Institute of Pathological Physiology, 1st Faculty of Medicine, Charles University, U nemocnice 5, Prague, 128 53, Czech Republic.
Biomedical Centre, Faculty of Medicine in Pilsen, Charles University, Alej Svobody 1655/76, Pilsen, 323 00, Czech Republic.
Mol Biol Rep. 2019 Aug;46(4):4483-4500. doi: 10.1007/s11033-019-04903-7. Epub 2019 Jun 10.
One of the main aims of bone tissue engineering, regenerative medicine and cell therapy is development of an optimal artificial environment (scaffold) that can trigger a favorable response within the host tissue, it is well colonized by resident cells of organism and ideally, it can be in vitro pre-colonized by cells of interest to intensify the process of tissue regeneration. The aim of this study was to develop an effective tool for regenerative medicine, which combines the optimal bone-like scaffold and colonization technique suitable for cell application. Accordingly, this study includes material (physical, chemical and structural) and in vitro biological evaluation of scaffolds prior to in vivo study. Thus, porosity, permeability or elasticity of two types of bone-like scaffolds differing in the ratio of collagen type I and natural calcium phosphate nanoparticles (bCaP) were determined, then analyzes of scaffold interaction with mesenchymal stem cells (MSCs) were performed. Simultaneously, dynamic seeding using a perfusion bioreactor followed by static cultivation was compared with standard static cultivation for the whole period of cultivation. In summary, cell colonization ability was estimated by determination of cell distribution within the scaffold (number, depth and homogeneity), matrix metalloproteinase activity and gene expression analysis of signaling molecules and differentiation markers. Results showed, the used dynamic colonization technique together with the newly-developed collagen-based scaffold with high content of bCaP to be an effective combined tool for producing bone grafts for bone implantology and regenerative medicine.
骨组织工程、再生医学和细胞治疗的主要目标之一是开发一种最佳的人工环境(支架),该环境可以在宿主组织内引发有利的反应,被机体常驻细胞良好定植,并且理想情况下,可以通过体外预定植目标细胞来增强组织再生过程。本研究旨在开发一种有效的再生医学工具,该工具将最佳的类骨支架与适合细胞应用的定植技术相结合。因此,本研究在体内研究之前包括支架的材料(物理、化学和结构)和体外生物学评估。因此,确定了两种胶原 I 和天然钙磷纳米颗粒(bCaP)比例不同的类骨支架的孔隙率、渗透性或弹性,然后分析了支架与间充质干细胞(MSCs)的相互作用。同时,使用灌注生物反应器进行动态接种,然后进行静态培养,与整个培养期间的标准静态培养进行了比较。总之,通过确定支架内细胞的分布(数量、深度和均匀性)、基质金属蛋白酶活性以及信号分子和分化标志物的基因表达分析来评估细胞定植能力。结果表明,使用新开发的高 bCaP 含量的基于胶原的支架与动态定植技术相结合,是一种用于生产骨植入物和再生医学用骨移植物的有效组合工具。