Center for Drug Delivery System, Shanghai Institute of Materia Medica, Chinese Academy of Sciences , Shanghai 201210, China.
Department of Biomaterials, Field of Tissue Engineering, Institute for Frontier Medical Sciences, Kyoto University , Kyoto 606-8507, Japan.
ACS Appl Mater Interfaces. 2017 Feb 1;9(4):3330-3342. doi: 10.1021/acsami.6b12829. Epub 2017 Jan 18.
Spinal cord injury (SCI) is one of the most devastating injuries. Treatment strategies for SCI are required to overcome comprehensive issues. Implantation of biomaterial scaffolds and stem cells has been demonstrated to be a promising strategy. However, a comprehensive recovery effect is difficult to achieve. In the comprehensive treatment process, the specific roles of the implanted scaffolds and of stem cells in combined strategy are usually neglected. In this study, a peptide-modified scaffold is developed based on hyaluronic acid and an adhesive peptide PPFLMLLKGSTR. Synchrotron radiation micro computed tomography measurement provides insights to the three-dimensional inner topographical property and perspective porous structure of the scaffold. The modified scaffold significantly improves cellular survival and adhesive growth of mesenchymal stem cells during 3D culture in vitro. After implantation in transected spinal cord, the modified scaffold and mesenchymal stems are found to function in synergy to restore injured spinal cord tissue, with respective strengths. Hindlimb motor function scores exhibit the most significant impact of the composite implant at 2 weeks post injury, which is the time secondary injury factors begin to take hold. Investigation on the secondary injury factors including inflammatory response and astrocyte overactivity at 10 days post injury reveals the possible underlying reason. Implants of the scaffold, cells, and especially the combination of both elicit inhibitory effects on these adverse factors. The study develops a promising implant for spinal cord tissue engineering and reveals the roles of the scaffold and stem cells. More importantly, the results provide the first understanding of the bioactive peptide PPFLMLLKGSTR concerning its functions on mesenchymal stem cells and spinal cord tissue restoration.
脊髓损伤 (SCI) 是最具破坏性的损伤之一。需要治疗策略来克服 SCI 的综合问题。生物材料支架和干细胞的植入已被证明是一种有前途的策略。然而，很难实现全面的恢复效果。在综合治疗过程中，通常忽略了植入支架和联合策略中干细胞的具体作用。在这项研究中，基于透明质酸和粘附肽 PPFLMLLKGSTR 开发了一种肽修饰的支架。同步辐射微计算机断层扫描测量提供了对支架三维内部形貌和透视多孔结构的见解。修饰后的支架在体外 3D 培养中显著提高了间充质干细胞的细胞存活率和粘附生长。在脊髓横断后植入时，修饰后的支架和间充质干细胞协同作用以恢复损伤的脊髓组织，各自发挥优势。损伤后 2 周，后肢运动功能评分显示复合植入物的影响最为显著，此时继发损伤因素开始起作用。对损伤后 10 天的继发损伤因素（包括炎症反应和星形胶质细胞过度活跃）的研究揭示了可能的潜在原因。支架、细胞的植入物，尤其是两者的组合，对这些不利因素都有抑制作用。该研究开发了一种有前途的脊髓组织工程植入物，并揭示了支架和干细胞的作用。更重要的是，结果首次了解了生物活性肽 PPFLMLLKGSTR 对间充质干细胞和脊髓组织修复的作用。
