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| 1 | Modulating macrophage activities to promote endogenous bone regeneration: Biological mechanisms and engineering approaches显示文摘A coordinated interaction between osteogenesis and osteoimmune microenvironment is essential for successful bone healing.In particular,macrophages play a central regulatory role in all stages of bone repair.Depending on the signals they sense,these highly plastic cells can mediate the host immune response against the exterior signals of molecular stimuli and implanted scaffolds,to exert regenerative potency to a varying extent.In this article,we first encapsulate the immunomodulatory functions of macrophages during bone regeneration into three aspects,as sweeper,mediator and instructor.We introduce the phagocytic role of macrophages in different bone healing periods(‘sweeper’)and overview a variety of paracrine cytokines released by macrophages either mediating cell mobilisation,vascularisation and matrix remodelling(‘mediator’),or directly driving the osteogenic differentiation of bone progenitors and bone repair(‘instructor’).Then,we systematically classify and discuss the emerging engineering strategies to recruit,activate and modulate the phenotype transition of macrophages,to exploit the power of endogenous macrophages to enhance the performance of engineered bone tissue. | Yiming Niu Zhenzhen Wang Yuchen Shi Lei Dong Chunming Wang | 2021 | Bioactive Materials2021，6，1： | 14 |
| 2 | Implantable PEKK/tantalum microparticles composite with improved surface performances for regulating cell behaviors,promoting bone formation and osseointegration显示文摘Polyetherketoneketone(PEKK)exhibits admirable biocompatibility and mechanical performances but bioinert while tantalum(Ta)possesses excellent osteogenesis and osseointegration but high elastic modulus and density,and processing is too difficult and expensive.In the present study,combining of the advantages of both PEKK and Ta,implantable composites of PEKK/Ta were fabricated by blending PEKK with Ta microparticles of 20 v%(PT20)and 40 v%(PT40)content.In comparison with PT20 and PEKK,the surface hydrophilicity,surface energy,roughness and proteins adsorption as well as mechanical performances of PT40 significantly increased because of the higher Ta particles content in PEKK.Furthermore,PT40 exhibited the mechanical performances(e.g.,compressive strength and modulus of elasticity)close to the cortical bone of human.Compared with PT20 and PEKK,PT40 with higher Ta content remarkably enhanced the responses(including adhesion,proliferation and osteogenic differentiation)of MC3T3-E1 cells in vitro.Moreover,PT40 markedly improved bone formation as well as osseointegration in vivo.In short,incorporation of Ta microparticles into PEKK created implantable composites with improved surface performances,which played key roles in stimulating cell responses/bone formation as well as promoting osseointegration.PT40 might have great potential for bear-loading bone substitute. | Xinglong Hu Shiqi Mei Fan Wang Jun Qian Dong Xie Jun Zhao Lili Yang Zhaoying Wu Jie Wei | 2021 | Bioactive Materials2021，6，4： | 6 |
