硅酸盐生物活性陶瓷研究进展

生物陶瓷经历了由惰性生物陶瓷如氧化铝和氧化锆陶瓷到可降解生物陶瓷如磷酸三钙陶瓷及具有生物活性的生物陶瓷如羟基磷灰石陶瓷的发展过程。近年来,随着再生医学研究和组织工程技术的发展,对生物材料的性能有了更高的要求,有学者提出了第三代生物材料的概念,认为新一代生物材料应该既具有生物活性,又可降解。研究发现,一些含硅的生物玻璃兼具有这两种特性,其生物活性体现在可以在模拟体液或体内环境中诱导形成类骨磷灰石,这种类骨磷灰石可以与骨组织形成键合。此外,研究显示这类生物玻璃材料具有促进细胞增殖和成骨基因表达的作用。但是,生物活性玻璃存在不易再加工成型,进一步热处理后生物活性和降解性会发生变化等问题。在生物玻璃研究的基础上,研究了一系列钙-硅体系的硅酸盐陶瓷,证实了这类生物陶瓷具有良好的生物活性和降解性,其生物活性和降解性与其化学组成有密切的关系,细胞实验显示这类硅酸盐陶瓷也具有促进细胞增殖分化和骨组织再生的作用,有望成为新一代骨修复材料。     

生物陶瓷支架促进再生组织血管生成和骨生成的研究进展

近年来,组织工程作为一种有前景的治疗和修复骨缺损的方法受到了广泛的关注.支架是组织工程的基本组成部分,它能够为骨组织再生提供必要的支撑和导向作用.骨组织修复过程中需要在支架内部形成一个血管网络来为细胞迁移、增殖和分化提供营养和氧气,从而实现组织再生.因此,组织工程血管化是实现骨组织再生的首要前提.生物陶瓷凭借其特殊的化学成分、高的压缩强度和优异的生物活性,成为骨再生支架的有力候选材料.然而,生物陶瓷支架在植入体内后,往往需要较长的时间才能形成血管网络.这就意味着组织内部的细胞会因长时间缺乏营养而死亡,影响组织再生效果.因此,近些年来,除研究材料成分对再生组织的血管生成和骨生成效果的影响外,研究者还从支架结构设计和支架外部的环境因素着手,以进一步提高生物陶瓷支架诱导血管生成和骨生成的能力.生物复合陶瓷不仅能提高支架的力学性能,还能改善支架的生物活性.分级多孔设计可以模拟自然骨的结构,从而更好地促进再生组织的血管化和骨生成.加载生长因子、元素掺杂和细胞植入可以为血管化提供更好的外部环境,从而更好地实现组织再生.这些因素可以协同发挥作用来促进生物陶瓷支架的血管生成和骨生成.本文从三个方面总结了影响生物陶瓷支架促进再生组织血管生成和骨生成的因素——支架材料、支架结构和支架所处的环境,并系统分析了以上因素的影响机理.最后,展望了生物陶瓷支架的发展趋势,以期为生物陶瓷的设计、加工和生物工程应用提供参考.     

β-磷酸三钙/硅酸钙复合生物陶瓷的制备及性能研究

以β-磷酸三钙/硅酸钙(β-TCP/CS)纳米复合粉体为原料, 制备了质量比为50:50的β-TCP/CS复合生物陶瓷. 研究表明, 1150℃烧结5h得到的样品强度最好, 其致密度>96%, 晶粒尺寸约120nm, 强度达126MPa、同人体致密骨相当; 复合陶瓷在模拟体液中浸泡1天表面就全部被类骨羟基磷灰石层覆盖住, 28天的降解率达10.1%, 具有良好的生物活性和降解性. 研究结果显示β-TCP/CS复合生物陶瓷有望作为强度较好的可降解生物活性硬组织修复材料.     

多孔硅酸钙生物陶瓷的制备及体外活性和降解性研究

以聚乙二醇为造孔剂,制备了多孔硅酸钙生物陶瓷.应用本文提供的方法,可制得孔连通性好、气孔率53.7%-73.6%、抗压强度4.9-48.5MPa、大孔孔径200-500μm的多孔陶瓷.研究表明,多孔硅酸钙生物陶瓷的力学强度随造孔剂含量的增加而明显降低,而气孔率则相反.应用模拟体液浸泡实验研究了多孔陶瓷的体外生物活性和降解性.研究表明,样品在模拟体液中浸泡1天表面就全部被碳酸代羟基磷灰石层覆盖住.气孔率为63.1%的样品7天的降解率达7.14%,具有良好的降解性.研究结果显示多孔硅酸钙生物陶瓷有望作为硬组织修复支架材料用.     

