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Reconstructing avascular necrotic femoral head through a bioactiveβ-tcp system:From design to application

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Bioactive Materials 2023年第10期28卷 495-510页

作者： Yajie Lu Xiantao Chen Xiao Lu Changning Sun Minghui Li Guojing Chen Zuoyao Long Yuan Gao Haoqiang Zhang Mengquan Huang Chuanlei Ji Hongbin Fan Dong Liu Yuewen Hao Hong Wang Leilei Zhang Hongmei Zhang Jianxi Lu Zhen Wang Jing Li Department of Orthopedics Xijing HospitalAir Force Medical UniversityXi’an710032China Department of Clinical Oncology Xijing HospitalAir Force Medical UniversityXi’an710032China The State Key Laboratory of Cancer Biology Biotechnology Center School of PharmacyAir Force Medical UniversityXi’an710032China Department of Osteonecrosis of the Femoral Head Luoyang Orthopedic-Traumatological Hospital of Henan ProvinceLuoyang471002China Shanghai Bio-lu Biomaterials Co. LtdShanghai201100China Shanghai Technology Innovation Center of Orthopedic Biomaterials Shanghai201100China State Key Laboratory for Manufacturing System Engineering Xi’an Jiaotong UniversityXi’an710054China National Medical Products Administration(NMPA)Key Laboratory for Research and Evaluation of Additive Manufacturing Medical Devices School of Mechanical EngineeringXi’an Jiaotong UniversityXi’an710054China Department of Orthopedics General Hospital of Northern Theater CommandShenyang110000China Department of Orthopedics The 940th Hospital of Joint Logistics Support Force of People’s Liberation ArmyLanzhou730000China Department of Medical Imaging Xi’an Children’s HospitalXi’an710000China Department of Medical Imaging Xijing HospitalAir Force Medical UniversityXi’an710032China

A variety of techniques have been used for treating avascular necrosis of the femoral head(ANFH),but have frequently failed.In this study,we proposed aβ-tcp system for the treatment of ANFH by boosting revascularization and bone regeneration.The angio-conductive properties and concurrent osteogenesis of the highly interconnected porousβ-tcp scaffold were revealed and quantified through an in vivo model that simulated the ischemic environment of ANFH.Mechanical test and finite element analysis showed that the mechanical loss caused by tissue necrosis and surgery was immediately partially compensated after implantation,and the strength of the operated femoral head was adaptively increased and eventually returned to normal bone,along with continuous material degradation and bone regeneration.For translational application,we further conducted a multi-center open-label clinical trial to assess the efficacy of theβ-tcp system in treating ANFH.Two hundred fourteen patients with 246 hips were enrolled for evaluation,and 82.1%of the operated hips survived at a 42.79-month median follow-up.The imaging results,hip function,and pain scores were dramatically improved compared to preoperative levels.ARCO stage II disease outperformed stage III in terms of clinical effectiveness.Thus,bio-adaptive reconstruction using theβ-tcp system is a promising hip-preserving strategy for the treatment of ANFH.

关键词： Avascular necrosis of the femoral head β-tcp Vascularization Bone regeneration Clinical trial Bioadaptability

Biological and mechanical investigation of novel flax/silk protein-based nanofibrous scaffold for bone regeneration

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Progress in Natural Science:Materials International 2022年第4期32卷 443-455页

作者： M.Rama U.Vijayalakshmi Department of Chemistry School of Advanced Sciences Vellore Institute of Technology

The process of bone tissue regeneration involves an intricate network of a biological macromolecules that includes proteins and peptides to support stimulation and healing response. Here, we have fabricated a novel flaxseed/silk fibroin based(dual protein) composite nanofibers using β-tcp to improve the biological properties and promote cartilage tissue regeneration along with a controllable rate of biodegradation. The physiochemical properties of PVA/β-tcp/FP:SF were characterized by FTIR, XRD, SEM, porosity, contact angle measurements and mechanical evaluation etc. This study demonstrates the biological performance of the developed nanofibers by using hemocompatibility, biodegradation ability, and apatite deposition in stimulated body fluid. Moreover, the cell viability assay was performed on MG-63 osteoblast cells and long-term antibacterial rate against E. coli and S. aureus was analysed. Docking results of flax protein and silk fibroin protein further confirmed the stable modes of intramolecular bonding and the most stable electrostatic values using theoretical calculations. Taken together,the experimental results proved that the dual protein-based fibrous scaffold was found to be up-regulated in terms of biological activity with enhanced cell adhesion and proliferation.

