounding healthy cells, the present study was based on a new strategy of mild photothermal therapy (42.5 ± 1.2 °C) and leaded to a better promotion of osteogenesis. NIR activated the photothermal properties of PDA in scaffolds, intelligently released Pht and Zn 2+ , inhibited Escherichia coli and Staphylococcus aureus (inhibition rate ≥ 96 %), and promoted bone regeneration in the rat model. Meanwhile, it could promote bone regeneration by upregulating osteogenic factors and stimulating the expression of proteins related to BMP/SMAD signaling pathway. The research highlights the potential applications of synergistically modulated hydrogels, which opens up a new application path for this material in bone tissue engineering, regenerative medicine, and other related fields.

CAS / MDL: 9004-61-9
研究领域: 生物医学工程 · 组织工程 · 再生医学 · 材料科学 · 药学
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Bioactive Materials · 2022 · IF 16.874

Graphene oxide/gallium nanoderivative as a multifunctional modulator of osteoblastogenesis and osteoclastogenesis for the synergistic therapy of implant-related bone infection

Ying Yang,Min Li,Bixia Zhou,Xulei Jiang,Dou Zhang,Hang Luo

Currently, implant-associated bacterial infections account for most hospital-acquired infections in patients suffering from bone fractures or defects. Poor osseointegration and aggravated osteolysis remain great challenges for the success of implants in infectious scenarios. Consequently, developing an effective surface modification strategy for implants is urgently needed. Here, a novel nanoplatform (GO/Ga) consisting of graphene oxide (GO) and gallium nanoparticles (GaNPs) was reported, followed by investigations of its in vitro antibacterial activity and potential bacterium inactivation mechanisms, cytocompatibility and regulatory actions on osteoblastogenesis and osteoclastogenesis. In addition, the possible molecular mechanisms underlying the regulatory effects of GO/Ga nanocomposites on osteoblast differentiation and osteoclast formation were clarified. Moreover, an in vivo infectious microenvironment was established in a rat model of implant-related femoral osteomyelitis to determine the therapeutic efficacy and biosafety of GO/Ga nanocomposites. Our results indicate that GO/Ga nanocomposites with excellent antibacterial potency have evident osteogenic potential and inhibitory effects on osteoclast differentiation by modulating the BMP/Smad, MAPK and NF-κB signaling pathways. The in vivo experiments revealed that the administration of GO/Ga nanocomposites significantly inhibited bone infections, reduced osteolysis, promoted osseointegration located in implant-bone interfaces, and resulted in satisfactory biocompatibility. In summary, this synergistic therapeutic system could accelerate the bone healing process in implant-associated infections and can significantly guide the future surface modification of implants used in bacteria-infected environments.

CAS / MDL: 107-21-1 7440-55-3
研究领域: 生物材料 · 组织工程 · 骨科 · 感染性疾病 · 纳米技术 · 生物医学工程
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2022 · IF 8.025

The osteogenesis and the biologic mechanism of thermo-responsive injectable hydrogel containing carboxymethyl chitosan/sodium alginate nanoparticles towards promoting osteal wound healing

Zewen Shi,Fang Yang,Qian Pang,Yiwei Hu,Haijian Wu,Xueqiang Yu,Xianjun Chen,Lin Shi,Bowen Wen,Rui Xu,Ruixia Hou,Dan Liu,Qingjiang Pang,Yabin Zhu

With the development of minimally invasive orthopedics, injectable materials for bone repair are attracted more attention, especially for those wound with a small external mouth and sizeable internal cavity. In this work, the hydrogel with features of thermo-responsiveness, degradability and injectability was designed and fabricated. The hydrogel, named as FHCS, is composed of Pluronic F-127 (F127) loaded with carboxymethyl chitosan/sodium alginate nanoparticles (nCS) and nanohydroxyapatite (nHA). The hydrogel FHCS was non-toxic and good hemocompatible. It can enhance the ALP activity and extracellular matrix calcification of MC3T3-E1 due to the chitosan-based nanoparticle components (nCS). Moreover, FHCS-5 (containing 5 mg/mL nCS) showed relative high expression of osteogenic genes and protein markers. Osteal regeneration was observed treated by FHCS-5 hydrogel in a critical-size rat calvarial bone defect model. CT scanning showed that the whole defect was basically covered by new bone after FHCS-5 hydrogel. The results of H&E staining and Masson's trichrome staining on histological sections further confirmed that FHCS-5 hydrogel promoted new osteal formation and maturation, which up regulated the osteogenic related genes and proteins of ALP, OCN, OPN through BMP/Smad signaling pathway. Hence, this study suggests that FHCS-5 hydrogels have a promising application for non-loading bone regeneration.

研究领域: 生物医学工程 · 材料科学 · 骨科 · 组织工程
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