生物陶瓷支架的功能改性及应用研究进展

生物陶瓷支架具有良好的生物相容性和引导组织再生特性, 并可提供多孔的表面形貌和孔道结构, 以促进新生组织的长入, 在硬组织修复和骨组织工程支架领域获得了广泛的关注和临床应用。当前, 生物陶瓷支架仍然存在骨诱导活性差、生物功能单一、力学性能差等缺陷, 极大限制了它们的临床治疗效果和应用范围。本文从生物陶瓷支架的功能改性角度出发, 对材料实施表面功能涂层修饰、微纳结构改性、功能元素掺杂、力学增强等策略, 及其在改善植入体生物相容性、促进成骨活性、药物递送、抗肿瘤和抗菌等方面的应用进展进行了归纳和总结, 并对功能改性生物陶瓷支架的未来发展趋势作了展望。     

硬组织修复材料的骨再生机理研究

传统硬组织修复材料由于在组成及结构上与人体骨组织存在较大差异,植入体内后的骨组织修复过程基本上是一种被动的"充填"过程,且材料的降解速度与新骨形成速度不匹配,难以达到真正的"生物性融合",严重制约了该类材料在骨科临床的推广应用。因此,设计与制备具有"主动修复功能"和"可调控生物响应特性"的第3代新型硬组织修复材料已成为当前骨科临床的新需求和未来的发展方向。介绍了硬组织修复材料的骨再生机理研究方法,综述了硬组织修复材料与宿主防御和骨再生及宿主微环境对材料与宿主细胞相互作用的研究现状。指出硬组织修复材料植入体内后所发生的序列事件可能通过表观遗传修饰使得基因表达受材料本身和宿主微环境等因素的调控,提出新型硬组织修复材料研究中存在的问题和发展趋势。     

光固化3D打印磷酸钙基生物陶瓷支架的研究进展

磷酸钙基生物陶瓷多孔支架是临床中实现骨缺损再生修复的常用骨移植物。光固化3D打印技术以其优异的打印精度和复杂结构成形特性能够精确地控制支架孔尺寸、孔形状、孔连通率,在制备生物陶瓷多孔支架领域展现出巨大的应用潜力。然而,利用光固化3D打印技术制备磷酸钙基生物陶瓷多孔支架仍面临亟需克服的挑战,如缺乏性能优异的磷酸钙基陶瓷打印浆料、打印及后处理工艺不成熟、制备的磷酸钙基陶瓷多孔支架的性能还有待提升。本文首先介绍了几种常用的光固化3D打印技术基本原理与特征,然后从3D打印成形工艺、力学性能、生物活性、支架结构及功能化等方面系统探讨了光固化3D打印技术在制备磷酸钙基生物陶瓷多孔支架领域的研究进展及存在的问题,最后展望了光固化3D打印磷酸钙基生物陶瓷多孔支架的发展趋势和突破点,为利用光固化3D打印技术制备成本低、综合性能优异的磷酸钙基生物陶瓷多孔支架提供参考。     

Li2Ca2Si2O7生物陶瓷的矿化活性研究

如何有效治疗牙周炎并实现受损牙周骨组织再生, 一直是牙周疾病治疗中具有挑战性的问题, 而矿化是牙周正常发育和功能中关键因素之一。本研究旨在探讨硅酸钙锂(Li₂Ca₂Si₂O₇)生物陶瓷对人牙周膜成纤维细胞增殖、矿化的影响及用于牙周骨组织再生的可能性。采用溶胶-凝胶法制备合成了Li₂Ca₂Si₂O₇陶瓷粉体。通过体外模拟体液浸泡, 发现Li₂Ca₂Si₂O₇粉体具有良好的羟基磷灰石矿化能力。生物学结果表明: Li₂Ca₂Si₂O₇粉体的浸提液在3.125~25 mg/mL浓度范围内能显著促进HPLFs的增殖, 低浓度(6.25 mg/mL)时可显著诱导HPLFs细胞体外矿化(p<0.05)。Li₂Ca₂Si₂O₇粉体具有促进人牙周膜成纤维细胞增殖和矿化能力, 有望作为牙周骨组织再生修复的生物活性材料。     

骨修复用生物玻璃复合材料研究进展

生物玻璃是一类性能优良的生物材料,具有良好的生物活性和生物相容性,作为骨修复植入体可以在材料界面与人体骨组织之间形成化学键合,诱导骨的修复与再生.将生物玻璃与其它材料进行复合,可以制备出生物活性和机械性能优良的骨修复复合材料.综述了生物玻璃复合材料的研究现状,并探讨了该类材料目前存在的不足,展望了其发展趋势.     

