Luckanagul Jittima Amie, Metavarayuth Kamolrat, Feng Sheng, Maneesaay Phudit, Clark Amy Y, Yang Xiaoming, García Andrés J, Wang Qian
Department of Chemistry and Biochemistry, University of South Carolina, 631 Sumter Street, Columbia, South Carolina 29208, United States.
Department of Food and Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Chulalongkorn University, 254 Phayathai Road, Wangmai, Pathumwan, Bangkok, Thailand 10330.
ACS Biomater Sci Eng. 2016 Apr 11;2(4):606-615. doi: 10.1021/acsbiomaterials.5b00561. Epub 2016 Mar 18.
Plant viruses have been highlighted among material research due to their well-defined structures in nanoscale, monodispersity, stability, and chemical functionalities. Each of the thousands coat protein subunits on a viral nanoparticle can be homogeneously modified, chemically and genetically, with a functional ligand leading to a high-density and spatial distribution of ligands on each particle (multivalency). Previous reports from our group have evidenced that substrates coated with Tobacco mosaic virus (TMV) and its mutant promote early osteogenesis of mesenchymal stem cells (MSCs). We then fabricated a three-dimensional (3D) biopolymeric scaffold with rod-like TMV in the form of a sponge-like hydrogel for tissue engineering purposes. The hydrogel was functionalized with the cellular recognition peptide, arginine-glycine-aspartic acid (RGD), through an incorporation of an RGD mutant of TMV (TMV-RGD). The virus-functionalized hydrogel materials were shown to aid bone differentiation of MSCs in vitro. Herein, we performed an in vivo study based on the TMV and TMV-RGD hydrogels in Sprague-Dawley rats with cranial bone defects. This report substantiated the hypothesis that TMV-functionalized hydrogel scaffolds did not cause systemic toxicity when implanted in the defect site and that the TMV-based hydrogel platform can support cell localization and can be further optimized for bone regeneration and repair.
植物病毒因其在纳米尺度上明确的结构、单分散性、稳定性和化学功能，在材料研究中备受关注。病毒纳米颗粒上数千个衣壳蛋白亚基中的每一个都可以通过化学和基因手段，用功能性配体进行均匀修饰，从而在每个颗粒上形成高密度且具有空间分布的配体（多价性）。我们团队之前的报告证明，涂有烟草花叶病毒（TMV）及其突变体的底物可促进间充质干细胞（MSC）的早期成骨。然后，我们为组织工程目的，用棒状TMV制备了一种海绵状水凝胶形式的三维（3D）生物聚合物支架。通过掺入TMV的RGD突变体（TMV-RGD），使水凝胶用细胞识别肽精氨酸-甘氨酸-天冬氨酸（RGD）进行功能化。病毒功能化的水凝胶材料在体外显示有助于MSC的骨分化。在此，我们在患有颅骨缺损的Sprague-Dawley大鼠中，基于TMV和TMV-RGD水凝胶进行了一项体内研究。本报告证实了以下假设：TMV功能化的水凝胶支架植入缺损部位时不会引起全身毒性，并且基于TMV的水凝胶平台可以支持细胞定位，并可进一步优化用于骨再生和修复。
