College of Materials Science and Engineering, Hunan University, Changsha, China.
Shenzhen Institute, Peking University, Shenzhen, China.
J Tissue Eng Regen Med. 2021 Aug;15(8):732-744. doi: 10.1002/term.3222. Epub 2021 Jun 1.
Since chondrocyte hypertrophy greatly limits the efficiency of cartilage defects repairing via cartilage tissue engineering (CTE), it is critical to develop a functional CTE scaffold able to inhibit chondrocyte hypertrophy during this period of cartilage regeneration. In this study, we tested the applicability of using decellularized sturgeon cartilage ECM (dSCECM) scaffold to cease chondrocyte hypertrophy during cartilage damage repair. The dSCECM scaffolds with interconnected porous structure and pore size of 114.1 ± 20.9 μm were successfully prepared with freeze-dry method. Chondrocytes displayed a round shape and aggregated to form cellular spheroids within dSCECM scaffolds, which is similar to their chondrocytic phenotype within cartilage in vivo. Higher transcriptional level of chondrogenic related genes and integrin related genes was observed in chondrocytes incubated with dSCECM scaffolds instead of type I collagen (COL I) scaffolds, which were used as the control due to their widely usage in CTE and clinic applications. Furthermore, it confirmed that, compared with COL I scaffolds, dSCECM scaffolds significantly reduced the transcription of chondrocyte hypertrophy related genes in chondrocytes following the hypertrophic induction treatment. To test the ability of dSCECM scaffold to inhibit chondrocytes hypertrophy in vivo, chondrocytes with dSCECM scaffolds and COL I scaffolds were cultured with hypertrophic media and were implanted into nude mice respectively. Following 4 weeks implantation, interestingly, only the specimens derived from COL I scaffolds displayed consequences of chondrocyte hypertrophy like calcification deposition, demonstrating that chondrocyte hypertrophy is ceased by the dSCECM scaffold following hypertrophic induction. It suggests that the dSCECM scaffold can be potentially applied in clinical treating cartilage defects via the CTE approach to avoid the risk of chondrocyte hypertrophy.
由于软骨细胞肥大极大地限制了软骨组织工程（CTE）修复软骨缺损的效率，因此开发一种能够在软骨再生过程中抑制软骨细胞肥大的功能性 CTE 支架至关重要。在这项研究中，我们测试了使用脱细胞鲟鱼软骨细胞外基质（dSCECM）支架在软骨损伤修复过程中停止软骨细胞肥大的适用性。通过冷冻干燥法成功制备了具有相互连接的多孔结构和 114.1±20.9μm 孔径的 dSCECM 支架。软骨细胞在 dSCECM 支架内呈圆形，并聚集形成细胞球，这与它们在体内软骨中的软骨细胞表型相似。与 COL I 支架相比，在 dSCECM 支架中孵育的软骨细胞观察到更高的软骨相关基因和整合素相关基因的转录水平，COL I 支架被用作对照，因为它们在 CTE 和临床应用中广泛使用。此外，研究证实，与 COL I 支架相比，dSCECM 支架在经过肥大诱导处理后，显著降低了软骨细胞中软骨细胞肥大相关基因的转录。为了测试 dSCECM 支架在体内抑制软骨细胞肥大的能力，将带有 dSCECM 支架和 COL I 支架的软骨细胞分别与肥大培养基一起培养，并植入裸鼠体内。在植入 4 周后，有趣的是，只有 COL I 支架来源的标本显示出软骨细胞肥大的结果，如钙化沉积，这表明 dSCECM 支架在经过肥大诱导后可以阻止软骨细胞肥大。这表明 dSCECM 支架可以潜在地应用于 CTE 方法治疗软骨缺损，以避免软骨细胞肥大的风险。
