Das Dipankar, Bang Sumi, Zhang Shengmin, Noh Insup
Convergence Institute of Biomedical Engineering and Biomaterials, Seoul National University of Science of Technology, 232 Gongneung-ro, Nowon-gu, Seoul 01811, Korea.
Department of Chemical and Biomolecular Engineering, Seoul National University of Science of Technology, 232 Gongneung-ro, Nowon-gu, Seoul 01811, Korea.
Nanomaterials (Basel). 2017 Nov 14;7(11):389. doi: 10.3390/nano7110389.
In this article, a hybrid gel has been developed using sodium alginate (Alg) and α-tricalcium phosphate (α-TCP) particles through ionic crosslinking process for the application in bone tissue engineering. The effects of pH and composition of the gel on osteoblast cells (MC3T3) response and bioactive molecules release have been evaluated. At first, a slurry of Alg and α-TCP has been prepared using an ultrasonicator for the homogeneous distribution of α-TCP particles in the Alg network and to achieve adequate interfacial interaction between them. After that, CaCl2 solution has been added to the slurry so that ionic crosslinked gel (Alg-α-TCP) is formed. The developed hybrid gel has been physico-chemically characterized using Fourier transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM) and a swelling study. The SEM analysis depicted the presence of α-TCP micro-particles on the surface of the hybrid gel, while cross-section images signified that the α-TCP particles are fully embedded in the porous gel network. Different % swelling ratio at pH 4, 7 and 7.4 confirmed the pH responsiveness of the Alg-α-TCP gel. The hybrid gel having lower % α-TCP particles showed higher % swelling at pH 7.4. The hybrid gel demonstrated a faster release rate of bovine serum albumin (BSA), tetracycline (TCN) and dimethyloxalylglycine (DMOG) at pH 7.4 and for the grade having lower % α-TCP particles. The MC3T3 cells are viable inside the hybrid gel, while the rate of cell proliferation is higher at pH 7.4 compared to pH 7. The in vitro cytotoxicity analysis using thiazolyl blue tetrazolium bromide (MTT), bromodeoxyuridine (BrdU) and neutral red assays ascertained that the hybrid gel is non-toxic for MC3T3 cells. The experimental results implied that the non-toxic and biocompatible Alg-α-TCP hybrid gel could be used as scaffold in bone tissue engineering.
在本文中，通过离子交联工艺开发了一种使用海藻酸钠（Alg）和α-磷酸三钙（α-TCP）颗粒的混合凝胶，用于骨组织工程。评估了凝胶的pH值和组成对成骨细胞（MC3T3）反应及生物活性分子释放的影响。首先，使用超声仪制备Alg和α-TCP的浆料，以使α-TCP颗粒在Alg网络中均匀分布，并实现它们之间充分的界面相互作用。之后，将氯化钙溶液添加到浆料中，从而形成离子交联凝胶（Alg-α-TCP）。使用傅里叶变换红外（FTIR）光谱、扫描电子显微镜（SEM）和溶胀研究对所开发的混合凝胶进行了物理化学表征。SEM分析表明混合凝胶表面存在α-TCP微粒，而横截面图像表明α-TCP颗粒完全嵌入多孔凝胶网络中。在pH 4、7和7.4下不同的溶胀率证实了Alg-α-TCP凝胶的pH响应性。具有较低百分比α-TCP颗粒的混合凝胶在pH 7.4下显示出更高的溶胀率。混合凝胶在pH 7.4下以及对于具有较低百分比α-TCP颗粒的等级，显示出牛血清白蛋白（BSA）、四环素（TCN）和二甲基草酰甘氨酸（DMOG）的更快释放速率。MC3T3细胞在混合凝胶内具有活力，而与pH 7相比，在pH 7.4下细胞增殖速率更高。使用噻唑蓝四氮唑溴盐（MTT）、溴脱氧尿苷（BrdU）和中性红测定进行的体外细胞毒性分析确定该混合凝胶对MC3T3细胞无毒。实验结果表明，无毒且生物相容的Alg-α-TCP混合凝胶可作为骨组织工程中的支架。
