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Bioactive Materials · 2020 · IF 8.724

Stepwise 3D-spatio-temporal magnesium cationic niche: Nanocomposite scaffold mediated microenvironment for modulating intramembranous ossification

Jie Shen,Bo Chen,Xinyun Zhai,Wei Qiao,Shuilin Wu,Xuanyong Liu,Ying Zhao,Changshun Ruan,Haobo Pan,Paul K. Chu,Kenneth M.C. Cheung,Kelvin W.K. Yeung

The fate of cells and subsequent bone regeneration is highly correlated with temporospatial coordination of chemical, biological, or physical cues within a local tissue microenvironment. Deeper understanding of how mammalian cells react to local tissue microenvironment is paramount important when designing next generation of biomaterials for tissue engineering. This study aims to investigate that the regulation of magnesium cationic (Mg 2+ ) tissue microenvironment is able to convince early-stage bone regeneration and its mechanism undergoes intramembranous ossification. It was discovered that moderate Mg 2+ content niche (~4.11 mM) led to superior bone regeneration, while Mg 2+ -free and strong Mg 2+ content (~16.44 mM) discouraged cell adhesion, proliferation and osteogenic differentiation, thereby bone formation was rarely found. When magnesium ions diffused into free Mg zone from concentrated zone in late time point, new bone formation on free Mg zone became significant through intramembranous ossification. This study successfully demonstrates that magnesium cationic microenvironment serves as an effective biochemical cue and is able to modulate the process of bony tissue regeneration. The knowledge of how a Mg 2+ cationic microenvironment intertwines with cells and subsequent bone formation gained from this study may provide a new insight to develop the next generation of tissue-repairing biomaterials.

CAS / MDL: 1309-48-4
研究领域: 组织工程 · 生物材料 · 再生医学
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Applied Materials Today · 2019 · IF 8.013

3D-printed nanocomposite scaffolds with tunable magnesium ionic microenvironment induce in situ bone tissue regeneration

Jie Shen,Wenhao Wang,Xinyun Zhai,Bo Chen,Wei Qiao,Wan Li,Penghui Li,Ying Zhao,Yuan Meng,Shi Qian,Xuanyong Liu,Paul K. Chu,Kelvin W.K. Yeung

Local tissue microenvironment is able to regulate cell-to-cell interaction that leads to effective tissue repair. This study aims to demonstrate a tunable magnesium ionic (Mg 2+ ) microenvironment in bony tissue that can significantly induce bone defect repair. The concept can be realized by using a newly fabricated nanocomposite comprising of custom-made copolymer polycaprolactone-co-poly(ethylene glycol)-co-polycaprolactone (PCL-PEG-PCL) and surface-modified magnesium oxide (MgO) nanoparticles. In this study, additive manufacturing (AM) technology had been adopted to help design the porous three-dimensional (3D) scaffolds with tunable Mg 2+ microenvironment. We found that the wettability and printability of new copolymer had been improved as compared with that of PCL polymer. Additionally, when MgO nanoparticles incorporated into the newly synthesized hydrophilic copolymer matrix, it could lead to increased compressive moduli significantly. In the in vitro studies, the fabricated nanocomposite scaffold with low concentration of Mg 2+ microenvironment not only demonstrated better cytocompatibility, but also remarkably enhanced osteogenic differentiation in vitro as compared with the pure PCL and PCL-PEG-PCL co-polymer controls. In the animal studies, we also found that superior and early bone formation and tissue mineralization could be observed in the same 3D printed scaffold. However, the nanocomposite scaffold with high concentration of Mg 2+ jeopardized the in situ bony tissue regeneration capability due to excessive magnesium ions in bone tissue microenvironment. Lastly, this study demonstrates that the nanocomposite 3D scaffold with controlled magnesium concentration in bone tissue microenvironment can effectively promote bone defect repair.