| 3 | 镁离子促进骨再生的分子机制显示文摘背景:近年来,镁离子良好的促进骨再生的作用已得到了实验和临床的广泛认可,含镁植入材料被广泛应用于骨再生,其促进骨再生的分子机制涉及骨环境中的多种细胞及细胞因子,但尚未完全明晰。目的:文章对镁离子促进骨再生的分子机制作一综述。方法:以“magnesium OR magnesium ion”“bone regeneration OR bone repair OR bone repairing OR osteogenesis OR osteanagenesis OR osteanaphysis OR osteoanagenesis”“mechanism OR molecular mechanism OR cell mechanism OR signal pathway OR signaling pathway OR endothelial cell OR vascular OR immune”为英文检索词检索PubMed数据库,以“镁、镁离子”“骨再生、骨修复、骨愈合、骨重建”“机制、分子机制、分子、细胞、信号通路、免疫、血管”为中文检索词检索中国知网和万方数据库。检索时间为建库至2021年12月,按照排除筛选标准纳入文献81篇,对纳入文献进行综述。结果与结论:①对于间充质干细胞,镁离子显著促进其增殖、迁移与黏附、成骨分化,尤其是既可以通过经典Wnt通路、MAPK/ERK通路等直接促其成骨分化,也可通过促进神经节细胞分泌CGRP、巨噬细胞分泌骨形态发生蛋白等细胞因子间接促进成骨分化。②对于成骨细胞,镁离子主要通过TRPM/PI3K信号通路促进其增殖、迁移与黏附、成骨活性,抑制其凋亡。③对于破骨细胞,镁离子主要通过核转录因子κB信号通路抑制破骨细胞形成及骨吸收活性。④镁离子可调节骨环境中的免疫反应,转化巨噬细胞表型,促进促成骨因子分泌,降低炎症因子分泌,降低炎症反应,同时促进血管内皮细胞增殖、迁移与黏附、成血管能力,促进血管生成。⑤镁离子促进骨再生的分子机制丰富,镁离子可通过对调节免疫反应与血管生成从而改善骨再生微环境的分子机制已成为近年来的研究热点,尤其是巨噬细胞的核转录因子κB通路和H型血管内皮细胞对骨再生的作用,共同为骨再生创造了良好的微环境。⑥镁离子促进骨再生的分子机制丰富,但未来仍需大量研究进一步明晰免疫调节和促血管生成对骨再生的分子机制以及镁离子促进骨再生的适宜浓度。 | 张竞心 刘林枫 张士文 林洁 | 2022 | 中国组织工程研究2022，26，33： | 5 |
| 4 | Stratified-structural hydrogel incorporated with magnesium-ion-modified black phosphorus nanosheets for promoting neuro-vascularized bone regeneration显示文摘Angiogenesis and neurogenesis play irreplaceable roles in bone repair.Although biomaterial implantation that mimics native skeletal tissue is extensively studied,the nerve-vascular network reconstruction is neglected in the design of biomaterials.Our goal here is to establish a periosteum-simulating bilayer hydrogel and explore the efficiency of bone repair via enhancement of angiogenesis and neurogenesis.In this contribution,we designed a bilayer hydrogel platform incorporated with magnesium-ion-modified black phosphorus(BP)nanosheets for promoting neuro-vascularized bone regeneration.Specifically,we incorporated magnesium-ion-modified black phosphorus(BP@Mg)nanosheets into gelatin methacryloyl(GelMA)hydrogel to prepare the upper hydrogel,whereas the bottom hydrogel was designed as a double-network hydrogel system,consisting of two interpenetrating polymer networks composed of GelMA,PEGDA,andβ-TCP nanocrystals.The magnesium ion modification process was developed to enhance BP nanosheet stability and provide a sustained release platform for bioactive ions.Our results demonstrated that the upper layer of hydrogel provided a bionic periosteal structure,which significantly facilitated angiogenesis via induction of endothelial cell migration and presented multiple advantages for the upregulation of nerve-related protein expression in neural stem cells(NSCs).Moreover,the bottom layer of the hydrogel significantly