关键词： Flax protein Silk fibroin β-tcp Electrospinning Docking Bone regeneration

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双相磷酸镁钙微球体外成血管和促成骨研究

无机材料学报 2023年第7期38卷 830-838,I0009页

作者：吴未 BAKHET Shahd ASANTE Naomi Addai KAREEM Shefiu KOMBO Omar Ramadhan 李宾斌戴红莲武汉理工大学深圳研究院深圳518000 武汉理工大学材料复合新技术国家重点实验室湖北省生物材料工程研究中心武汉430070 姆贝亚科技大学医学科学与技术系坦桑尼亚姆贝亚

磷酸三钙(β-tcp)陶瓷替代材料由于其与骨矿物成分相近及良好的生物相容性和骨传导性,近年来被广泛关注,常以纳米颗粒、支架和微球等形式用于骨修复。本研究制备了五种不同的磷酸三钙/磷酸三镁(TMP)(tcp、25%TMP、50%TMP、75%TMP和TMP)... 详细信息

磷酸三钙(β-tcp)陶瓷替代材料由于其与骨矿物成分相近及良好的生物相容性和骨传导性,近年来被广泛关注,常以纳米颗粒、支架和微球等形式用于骨修复。本研究制备了五种不同的磷酸三钙/磷酸三镁(TMP)(tcp、25%TMP、50%TMP、75%TMP和TMP)复合微球并作了相应表征。随着复合微球中TMP含量增加,微球释放的Mg^(2+)和Ca^(2+)的累积浓度增加,且TMP可以调节复合微球的降解速率。以小鼠胚胎成骨细胞前体细胞(MC3T3-E1)和人脐静脉内皮细胞(HUVECs)为模型,评价了该复合微球的生物相容性、成血管和成骨作用。结果表明,与tcp、TMP和75%TMP相比,25%TMP和50%TMP复合微球具有更好的细胞相容性,对HUVECs有一定的促增殖作用。因此,含25%TMP和50%TMP的复合微球对血管生成和成骨具有更积极的作用。

关键词： β-tcp TMP 骨缺损陶瓷微球骨组织工程

Preparation and properties of β-tricalcium phosphate porous bioceramic

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中国有色金属学会会刊：英文版 2004年第5期14卷 981-986页

作者：张士华熊党生崔崇 Department of Materials Science and Engineering Nanjing University of Science and Technology Nanjing 210094 China

Porous β-tricalcium phosphate bioceramic （Ptcp） has important roles in surgical implants because of good biocompatibility. But the low compressive strength of the ceramic limits its application. The preparation of Ptcp was improved with the adjustment of the constituents and the sintering-process. A new type of Ptcp material with high compressive strength was made. The compositions, microstructure and properties of Ptcp were analyzed by TG-DSC, XRD, TEM, SEM and so on. The result indicates that stearic acid burns sufficiently and gives out carbon dioxide and water vapor when slowly heated between 200 ℃ and 400 ℃ so that the porous structure like coral in β-tcp bioceramic is formed. Through crystallization at 470 ℃ and 570 ℃, more CaO-P2O5 glass-cement is converted into crystallite-glass, which is beneficial for improving the compressive strength of β-tcp bioceramic. Ptcp can form a support action in bone imperfect section with good solubility.

