Li Teng, Liu Jie, Bin Fan-Chun, Duan Qi, Wu Xin-Yi, Dong Xian-Zi, Zheng Mei-Ling
Laboratory of Organic NanoPhotonics and CAS Key Laboratory of Bio-Inspired Materials and Interfacial Science, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, No.29 Zhongguancun East Road, Beijing 100190, PR China.
School of Future Technologies University of Chinese Academy of Sciences, Yanqihu Campus, Beijing 101407, PR China.
ACS Appl Bio Mater. 2024 Apr 15;7(4):2594-2603. doi: 10.1021/acsabm.4c00253. Epub 2024 Mar 24.
Repairing articular cartilage damage is challenging due to its low regenerative capacity. In vitro, cartilage regeneration is a potential strategy for the functional reconstruction of cartilage defects. A hydrogel is an advanced material for mimicking the extracellular matrix (ECM) due to its hydrophilicity and biocompatibility, which is known as an ideal scaffold for cartilage regeneration. However, chondrocyte culture in vitro tends to dedifferentiate, leading to fibrosis and reduced mechanical properties of the newly formed cartilage tissue. Therefore, it is necessary to understand the mechanism of modulating the chondrocytes' morphology. In this study, we synthesize photo-cross-linkable bovine serum albumin-glycidyl methacrylate (BSA-GMA) with 65% methacrylation. The scaffolds are found to be suitable for chondrocyte growth, which are fabricated by homemade femtosecond laser maskless optical projection lithography (FL-MOPL). The large-area chondrocyte scaffolds have holes with interior angles of triangle (T), quadrilateral (Q), pentagon (P), hexagonal (H), and round (R). The FL-MOPL polymerization mechanism, swelling, degradation, and biocompatibility of the BSA-GMA hydrogel have been investigated. Furthermore, cytoskeleton and nucleus staining reveals that the R-scaffold with larger interior angle is more effective in maintaining chondrocyte morphology and preventing dedifferentiation. The scaffold's ability to maintain the chondrocytes' morphology improves as its shape matches that of the chondrocytes. These results suggest that the BSA-GMA scaffold is a suitable candidate for preventing chondrocyte differentiation and supporting cartilage tissue repair and regeneration. The proposed method for chondrocyte in vitro culture by developing biocompatible materials and flexible fabrication techniques would broaden the potential application of chondrocyte transplants as a viable treatment for cartilage-related diseases.
修复关节软骨损伤具有挑战性，因为其再生能力较低。在体外，软骨再生是软骨缺损功能重建的一种潜在策略。水凝胶因其亲水性和生物相容性，是一种用于模拟细胞外基质（ECM）的先进材料，被认为是软骨再生的理想支架。然而，软骨细胞在体外培养时容易去分化，导致纤维化并降低新形成的软骨组织的机械性能。因此，有必要了解调节软骨细胞形态的机制。在本研究中，我们合成了甲基丙烯酸酯化率为65%的可光交联牛血清白蛋白-甲基丙烯酸缩水甘油酯（BSA-GMA）。通过自制的飞秒激光无掩膜光学投影光刻（FL-MOPL）制备的支架被发现适合软骨细胞生长。大面积软骨细胞支架具有内角为三角形（T）、四边形（Q）、五边形（P）、六边形（H）和圆形（R）的孔。研究了BSA-GMA水凝胶的FL-MOPL聚合机制、溶胀、降解和生物相容性。此外，细胞骨架和细胞核染色显示，内角较大的R支架在维持软骨细胞形态和防止去分化方面更有效。随着支架形状与软骨细胞形状匹配，其维持软骨细胞形态的能力提高。这些结果表明，BSA-GMA支架是防止软骨细胞分化以及支持软骨组织修复和再生的合适候选材料。通过开发生物相容性材料和灵活的制造技术来进行软骨细胞体外培养的方法，将拓宽软骨细胞移植作为软骨相关疾病可行治疗方法的潜在应用。