promoted bone marrow mesenchymal stem cells(BMSCs)activity and osteogenic differentiation.We next employed the bilayer hydrogel structure to correct rat skull defects.Based on our radiological and histological examinations,the bilayer hydrogel scaffolds markedly enhanced early vascularization and neurogenesis,which prompted eventual bone regeneration and remodeling.Our current strategy paves way for designing nerve-vascular network biomaterials for bone regeneration. | Yan Xu Chao Xu Lei He Junjie Zhou Tianwu Chen Liu Ouyang Xiaodong Guo Yanzhen Qu Zhiqiang Luo Deyu Duan | 2022 | Bioactive Materials2022，7，10： | 5 |
| 5 | 医用金属材料促血管生成的分子机制显示文摘背景:血管生成对于组织修复与再生是必不可少的,提高医用金属材料促血管生成的能力是近年来的研究热点。目的:整理讨论了医用金属材料促内皮细胞血管化的可能分子机制,为后续研发各种促血管生成的医用金属材料奠定基础。方法:检索PubMed、ScienceDirect、中国知网和万方数据库收录的相关文献。英文检索词为“medical metal materials OR alloy”“stent OR scaffold”“vascularization OR angiogenesis”“molecular mechanism OR signaling pathway”“endothelial cells”,中文检索词为“医用金属材料、金属”“支架”“血管化、血管生成”“分子机制、信号通路”“内皮细胞”,最终纳入76篇文献进行分析总结。结果与结论:①医用金属材料植入机体后在降解过程中所释放的金属离子,可以通过促进内皮细胞的增殖、迁移、黏附和提高成管能力来影响血管生成。②镁、锌、铜、锶及钴等金属离子可以激活Wnt、PI3K/Akt、MAPK、缺氧诱导因子1α/血管内皮生长因子等信号通路,上调血管内皮生长因子、血小板衍生生长因子及缺氧诱导因子1α等血管生成因子的表达,促进血管生成相关细胞因子的分泌,从而诱导血管生成。③金属植入体内引起的免疫反应不仅影响植入材料的稳定性,还会影响血管化及成骨效果。④金属离子的浓度会影响血管生成的过程,金属材料降解过快,金属离子爆发积累会导致细胞毒性。确定金属离子最佳促血管化及成骨分化的浓度,是开发多功能金属材料的关键。⑤通过合金化、表面修饰改性等手段提高金属材料的耐腐蚀性,调控金属离子释放速率,有利于营造良好的成骨和血管生成微环境,加速组织的修复与再生。⑥金属促血管生成的机制丰富,但具体分子机制尚未彻底明晰,未来仍需进一步的研究。 | 周岚曦 邵路 董士武 喻正文 | 2023 | 中国组织工程研究2023，27，16： | 3 |
| 6 | Double-edged effects caused by magnesium ions and alkaline environment regulate bioactivities of magnesium-incorporated silicocarnotite in vitro显示文摘Magnesium(Mg)is an important element for its enhanced osteogenic and angiogenic properties in vitro and in vivo,however,the inherent alkalinity is the adverse factor that needs further attention.In order to study the role of alkalinity in regulating osteogenesis and angiogenesis in vitro,magnesium-silicocarnotite[Mg-Ca5(PO4)2SiO4,Mg-CPS]was designed and fabricated.In this study,Mg-CPS showed better osteogenic and angiogenic properties than CPS within 10wt.%magnesium oxide(MgO),since the adversity of alkaline condition was covered by the benefits of improved Mg ion concentrations through activating Smad2/3-Runx2 signaling pathway in MC3T3-E1 cells and PI3K-AKT signaling pathway in human umbilical vein endothelial cells in vitro.Besides,provided that MgO was incorporated with 15wt.%in CPS,the bioactivities had declined due to the environment consisting of higher-concentrated Mg ions,stronger alkalinity and lower Ca/P/Si ions caused.According to the results,it indicated that bioactivities of Mg-CPS in vitro were regulated by the double-edged effects,which were the consequence of Mg ions and alkaline environment combined.Therefore,if MgO is properly incorporated in CPS,the improved bioactivities could cover alkaline adversity,making Mg-CPS bioceramics promising in orthopedic clinical application for its enhancement of osteogenesis and angiogenesis in vitro. | Qiang Wu Shunxiang Xu Fei Wang Bo He Xin Wang Ye Sun Congqin Ning Kerong Dai | 2021 | Regenerative Biomaterials2021，8，6： | 2 |