关键词： TG-DSC β-tcp 金属陶瓷电子显微镜扫描电镜 x射线衍射多孔陶瓷生物材料生物降解

β-tcp强化锌镁基复合材料的微观组织与性能研究

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太原理工大学学报 2022年第5期53卷 807-812页

作者：胡永金王文先崔泽琴太原理工大学材料科学与工程学院太原030024

纯锌有良好的生物相容性和适中的降解速率,但力学性能不理想,限制了其生物医学应用。针对纯锌力学性能较差的问题,利用高能球磨和放电等离子烧结技术制备具有核壳结构的Zn-10Mg-xβ-tcp(x=0,1,3,5)复合材料,选用磷酸三钙(β-tcp)作为增... 详细信息

纯锌有良好的生物相容性和适中的降解速率,但力学性能不理想,限制了其生物医学应用。针对纯锌力学性能较差的问题,利用高能球磨和放电等离子烧结技术制备具有核壳结构的Zn-10Mg-xβ-tcp(x=0,1,3,5)复合材料,选用磷酸三钙(β-tcp)作为增强相,以改善纯锌的力学性能和腐蚀性能。对Zn-10Mg-xβ-tcp(x=0,1,3,5)复合材料的微观组织、力学性能和腐蚀性能进行研究。结果表明,所有试样致密度均在95%以上,其中Zn-10Mg-1β-tcp由于β-tcp少量加入产生了弥散强化和位错强化作用,微纳力学硬度明显高于其他试样,达到4.008 GPa;抗压强度和抗弯强度分别为397 MPa和92 MPa,延伸率为6.5%;电化学实验中,Zn-10Mg-1β-tcp的腐蚀电流与锌镁合金相差不大,明显高于其他试样;在长期的浸泡实验中,试样Zn-10Mg-1β-tcp的平均腐蚀速率(0.221 mm/a)最大,并符合植入材料的降解速率要求。

关键词： β-tcp 放电等离子烧结核壳结构可降解材料锌镁合金

Controlling calcium and phosphate ion release of 3D printed bioactive ceramic scaffolds: An in vitro study

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Journal of Advanced Ceramics 2017年第2期6卷 157-164页

作者： Lukasz WITEK Yang SHI James SMAY Department of Biomaterials and Biomimetics College of Dentistry New York University New York NY USA School of Chemical Engineering Oklahoma State University Stillwater OK USA School of Materials Science and Engineering Oklahoma State University Tulsa OK USA

This paper characterizes in an in vitro setting the release of calcium (Ca) and phosphate (PO4) of 3D printed bioactive ceramic scaffold prepared from extrudable paste containing hydroxyapatite and β-tricalcium phosphate (β-tcp). Hydroxyapatite and β-tcp were calcined at 800 °C for 11 h, fabricated into four experimental groups (100% HA, 100% β-tcp, 15%/85% HA/β-tcp, and 15%/85% HA/β-tcp (design)), sintered to 1100 °C for 4 h. Calcium and phosphorus concentrations were evaluated using ICP spectroscopy, and the release of Ca and PO4 ions during dissolution of the CaP-based scaffolds was measured by submerging in 0.05 mol/L Tris(hydroxymethyl)aminomethane-HCl and maintaining a temperature of 37 °C. The Ca and PO4 concentrations of the solutions were measured with the utilization of a calcium assay kit and a phosphate assay kit and read in a UV–visible spectrophotometer. The 100% HA scaffold group showed the greatest concentration of Ca ions (~1.9 mg/dL), but ultimately released at a lower amount as time increased; the 100% HA scaffold also showed the lowest total amount of calcium ions released over the course of evaluation. The results for the 100% β-tcp were on the opposite of the HA with the highest amount of calcium ion release over the study. While the PO4 ion release showed a similar trend as those observed with Ca ions with an apparent difference in the 100% HA scaffold group. There was nearly 0 mg/dL of the phosphate ions released in the first 24 h, in comparison to the amount of Ca ions released during the same time frame. Since various formulations can lead to different properties of these bioactive ceramic scaffolds, it is important to understand how the tailoring of this important biphasic material can impact the long-term outcome of an ever-important in vivo clinical trial in the future.