硅替代纳米羟基磷灰石的研究进展

硅元素掺杂羟基磷灰石可有效提高移植骨组织生物活性和生物相容性,在骨修复材料领域有着广泛的研究。概述了硅元素在骨修复材料中的作用,硅替代纳米羟基磷灰石粉体的制备、表征方法、替代机理及硅替代羟基磷灰石生物陶瓷在体内、体外实验中的最新研究成果,同时综述了硅替代羟基磷灰石目前存在的一些问题和其在骨修复材料方面的发展前景。     

Black Bioceramics: Combining Regeneration with Therapy

Bioceramics have been developed from bioinert to bioactive or biodegradable materials in the past few decades. However, at present, traditional bioceramics are still mainly used in bone tissue regeneration and dental restoration. In this work, a new generation of “black bioceramics,” extending the applications from tissue regeneration to disease therapy, is presented. Black bioceramics, through magnesium thermal reduction of traditional white ceramics, including silicate-based (e.g., CaSiO₃, MgSiO₃) and phosphate-based (e.g., Ca₃(PO₄)₂, Ca₅(PO₄)₃(OH)), are successfully synthesized. Due to the presence of oxygen vacancies and structural defects, the black bioceramics possess photothermal functionality while maintaining their initial high bioactivity and regenerative capacity. These black bioceramics show excellent photothermal antitumor effects for both skin and bone tumors. At the same time, they have significantly improved bioactivity for skin/bone tissue repair in vitro and in vivo. These fascinating properties award the black bioceramics with profound applications in both tumor therapy and tissue regeneration, which should greatly promote the scientific relevance and clinical application of bioceramics, representing a promising new direction of cell-instructive biomaterials.     

Promising trends of bioceramics in the biomaterials field

Biomedical scientific community is currently demanding new advances in the designing of 3rd generation bioceramics, which promote bone tissue regeneration. In the last years, the development of supramolecular chemistry and the application of organic-inorganic hybrid materials in the biomedical field have resulted in a new generation of advanced bioceramics, which exhibit fascinating properties for regenerative purposes together with the possibility of being used as carriers of biologically active molecules. This communication overviews the evolution occurred from the first silica based bioceramics to the last advances in the synthesis of bioceramics for bone tissue regeneration. A critical review concerning the first bioactive glasses as well as the newest hybrid bioactive materials and templated mesoporous bioactive systems, will be performed from the point of view of their potential applications as replacement materials in bone repair and regeneration.     

The influences of poly(lactic-co-glycolic acid) (PLGA) coating on the biodegradability, bioactivity, and biocompatibility of calcium silicate bioceramics

Calcium silicate (CaSiO₃) bioceramics and polyesters have complementary qualities as potential bone substituted materials. In this study, sintered CaSiO₃ bioceramics were prepared and coated with poly(lactic-co-glycolic acid) (PLGA), and the influences of the PLGA coating on the degradation, hydrophilicity, bioactivity, and biocompatibility of CaSiO₃ ceramics were investigated. The results showed that the degradation rate was reduced, while hydrophilicity was decreased with the increase of the polymer coating. In addition, the polymer coating resulted in a decrease of the alkaline pH value during the degradation of the ceramics, which indicated an increase of the cell biocompatibility, confirmed by the attachment and proliferation of rMSCs on the surface of the polymer-coated ceramics. Furthermore, the apatite-forming ability of the PLGA-coated CaSiO₃ bioceramics was maintained. This study suggested that the coating with PLGA might be a useful method to improve the integrative properties of CaSiO₃ bioceramics for applications in bone regeneration and bone tissue engineering.     