| 7 | 骨内型镁合金牵引器在犬牙槽骨垂直骨增量中的应用显示文摘背景:牙槽骨牵张成骨由于治疗周期长、二次手术创伤等限制了临床的广泛应用,镁合金作为可降解的生物金属材料可以制作成牵引器解决牙槽骨的软硬组织缺损问题。目的:探讨运用自行研制的骨内型镁合金牵引器垂直牵引犬下颌牙槽骨的可行性。方法:选取9只犬,拔除犬双侧下颌前磨牙,形成萎缩牙槽嵴模型。选取右侧下颌骨为实验侧,左侧为对照侧。3个月后选取右侧下颌骨行骨切开术形成输送盘,并植入1枚牵引器,1周后开始牵张,2次/d,每次0.5 mm,共6 d。固定期3个月后将犬麻醉处死并解剖下颌骨进行大体、X射线片、Micro-CT和组织学观察,并与对照侧进行比较。结果与结论:①9只犬除1只中途死亡并补足后,均成功完成牙槽骨的垂直增高,游标卡尺测量实验侧较对照侧增高4.94 mm;②X射线片检查发现牵张间隙消失,新骨密度增加;取出牵引器可见表面出现腐蚀、降解;③组织学检查可见实验侧活跃的成骨细胞和骨小梁结构,以及部分成熟的骨组织;④Micro-CT检查可见实验侧比对照侧骨小梁与牵张方向更一致(P<0.05);实验侧和对照侧相比骨小梁数目、厚度少量增加但无显著差异(P>0.05),分离度减少(P<0.05),新生骨的骨体积百分比(P<0.05)和矿物质密度(P>0.05)增加;⑤提示自行研制的骨内型镁合金牵引器可以成功增高萎缩的下颌骨,并且骨质愈合良好,可为将来牵引器的研制和临床应用提供参考。 | 王舒 赵贵然 王茹 姚玉胜 屈直 | 2023 | 中国组织工程研究2023，27，25： | 1 |
| 8 | Biofunctionalized composite scaffold to potentiate osteoconduction,angiogenesis,and favorable metabolic microenvironment for osteonecrosis therapy显示文摘Osteonecrosis is a common orthopedic disease in clinic,resulting in joint collapse if no appropriate treatment is performed in time.Core decompression is a general treatment modality for early osteonecrosis.However,effective bone regeneration in the necrotic area is still a significant challenge.This study developed a biofunctionalized composite scaffold(PLGA/nHA30VEGF)for osteonecrosis therapy through potentiation of osteoconduction,angiogenesis,and a favorable metabolic microenvironment.The composite scaffold had a porosity of 87.7%and compressive strength of 8.9 MPa.PLGA/nHA30VEGF had an average pore size of 227.6μm and a water contact angle of 56.5◦with a sustained release profile of vascular endothelial growth factor(VEGF).After the implantation of PLGA/nHA30VEGF,various osteogenic and angiogenic biomarkers were upregulated by 2-9 fold compared with no treatment.Additionally,the metabolomic and lipidomic profiling studies demonstrated that PLGA/nHA30VEGF effectively regulated the multiple metabolites and more than 20 inordinate metabolic pathways in osteonecrosis.The excellent performances reveal that the biofunctionalized composite scaffold provides an advanced adjuvant therapy modality for osteonecrosis. | Tongtong Zhu Mengyang Jiang Mingran Zhang Liguo Cui Xiaoyu Yang Xukai Wang Guangyao Liu Jianxun Ding Xuesi Chen | 2022 | Bioactive Materials2022，7，3： | 1 |
| 9 | Biomimetic Ti-6Al-4V alloy/gelatin methacrylate hybrid scaffold with enhanced osteogenic and angiogenic capabilities for large bone defect restoration显示文摘Titanium-based scaffolds are widely used implant materials for bone defect treatment.However,the unmatched biomechanics and poor bioactivities of conventional titanium-based implants usually lead to insufficient bone integration.To tackle these challenges,it is critical to develop novel titanium-based scaffolds