关键词： 3D printing β-tcp scaffolds in vitro calcium phoshpate

STUDIES ON THE BIODEGRADATION MECHANISM OF β-TRICAICIUM PHOSPHATE CERAMICS

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Journal of Wuhan University of Technology(Materials Science) 1997年第4期12卷 1-6页

作者：阎玉华 Wuhan University of Technology China Res. Ctr. of Med. Mat./Engineering Wuhan University of Technology Wuhan 430070 China Xiehe Hospital Tongji Medical University China 203 Hospital Chinese People's Liberation Army China

In order to clarify the biodegradation mecha-nism of?-tricalcium phosphate (β-tcp) ceramics, In vitro and In vivo experiments have been carried out. Nanometric microelectrodes were applied to measure the pH values in-side and outside phagocytes which were cultured for 72 hours respectively in (β-tcp-bearing and (β-tcp-free medi-um. Radioactive isotope 45 Ca was used to trace the distribu-tion and metabolism process of degraded products. We found that the degradation of (β-tcp ceramics was due to the dis-solving process in body fluid and the degrading process me-diated by cells. After (β-tcp ceramics labelled by 45 Ca were implanted into rabbits,radioactive 45 Ca was tested in blood, faece and organs such as heart, kidney and stomach etc. It was also found in the nearby new bone. So,we think a small part of the degraded products enter the animal's blood and take part in the metabolism of body . Others are reused to form new bone. The reports from clinical application also gave us strong support.

关键词： β-tcp biodegradation metabolism

Effects of β-Tricalcium Phosphate on the Growth of Rat Osteoblasts

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Journal of Wuhan University of Technology(Materials Science) 2005年第B12期20卷 187-189页

作者：袁琳 Biomedical Materials and Engineering Research Center Wuhan University of Technology Wuhan 430070 China

Calcium-phosphate materials, such as β- tcp could be degraded in vivo , and in the cultured cells in vitro. However , it is still unknown how the materials changed the activity of the cells. In order to understand the mechanism of β- tcp treatment on osteoblasts , cell proliferation rate measurement and microscopic observation were performed during co-culture of rat osteoblasts and β- tcp biomaterials. It was observed that low concentrations of β- tcp-treated cell proliferation rate was a little less than control by MTT assay, while higher concentratioras of β- tcp-treated cell proliferation rate was more than control. The proliferation rate of osteoblast treated by β-tcp with bioglass had a similar effect with β-tcp-treated cell. Neither calcium chloride nor sodium monophosphate treatment could stimulate the cell proliferation at the concentration from 0.25 mM to 5 mM. During the treatment of β- tcp , particles could be found in the cells. It suggested that β- tcp could stimulate cell proliferation rate of rat osteoblast with or without bioglass , while Ca^2＋ and PO4^3＋（ provided by calcium chloride and sodium monophosphate , separately）, the degraded products of β- tcp had no significant effect on osteoblast cell growth in a wide range. The stimulating effect of β- tcp on osteoblast cell proliferation might relate to the encapsulation of the ruclterial particles into the cells.

关键词： β-tcp osteoblast cell proliferation

3D打印模具法制备磷酸三钙点阵支架工艺研究

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中国陶瓷 2023年第10期59卷 43-49页

作者：马热艳木·艾尼乌日开西·艾依提王江华滕勇贾儒新疆大学机械工程学院乌鲁木齐830047 中国人民解放军新疆军区总医院乌鲁木齐830000

通过数字光处理(DLP)3D打印技术制备模具,并与凝胶注模成型工艺相结合,制备了固含量为60%的OP、QD两种形式的β-磷酸三钙(β-tcp)点阵结构支架。分析了两种点阵结构支架的物相、微观形貌、孔隙率、收缩率以及力学性能。实验结果表明:点... 详细信息

通过数字光处理(DLP)3D打印技术制备模具,并与凝胶注模成型工艺相结合,制备了固含量为60%的OP、QD两种形式的β-磷酸三钙(β-tcp)点阵结构支架。分析了两种点阵结构支架的物相、微观形貌、孔隙率、收缩率以及力学性能。实验结果表明:点阵结构支架在烧结之后没有发生物相变化,晶粒之间链接紧密。支架的孔隙直径为540~570μm;OP点阵结构支架的总孔隙率为65.06%,QD结构为64.18%;两种形式支架的收缩率接近,分别为15.25%和15.84%;OP结构支架的最大抗压强度6.95 MPa,QD结构支架为4.26 MPa。两种点阵结构支架力学性能都松质骨的抗压强度范围内。

关键词： 3D打印凝胶注模成型骨组织工程支架点阵结构 β-tcp