Solouk Atefeh, Mirzadeh Hamid, Amanpour Saeed
Biomedical Engineering Faculty, Amirkabir University of Technology (Tehran Polytechnic), Tehran, Iran.
Polymer Engineering Faculty, Amirkabir University of Technology (Tehran Polytechnic), Tehran, Iran.
Prog Biomater. 2014;3:143-151. doi: 10.1007/s40204-014-0031-x. Epub 2014 Dec 9.
Cartilage is a tissue with limited repair capacity and also sparse population of cells entrapped within a dense extracellular matrix, therefore, delivery of the cells to site of damaged cartilage can improve its healing potential. Synthetic biomaterials such as poly (d,l-lactide-co-glycolide) (PLGA) have been used as both preformed or injectable scaffolds in tissue engineering in order to carry and keep cells in the site of injury with minimal side effects. The injectable biocompatible polymeric scaffolds can reach to effected area via minimally invasive injection without need to open the joint, less painful approach and also having possibility to fill complicated shape defects. In this study, it was hypothesized that PLGA solved in -methyl pyrrolidine (NMP) may act as a proper carrier for cell delivery to the site of the damage and also supports their growth. The results of in vitro assays including both live/dead (AO/PI) and MTT showed the majority of the cells were remained alive between 3 up to 21 days, respectively. The amount of resealed GAG from the mesenchymal stem cells (MSCs) which were in contact with both PLGA and alginate constructs (used as control) indicated that for day 7 MSCs in contact with alginate secreted more GAG (3.45 ± 0.453 µg/mL for alginate and 2.36 ± 0.422 µg/mL for PLGA matrices), but at longer times (21 days) cells in contact with PLGA elicited more GAG (6.26 ± 0.968 µg/mL for alginate and 8.47 ± 0.871 µg/mL for the PLGA matrices). Sol-gel systems comprising PLGA, NMP, and cells as well as alginate/cells were subcutaneously injected into four nude mice (each mouse had three injection sites). PLGA/NMP was solidify immediately and formed an interconnecting 3-D porous structure that allowed body fluid to penetrate through them. In vivo evaluation showed that PLGA/NMP scaffolds could support injected cells as a fibrocartilage tissue was formed after 6 months of injection. We found that PLGA/NMP system might be a proper minimally invasive therapeutics option for cartilage repair.
软骨是一种修复能力有限的组织，并且细胞被困在致密的细胞外基质中，数量稀少，因此，将细胞输送到受损软骨部位可以提高其愈合潜力。合成生物材料，如聚（d，l-丙交酯-共-乙交酯）（PLGA），已被用作组织工程中的预制或可注射支架，以便在损伤部位携带和保留细胞，且副作用最小。可注射的生物相容性聚合物支架可以通过微创注射到达受影响区域，无需打开关节，疼痛较小，并且有可能填充复杂形状的缺损。在本研究中，假设溶解在N-甲基吡咯烷（NMP）中的PLGA可能作为将细胞输送到损伤部位的合适载体，并支持细胞生长。包括活/死（AO/PI）和MTT在内的体外试验结果表明，大多数细胞在3至21天内分别保持存活。与PLGA和藻酸盐构建体（用作对照）接触的间充质干细胞（MSCs）重新封闭的糖胺聚糖（GAG）量表明，在第7天，与藻酸盐接触的MSCs分泌更多的GAG（藻酸盐为3.45±0.453μg/mL，PLGA基质为2.36±0.422μg/mL），但在更长时间（21天），与PLGA接触的细胞产生更多的GAG（藻酸盐为6.26±0.968μg/mL，PLGA基质为8.47±0.871μg/mL）。将包含PLGA、NMP和细胞以及藻酸盐/细胞的溶胶-凝胶系统皮下注射到四只裸鼠体内（每只小鼠有三个注射部位）。PLGA/NMP立即固化并形成相互连接的三维多孔结构，使体液能够渗透其中。体内评估表明，PLGA/NMP支架可以支持注射的细胞，因为注射6个月后形成了纤维软骨组织。我们发现PLGA/NMP系统可能是软骨修复的一种合适的微创治疗选择。