that meet the bioadaptive requirements for load-bearing critical bone defects.Herein,inspired by the microstructure and mechanical properties of natural bone tissue,we developed a Ti-6Al-4V alloy(TC4)/gelatin methacrylate(GelMA)hybrid scaffold with dual bionic features(GMPT)for bone defect repair.GMPT is composed of a hard 3D-printed porous TC4 metal scaffold(PT)backbone,which mimics the microstructure and mechanical properties of natural cancellous bone,and a soft GelMA hydrogel matrix infiltrated into the pores of PT that mimics the microenvironment of the extracellular matrix.Ascribed to the unique dual bionic design,the resultant GMPT demonstrates better osteogenic and angiogenic capabilities than PT,as confirmed by the in vitro and rabbit radius bone defect experimental results.Moreover,controlling the concentration of GelMA(10%)in GMPT can further improve the osteogenesis and angiogenesis of GMPT.The fundamental mechanisms were revealed by RNA-Seq analysis,which showed that the concentration of GelMA significantly influenced the expression of osteogenesis-and angiogenesis-related genes via the Pi3K/Akt/mTOR pathway.The results of this work indicate that our dual bionic implant design represents a promising strategy for the restoration of large bone defects. | Limin Ma Xiaolan Wang Ye Zhou Xiongfa Ji Shi Cheng Dong Bian Lei Fan Lei Zhou Chengyun Ning Yu Zhang | 2021 | Bioactive Materials2021，6，10： | 1 |
| 10 | 生物可降解镁基材料在颅颌面外科的应用及其研究进展显示文摘作为一种新型骨植入材料,生物可降解镁基材料在颅颌面外科显示出广阔的应用前景。与传统骨植入材料相比,镁具有良好的降解特性、生物相容性、力学特性和成骨特性,其降解产物镁离子具有抗凋亡、抗炎的作用,能够促进骨折和骨缺损部位的愈合。多项研究将生物可降解镁基材料应用于颅颌面部骨内固定、引导骨再生技术、骨替代材料、药物负载、种植体表面涂层等领域,其结果显示该类材料能够为骨愈合提供稳定的支持,并发挥出良好的促进成骨作用。此外,镁在口腔其他领域,如牙组织工程、促进软组织愈合等方面也表现出应用潜能,显示出生物可降解镁基材料具有重要的研究价值。 | 常欣楠 刘磊 | 2024 | 国际口腔医学杂志2024，51，1： | 0 |
| 11 | Glycerol solutions of highly concentrated biomineral counter-ions towards water-responsive mineralization: Demonstration on bacterial cellulose and its application in hard tissue repair显示文摘Mineralization has found widespread use in the fabrication of composite biomaterials for hard tissue regeneration.The current mineralization processes are mainly carried out in neutral aqueous solutions of biomineral counter-ions(a pair of cation and anion that form the corresponding minerals at certain conditions),which are stable only at very low concentrations.This typically results in inefficient mineralization and weak control over biomineral formation.Here,we find that,in the organic solvent glycerol,a variety of biomineral counter-ions(e.g.,Ca/PO_(4),Ca/CO_(3),Ca/SO_(4),Mg/PO_(4),or Fe/OH)corresponding to distinct biominerals at significantly high concentrations(up to hundreds-fold greater than those of simulated body fluid(SBF))are able to form translucent and stable solutions(mineralizing solution of highly concentrated counter-ions(MSCIs)),and mineralization can be triggered upon them with external solvents(e.g.,water or