CAS / MDL: 1309-48-4
研究领域: 生物材料学 · 组织工程学 · 再生医学
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JOURNAL OF APPLIED POLYMER SCIENCE · 2021 ·Vol. 138 ·期 37 ·50938 · IF 3.125

Facile fabrication of near-infrared light-responsive shape memory nanocomposite scaffolds with hierarchical porous structures

Jingguang Wang,Zemin Xia,Jian Liu,Naiyue Zhang,Wuyi Zhou,Zichong Zhong,Zhitian Luo,Wenyu Li,Zhuohong Yang,Yang Hu

In this work, the near-infrared (NIR) light-responsive shape memory scaffolds with hierarchical porous structures are designed and facilely formed by freeze drying of 3D printed viscous gel-like pickering emulsions, which are stabilized by hydrophobically modified graphene oxide (g-GO) and silica nanoparticles, and contain thermo-responsive poly( d , l -lactic acid-co-trimethylene carbonate) (PLMC) in the oil phase. The prepared scaffolds display an interconnected filament structure with hierarchical pores and high porosity. The incorporation of g-GO nanoparticles into PLMC matrix prompts that the scaffold shape memory can be triggered by NIR light with fast shape recovery. Moreover, the in vitro mineralization experiment shows that the scaffolds have biological activity, and the drug release study demonstrates that the scaffolds can be used as drug carriers with efficient drug release capacity. Furthermore, cell culture assays based on mouse bone mesenchymal stem cells exhibit that the scaffolds own good cytocompatibility. Therefore, the facile preparation and remote activation of the shape memory nanocomposite scaffolds with hierarchical porous structure and multifunctionality represents a highly attractive candidate as minimally invasive implantation scaffolds for bone tissue engineering applications.

CAS / MDL: 7782-42-5
研究领域: 生物材料学 · 组织工程学 · 医学工程
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ADVANCED FUNCTIONAL MATERIALS · 2022 ·Vol. 32 ·期 18 ·2110931 · IF 19.924

Radially Porous Nanocomposite Scaffolds with Enhanced Capability for Guiding Bone Regeneration In Vivo

Si-Jing Jiang,Mo-Han Wang,Ze-Yu Wang,Huai-Ling Gao,Si-Ming Chen,Yun-Hong Cong,Lu Yang,Shao-Meng Wen,Dong-Dong Cheng,Jia-Cai He,Shu-Hong Yu

An ideal bone repair scaffold is expected to possess superior architectural characteristics to facilitate the adhesion, proliferation, and migration of bone-repair-related cells, while excluding nonosteogenic cells and fibrous tissues from interfering with normal bone regeneration. Unfortunately, such scaffold material has rarely been reported. Herein, nanocomposite scaffolds with a radially ordered porous structure are presented, manufactured using a modified directional freeze-casting method, and are promising bone defect repair materials to satisfy this requirement. The prepared nanocomposite scaffolds consist of a natural bio-macromolecule, chitosan, and bioactive hydroxyapatite nanoparticles derived from porcine cortical bone, demonstrating favorable biocompatibility and biological functions. Both in vitro cell studies and in vivo animal studies reveal the great superiority of the radially oriented porous structure of the scaffolds in guiding bone regeneration, while simultaneously preventing the invasion of surrounding nonosteogenic cells and fibrous tissue, compared to the axially oriented porous structure. This work indicates the distinctive potential of radially oriented porous scaffolds for repairing tabular and lacunar bone defects.

研究领域: 生物医学工程 · 组织工程 · 材料科学
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CHEMICAL ENGINEERING JOURNAL · 2018 · IF 6.735

Cerium-doped whitlockite nanohybrid scaffolds promote new bone regeneration via SMAD signaling pathway

Min Hu,Fei Xiao,Qin-Fei Ke,Yang Li,Xiao-Dong Chen,Ya-Ping Guo

The development of nanoscience, nanohybrid technology and molecular biology provide an important strategy in the construction of novel bone scaffolds. Nanosized whitlockite (WH) and trace cerium (Ce) element exist widely in human bones; however their positive functions on bone cells/tissues still remain unknown. Inspired by the chemical components and nanostructures of bones, Ce-doped WH/chitosan (Ce-WH/CS) nanohybrid scaffolds were developed for new bone regeneration. The Ce-WH/CS scaffolds exhibited interconnected macropores with sizes of ∼300 μm, which facilitated cell adhesion and bone tissue in-growth. Ce-WH nanoparticles with sizes of 10–50 nm were dispersed on macroporous walls. The WH/CS scaffolds with or without doping Ce 3+ ions had non-toxicity to human adipose derived stromal cell (hADSCs). Interestingly, the Ce 3+ ions in the Ce-WH/CS scaffolds significantly improved osteogenic activity via activated SMAD signaling pathway, and up-regulated the expression of osteogenic-related genes including osteocalcin (OCN), osterix (OSX) and collagen 1A1 (COL1A1). Rat cranial defect models further demonstrated that Ce-WH/CS scaffolds remarkably accelerated material biodegradation and bone tissue growth compared to WH/CS scaffolds. The exciting finding revealed the positive functions of Ce-WH nanoparticles on bone tissues, and provided a promising platform for new bone regeneration.