光固化生物陶瓷功能化研究进展EI北大核心CSCD

光固化制备陶瓷成为近年来快速发展的增材制造技术之一。生物陶瓷材料凭借良好的细胞相容性,在组织工程领域具有广阔前景,然而单一的生物陶瓷材料难以兼顾力学性能与生物相容性,其应用与推广受到极大限制。本文综述了适用于光固化的生物陶瓷材料改性及设计方法,重点讨论了材料改性、表面改性、结构设计以及微结构调控对于骨传导、骨诱导、抗菌、促进血管生成等生物性能及基础力学性能的综合影响,并指出通过改性及调控方法的组合探究多功能的实现及相互影响机理,能够充分实现光固化生物陶瓷的功能,推动其深层次应用。     

多孔硅酸钙生物陶瓷体内非骨性环境的植入研究

采用泡沫浸渍法制备了多孔硅酸钙(CS)和β-磷酸三钙(β-TCP)生物陶瓷材料, 将其植入家兔皮下筋膜组织中以研究其非骨性环境下的生物学行为. CS, β-TCP分别植入1、2、4周后取材, 采用SPECT、Micro-CT、V-G染色、SEM、EDX等方法进行样品的观察分析. 研究表明, 多孔硅酸钙生物陶瓷植入后未见明显毒性反应、且表面沉积了一层类骨羟基磷灰石层, 说明材料具有良好的生物相容性和生物活性. 植入4周时SPECT扫描表明, CS和β-TCP的ROI值分别为53.95±15.14和9.81±3.64(p<0.01), 表明CS的血管化程度明显高于β-TCP. 植入4周时Micro-CT分析表明, CS和β-TCP的残余材料占总体积百分比分别为(16.41±1.96)%和(30.72±0.69)%(p<0.05), 组织学半定量分析也表明, CS的残余面积明显小于β-TCP(p<0.01), 说明CS的降解性明显优于β-TCP. 与β-磷酸三钙相比较, 多孔硅酸钙陶瓷材料在早期血管化、新生组织形成、材料降解性方面均具有明显优势. 研究结果显示, 多孔硅酸钙生物陶瓷有望用作硬组织修复和组织工程用支架材料.     

Bioceramics: from bone regeneration to cancer nanomedicine

Research on biomaterials has been growing in the last few years due to the clinical needs in organs and tissues replacement and regeneration. In addition, cancer nanomedicine has recently appeared as an effective means to combine nanotechnology developments towards a clinical application. Ceramic materials are suitable candidates to be used in the manufacturing of bone-like scaffolds. Bioceramic materials may also be designed to deliver biologically active substances aimed at repairing, maintaining, restoring or improving the function of organs and tissues in the organism. Several materials such as calcium phosphates, glasses and glass ceramics able to load and subsequently release in a controlled fashion drugs, hormones, growth factors, peptides or nucleic acids have been developed. In particular, to prevent post surgical infections bioceramics may be surface modified and loaded with certain antibiotics, thus preventing the formation of bacterial biofilms. Remarkably, mesoporous bioactive glasses have shown excellent characteristics as drug carrying bone regeneration materials. These bioceramics are not only osteoconductive and osteoproductive, but also osteoinductive, and have therefore been proposed as ideal components for the fabrication of scaffolds for bone tissue engineering. A recent promising development of bioceramic materials is related to the design of magnetic mediators against tumors. Magnetic composites are suitable thermoseeds for cancer treatment by hyperthermia. Moreover, magnetic nanomaterials offer a wide range of possibilities for diagnosis and therapy. These nanoparticles may be conjugated with therapeutic agents and heat the surrounding tissue under the action of alternating magnetic fields, enabling hyperthermia of cancer as an effective adjunct to chemotherapy regimens.     

A long-term evaluation of osteoinductive HA/β-TCP ceramics in vivo: 4.5 years study in pigs

It has been proved that some material-dependent calcium phosphate ceramics have intrinsic potentials to induce osteogenesis. But there is little literature concerning about the tissue response in long-term. The aim of this study is to evaluate the safety of the osteoinductive biocreamics and the stability of the newly formed bone after long-term tissue response. Porous calcium phosphate ceramics rods which contain hydroxyapatite (HA) and β-tricalcium phosphate (β-TCP) were implanted in the dorsal muscles of Banna Minipig Inbreding Line. After 4.5 years, all the implanted rods with surrounding tissues were harvested and stained with hematoxylin and eosin for histological observation. The 7 months’ rods were also harvested as short-term comparison. The histological results showed that compared with the short-term rods, amount of bone tissue formed after 4.5 years. And the newly formed bone in this bioceramics neither disappeared nor gave rise to uncontrolled growth. The bone growth in this bioceramics seemed to be self-confined. The surrounding soft tissues were normal and no tumor cell was found. We conclude that instead of disappearing or giving rise to out of control, the induced bone tissue trends to be further matured. And this bioceramics thus might have potentials in future clinical use.