Kurian Amal George, Singh Rajendra K, Lee Jung-Hwan, Kim Hae-Won
Institute of Tissue Regeneration Engineering, Dankook University, Cheonan 31116, Republic of Korea.
Department of Nanobiomedical Science and BK21 NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan 31116, Republic of Korea.
ACS Appl Bio Mater. 2022 Mar 21;5(3):1130-1138. doi: 10.1021/acsabm.1c01189. Epub 2022 Feb 22.
Designing various transplantable biomaterials, especially nanoscale matrixes for bone regeneration, involves precise tuning of topographical features. The cellular fate on such engineered surfaces is highly influenced by many factors imparted by the surface modification (hydrophilicity, stiffness, porosity, roughness, ROS responsiveness). Herein, hybrid matrixes of gelatin methacryloyl (GelMA) decorated with uniform layers of nanoceria (nCe), called Ce@GelMA, were developed without direct incorporation of nCe into the scaffolds. The fabrication involves a simple base-mediated in situ deposition in which uniform nCe coatings were first made on GelMA hydrogels and then nCe layered GelMA scaffolds were made by cryodesiccation. In this hybrid platform, degradable GelMA biopolymer provides the porous microstructure and nCe provides the nanoscaled biointerface. The surface morphology and elemental composition of the matrixes analyzed by field emission scanning electron microscopy (FE-SEM) and energy-dispersive spectroscopy (EDS) show uniform nCe distribution. The surface nanoroughness and chemistry of the matrixes were also characterized using atomic force microscopy (AFM) and X-ray photoelectron spectroscopy (XPS). The presence of nCe on GelMA enhanced its mechanical properties as confirmed by compressive modulus analysis. Substantial bonelike nanoscale hydroxyapatite formation was observed on scaffolds after simulated body fluid (SBF) immersion, which was confirmed by SEM, X-ray diffraction (XRD), and Fourier transform infrared (FT-IR) spectroscopy. Moreover, the developed scaffolds could also be used as an antioxidant matrix owing to the reactive oxygen species (ROS) scavenging property of nCe as assessed by 3,3',5,5'-tetramethylbenzidine (TMB) assay. The enhanced proliferation and viability of rat bone marrow mesenchymal stem cells (rMSCs) on the scaffold surface after 3 days of culture ensures the biocompatibility of the proposed material. Considering all, it is proposed that the micro/nanoscaled matrix could mimic the composition and function of hard tissues and could be utilized as degradable scaffolds in engineering bones.
设计各种可移植生物材料，尤其是用于骨再生的纳米级基质，需要精确调整其拓扑特征。在这种工程化表面上，细胞命运受到表面修饰所赋予的许多因素（亲水性、硬度、孔隙率、粗糙度、活性氧反应性）的高度影响。在此，开发了一种用均匀的纳米氧化铈（nCe）层修饰的甲基丙烯酰化明胶（GelMA）混合基质，称为Ce@GelMA，其中nCe并未直接掺入支架中。制备过程涉及一种简单的碱介导原位沉积，首先在GelMA水凝胶上制备均匀的nCe涂层，然后通过冷冻干燥制备nCe层状GelMA支架。在这个混合平台中，可降解的GelMA生物聚合物提供多孔微结构，而nCe提供纳米级生物界面。通过场发射扫描电子显微镜（FE-SEM）和能量色散光谱（EDS）分析的基质表面形态和元素组成显示nCe分布均匀。还使用原子力显微镜（AFM）和X射线光电子能谱（XPS）对基质的表面纳米粗糙度和化学性质进行了表征。压缩模量分析证实，GelMA上nCe的存在增强了其机械性能。模拟体液（SBF）浸泡后，在支架上观察到大量类骨纳米级羟基磷灰石形成，这通过扫描电子显微镜（SEM）、X射线衍射（XRD）和傅里叶变换红外（FT-IR）光谱得到证实。此外，由于通过3,3',5,5'-四甲基联苯胺（TMB）测定评估的nCe的活性氧（ROS）清除特性，所开发的支架还可以用作抗氧化基质。培养3天后，大鼠骨髓间充质干细胞（rMSCs）在支架表面的增殖和活力增强，确保了所提出材料的生物相容性。综合考虑，建议这种微/纳米级基质可以模拟硬组织的组成和功能，并可以用作工程骨中的可降解支架。
