Bhattacharjee Arijit, Katti Dhirendra S
Department of Biological Sciences and Bioengineering, Indian Institute of Technology-Kanpur, Kanpur 208016, Uttar Pradesh, India.
ACS Biomater Sci Eng. 2019 Jan 14;5(1):114-125. doi: 10.1021/acsbiomaterials.8b00246. Epub 2018 May 24.
One of the major strategies in tissue engineering is the biomimetic scaffold-based approach that aims at providing a near-native-like environment for cells to facilitate the regeneration of damaged/lost tissue. The extracellular matrix in native articular cartilage contains aligned collagen fibrils in the superficial (parallel to the articular surface) and deep zones (perpendicular to articular surface) of the tissue. Therefore, we hypothesized that scaffolds with aligned pore architecture may offer aligned collagen deposition upon cell seeding, and as a result, may enable enhanced chondrogenesis. We tested this hypothesis by comparing gelatin scaffolds with random and aligned pore architecture for their ability to differentiate infrapatellar fat pad derived mesenchymal stromal cells (IFP-MSCs) toward the chondrogenic lineage. The fabricated scaffolds with random and aligned pore architecture were comparable in terms of pore size, degree of cross-linking, equilibrium swelling ratio, and in vitro degradation behavior. However, scaffolds with aligned pore architecture demonstrated higher compressive modulus along with cellular infiltration and alignment in comparison to the scaffolds with random pore architecture. An in vitro chondrogenesis study of IFP-MSCs seeded in the developed scaffold systems revealed that scaffolds with aligned pore architecture supported better chondrogenesis in terms of sGAG and total collagen (histology and biochemical) and cartilage specific matrix deposition (immunofluorescence). Further, scaffolds with aligned pore architecture also supported oriented deposition of cell secreted collagen. Taken together, these results suggest that scaffolds with aligned pore architecture enhance in vitro chondrogenic differentiation of IFP-MSCs as compared to scaffolds with random pore architecture and hence could be a potential design criterion in the development of scaffolds for cartilage regeneration.
组织工程学的主要策略之一是基于仿生支架的方法，其目的是为细胞提供一个近乎天然的环境，以促进受损/缺失组织的再生。天然关节软骨中的细胞外基质在组织的浅层（平行于关节表面）和深层（垂直于关节表面）含有排列整齐的胶原纤维。因此，我们推测具有排列整齐的孔结构的支架在接种细胞后可能会使胶原呈排列状沉积，从而可能增强软骨形成。我们通过比较具有随机孔结构和排列整齐孔结构的明胶支架将髌下脂肪垫来源的间充质基质细胞（IFP-MSCs）诱导分化为软骨谱系的能力，来验证这一假设。所制备的具有随机孔结构和排列整齐孔结构的支架在孔径、交联度、平衡溶胀率和体外降解行为方面具有可比性。然而，与具有随机孔结构的支架相比，具有排列整齐孔结构的支架表现出更高的压缩模量以及细胞浸润和排列。对接种在已开发的支架系统中的IFP-MSCs进行的体外软骨形成研究表明，就糖胺聚糖（sGAG）和总胶原蛋白（组织学和生物化学）以及软骨特异性基质沉积（免疫荧光）而言，具有排列整齐孔结构的支架支持更好的软骨形成。此外，具有排列整齐孔结构的支架还支持细胞分泌的胶原蛋白的定向沉积。综上所述，这些结果表明，与具有随机孔结构的支架相比，具有排列整齐孔结构的支架可增强IFP-MSCs的体外软骨形成分化，因此可能是软骨再生支架开发中的一个潜在设计标准。