CAS / MDL: 1309-42-8
研究领域: 纳米技术 · 生物材料 · 组织工程 · 分子生物学
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International Journal of Nanomedicine · 2024 · IF 6.6

The Dual Angiogenesis Effects via Nrf2/HO-1 Signaling Pathway of Melatonin Nanocomposite Scaffold on Promoting Diabetic Bone Defect Repair

Tingting Chen,Zimei Wu,Qiaodan Hou,Yixin Mei,Kunkun Yang,Jing Xu,Lin Wang

Purpose Given the escalating prevalence of diabetes, the demand for specific bone graft materials is increasing, owing to the greater tendency towards bone defects and more difficult defect repair resulting from diabetic bone disease (DBD). Melatonin (MT), which is known for its potent antioxidant properties, has been shown to stimulate both osteogenesis and angiogenesis.Methods MT was formulated into MT@PLGA nanoparticles (NPs), mixed with sodium alginate (SA) hydrogel, and contained within a 3D printing polycaprolactone/β-Tricalcium phosphate (PCL/β-TCP) scaffold. The osteogenic capacity of the MT nanocomposite scaffold under diabetic conditions was demonstrated via in vitro and in vivo studies and the underlying mechanisms were investigated.Results Physicochemical characterization experiments confirmed the successful fabrication of the MT nanocomposite scaffold, which can achieve long-lasting sustained release of MT. The in vitro and in vivo studies demonstrated that the MT nanocomposite scaffold exhibited enhanced osteogenic capacity, which was elucidated by the dual angiogenesis effects activated through the NF-E2–related factor 2/Heme oxygenase 1 (Nrf2/HO-1) signaling pathway, including the enhancement of antioxidant enzyme activity to reduce the oxidative stress damage of vascular endothelial cells (VECs) and directly stimulating vascular endothelial growth factor (VEGF) production, which reversed the angiogenesis-osteogenesis uncoupling and promoted osteogenesis under diabetic conditions.Conclusion This study demonstrated the research prospective and clinical implications of the MT nanocomposite scaffold as a novel bone graft for treating bone defect and enhancing bone fusion in diabetic individuals.

研究领域: 生物材料 · 组织工程 · 再生医学 · 糖尿病研究 · 骨生物学 · 药学 · 纳米技术
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Journal of Materials Chemistry B · 2022 ·Vol. 10 ·期 42 ·8719-8732 · IF 7.571

A bioactive poly(ether-ether-ketone) nanocomposite scaffold regulates osteoblast/osteoclast activity for the regeneration of osteoporotic bone

Mengen Zhao,Guo Chen,Shixiong Zhang,Bin Chen,Zhaoying Wu,Chao Zhang

Due to the lower regeneration capacity of the osteoporotic bone, the treatment of osteoporotic defects is extremely challenging in clinics. In this study, strontium-doped bioactive glass nanoparticles loaded with sodium alendronate (ALN), namely A-SrBG, were incorporated into the poly(ether-ether-ketone) matrix to fabricate a bioactive composite scaffold (ASP), which was expected to both inhibit bone resorption and promote bone regeneration. The results showed that such a composite scaffold with interconnected macropores (200–400 μm) could release Ca2+, Sr2+, and ALN in vitro. The proliferation, alkaline phosphatase (ALP) activity, expression of osteogenesis-related genes, and formation of calcified nodules of rat bone marrow stromal cells (rBMSCs) were clearly evidenced, and the reduction in the proliferation, tartrate-resistant acid phosphatase (TRAP) activity, cell fusion, and expression of osteoclastogenesis-related genes of osteoclasts was observed as well. In the presence of the ASP scaffold, enhanced osteogenesis along with inhibiting osteoclastogenesis was observed by modulating the osteoprotegerin (OPG)/receptor activator for nuclear factor κB ligand (RANKL) ratio. The efficacy of the composite scaffold in the regeneration of osteoporotic critical-sized cranial defect in a rat model was evaluated. Therefore, the bioactive composite scaffold with excellent biocompatibility and osteogenic potential could be a promising material for the repair of osteoporotic bone defects.

CAS / MDL: 13477-34-4 10042-76-9
研究领域: 生物材料 · 组织工程 · 骨科 · 生物医学工程
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