ethanol).Furthermore,with pristine bacterial cellulose(BC)membrane as a model,we demonstrate an effective and controllable mineralization performance of MSCIs on organic substrates.This approach not only forms the homogeneous biominerals on the BC fibers and in the interspaces,but also provides regulations over mineralization rate,mineral content,phase,and dopants.The resulting mineralized BC membranes(MBCs)exhibit high cytocompatibility and favor the proliferation of rat bone marrow mesenchymal stem cells(rBMSC).Following this,we prepare a mineralized bone suture(MBS)from MBC for non-weight bearing bone fixation,which then is tested on a rabbit median sternotomy model.It shows firm fixation of the rabbit sternum without causing discernible toxicity or inflammatory response.This study,by extending the mineralization to the organic solution system of highly concentrated counter-ions,develops a promising strategy to design and build targeted mineral-based composites. | Yunfei Zhao Xiaohao Liu Zhi Zhou Chaobo Feng Nan Luo Jiajun Yan Shuo Tan Yang Lu Feng Chen Bing-Qiang Lu Shisheng He | 2024 | Nano Research2024，17，3： | 0 |
| 12 | 3D打印磷酸镁铵/聚己内酯引导骨再生支撑性膜的制备及其生物学性能的研究显示文摘目的:制备一种新型3D打印磷酸镁铵/聚己内酯(MNP/PCL)复合引导骨再生(GBR)膜,探究MNP添加比例对材料力学性能及生物学性能的影响。方法:利用熔融沉积成型3D打印技术成功制备纯PCL膜和MNP/PCL复合膜(MNP质量比例:5%和10%),随后对各组的表面形貌及力学性能进行分析,并通过体外细胞学实验检测其生物相容性及促成骨性能。结果:扫描电子显微镜图像显示,每个PCL和MNP/PCL膜都呈现出互连的网络结构,5%MNP/PCL和10%MNP/PCL打印丝径和孔径与预先设计的打印模型相符。相较于纯PCL膜,MNP/PCL膜表现出更优秀的机械强度和亲水性(P<0.01)。体外细胞实验表明,MNP/PCL膜具有良好的细胞黏附性,并显著促进了MC3T3E1的增殖和成骨能力(P<0.05)。结论:3D打印MNP/PCL复合膜兼具良好的生物相容性、机械性能和促成骨能力,为临床工作中GBR所面临的困境提供新思路。 | 刘蕴贤 朱蓉蓉 常晓峰 李哲 | 2023 | 实用口腔医学杂志2023，39，6： | 0 |
| 13 | 激光增材制造WC_(p)钛基复合材料界面连接机理及力学性能显示文摘颗粒增强金属基复合结构件在航空航天、机械制造以及电子电工等领域有着广泛的应有前景。文中选用激光增材选区熔化技术制备碳化钨(WC)颗粒增强TC4复合材料(WC/TC4),研究了WC颗粒含量和激光功率对复合材料微观组织和力学性能的影响。结果表明,随着WC颗粒含量的增加,复合材料宏观试样成形能力降低,在WC颗粒含量为(0%~15%)时,WC颗粒分布较为均匀,未见微气孔、裂纹的出现,当颗粒含量为20%时,材料内部出现气孔和裂纹,难以成形;在WC/基体的界面处形成了一层TiC和W_(2)C界面层,界面结合性能良好;随着复合材料内部颗粒含量和激光功率的增加,材料的断裂强度和断后伸长率降低,断裂机理主要为WC颗粒的脆性断裂和沿WC-W_(2)C界面的层状撕裂。 | 吴诚福 李新意 陈洪胜 李健 聂慧慧 王文先 | 2023 | 机械制造文摘(焊接分册)2023，，6： | 0 |
| 14 | 金属元素在促进骨再生中的作用及机制显示文摘颌骨缺损修复始终是临床上面临的重大难题,这也推动了对骨缺损修复材料的深入研究。目前对于能更好实现临床应用的人工骨缺损修复材料,除了追求优异的力学性能、生物相容性等,材料的生物学活性尤其是促成骨性能也逐渐受到重视,很多研究在材料表面改性、纳米形貌修饰、添加生物活性离子或涂层等方面不断创新。本文就近年通过利用不同金属元素的作用来增强骨修复材料的成骨性能的研究进展做一综述,重点阐述现有研究中哪些金属离子可以发挥促成骨作用,对细胞产生何种影响以及相关的分子机制,除此之外,本文还总结了一些金属元素促进成骨常见的分子信号通路和共性机制,希望可以为后续相关研究提供思路,为骨修复材料的改性创新提供参考。 | 刘子杨 李雅欣 刘加强 | 2023 | 口腔颌面修复学杂志2023，24，1： | 0 |
| 15 | 激光增材制造WC_(p)钛基复合材料界面连接机理及力学性能显示文摘颗粒增强金属基复合结构件在航空航天、机械制造以及电子电工等领域有着广泛的应有前景.文中选用激光增材选区熔化技术制备碳化钨(WC)颗粒增强TC4复合材料(WC/TC4),研究了WC颗粒含量和激光功率对复合材料微观组织和力学性能的影响.结果表明,随着WC颗粒含量的增加,复合材料宏观试样成形能力降低,在WC颗粒含量为(0%~15%)时,WC颗粒分布较为均匀,未见微气孔、裂纹的出现,当颗粒含量为20%时,材料内部出现气孔和裂纹,难以成形;在WC/基体的界面处形成了一层TiC和W_(2)C界面层,界面结合性能良好;随着复合材料内部颗粒含量和激光功率的增加,材料的断裂强度和断后伸长率降低,断裂机理主要为WC颗粒的脆性断裂和沿WC-W2C界面的层状撕裂. | 吴诚福 李新意 陈洪胜 李健 聂慧慧 王文先 | 2023 | 焊接学报2023，44，3： | 0 |
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