Stojanović Zoran S, Ignjatović Nenad, Wu Victoria, Žunič Vojka, Veselinović Ljiljana, Škapin Srečo, Miljković Miroslav, Uskoković Vuk, Uskoković Dragan
Centre for Fine Particles Processing and Nanotechnologies, Institute of Technical Sciences of the Serbian Academy of Sciences and Arts, Knez Mihailova 35/4, 11000 Belgrade, Serbia.
Advanced Materials and Nanobiotechnology Laboratory, Department of Bioengineering, University of Illinois, 851 South Morgan Street, Chicago, IL 60607-7052, USA.
Mater Sci Eng C Mater Biol Appl. 2016 Nov 1;68:746-757. doi: 10.1016/j.msec.2016.06.047. Epub 2016 Jun 16.
Recent developments in bone tissue engineering have led to an increased interest in one-dimensional (1D) hydroxyapatite (HA) nano- and micro-structures such as wires, ribbons and tubes. They have been proposed for use as cell substrates, reinforcing phases in composites and carriers for biologically active substances. Here we demonstrate the synthesis of 1D HA structures using an optimized, urea-assisted, high-yield hydrothermal batch process. The one-pot process, yielding HA structures composed of bundles of ribbons and wires, was typified by the simultaneous occurrence of a multitude of intermediate reactions, failing to meet the uniformity criteria over particle morphology and size. To overcome these issues, the preparation procedure was divided to two stages: dicalcium phosphate platelets synthesized in the first step were used as a precursor for the synthesis of 1D HA in the second stage. Despite the elongated particle morphologies, both the precursor and the final product exhibited excellent biocompatibility and caused no reduction of viability when tested against osteoblastic MC3T3-E1 cells in 2D culture up to the concentration of 2.6mg/cm(2). X-ray powder diffraction combined with a range of electron microscopies and laser diffraction analyses was used to elucidate the formation mechanism and the microstructure of the final particles. The two-step synthesis involved a more direct transformation of DCP to 1D HA with the average diameter of 37nm and the aspect ratio exceeding 100:1. The comparison of crystalline domain sizes along different crystallographic directions showed no signs of significant anisotropy, while indicating that individual nanowires are ordered in bundles in the b crystallographic direction of the P63/m space group of HA. Intermediate processes, e.g., dehydration of dicalcium phosphate, are critical for the formation of 1D HA alongside other key aspects of this phase transformation, it must be investigated in more detail in the continuous design of smart HA micro- and nano-structures with advanced therapeutic potentials.
骨组织工程的最新进展引发了人们对一维(1D)羟基磷灰石(HA)纳米和微结构(如线、带和管)的兴趣日益浓厚。它们已被提议用作细胞底物、复合材料中的增强相以及生物活性物质的载体。在此,我们展示了使用优化的、尿素辅助的、高产率水热间歇法合成一维HA结构。该一锅法生成由带束和线束组成的HA结构,其特点是同时发生大量中间反应,在颗粒形态和尺寸方面未能满足均匀性标准。为克服这些问题,制备过程分为两个阶段:第一步合成的磷酸二钙血小板用作第二阶段合成一维HA的前体。尽管颗粒形态呈细长状,但前体和最终产物均表现出优异的生物相容性,在二维培养中对成骨MC3T3 - E1细胞进行测试时,浓度高达2.6mg/cm(2)时均未导致活力降低。结合一系列电子显微镜和激光衍射分析的X射线粉末衍射用于阐明最终颗粒的形成机制和微观结构。两步合成涉及磷酸二钙向平均直径为37nm且长径比超过100:1的一维HA的更直接转变。沿不同晶体学方向的晶畴尺寸比较未显示出明显各向异性的迹象,同时表明在HA的P63/m空间群的b晶体学方向上,单个纳米线成束有序排列。中间过程,例如磷酸二钙的脱水,对于一维HA的形成至关重要,同时这一相变的其他关键方面也必须在具有先进治疗潜力的智能HA微纳米结构的连续设计中进行更详细的研究。