Meng Fangang, Yang Zibo, Long Dianbo, Gu Minghui, Shang Mei, Zeng Anyu, Wen Xingzhao, Xue Yueran, Zhao Xiaoyi, He Aishan
Department of Joint Surgery/Sports Medicine, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
Department of Orthopedics, Guangdong Provincial Key Laboratory of Orthopedics and Traumatology, Guangzhou, China.
J Biomed Mater Res A. 2022 Apr;110(4):838-850. doi: 10.1002/jbm.a.37332. Epub 2021 Dec 2.
Hyaluronan (HA) provides a favorable environment for chondrogenesis of bone marrow mesenchymal stem cells (BMSCs). A previous report from our group indicated that addition of HA increases the chondro-inductive capacity of scaffolds. Therefore, this study aimed to investigate whether the Mw of the HA could affect chondrogenesis of BMSCs seeded on TCP-COL-HA scaffolds. Human BMSCs (hBMSCs) and rabbit BMSCs (rBMSCs) were isolated and expanded. TCP-COL scaffolds and TCP-COL-HA scaffolds with two different HA Mws were assessed for their capacity to induce cartilage regeneration from hBMSCs in vitro and in vivo. The results showed that about 96.96% of hBMSCs expressed CD44. Moreover, Hyal-1 and chondrogenic marker genes expressions were increased in hMSCs seeded on TCP-COL-HA scaffolds, and blocking the HA-CD44 interaction with an anti-CD44 antibody reduced the expression levels of Hyal-1 and chondrogenic marker genes. Additionally, TCP-COL-HA scaffolds with 2000 kDa Mw showed greater induction of BMSC chondrogenesis induction compared with those with 80 kDa Mw. Similar results were observed in an ectopic implantation nude mouse model. In a rabbit osteochondral defect repair model, rBMSCs seeded on TCP-COL-HA scaffolds with 2000 kDa Mw showed greater cartilage regeneration than those seeded with 80 kDa Mw. In addition, hBMSC-seeded TCP-COL-HA scaffolds with 2000 kDa Mw showed a significantly higher mechanical strength than those with 80 kDa Mw. Collectively, these results indicate that the Mw of HA could affect chondrogenesis of BMSCs seeded on TCP-COL-HA scaffolds. The TCP-COL-HA scaffolds might be used as allogenic off the shelf products in cartilage tissue engineering in future.
透明质酸（HA）为骨髓间充质干细胞（BMSC）的软骨形成提供了有利环境。我们团队之前的一份报告表明，添加HA可提高支架的软骨诱导能力。因此，本研究旨在探讨HA的分子量（Mw）是否会影响接种于TCP-COL-HA支架上的BMSC的软骨形成。分离并扩增人BMSC（hBMSC）和兔BMSC（rBMSC）。评估了具有两种不同HA Mw的TCP-COL支架和TCP-COL-HA支架在体外和体内诱导hBMSC软骨再生的能力。结果显示，约96.96%的hBMSC表达CD44。此外，接种于TCP-COL-HA支架上的hMSC中Hyal-1和软骨形成标记基因的表达增加，用抗CD44抗体阻断HA-CD44相互作用可降低Hyal-1和软骨形成标记基因的表达水平。此外，与80 kDa Mw的TCP-COL-HA支架相比，2000 kDa Mw的TCP-COL-HA支架对BMSC软骨形成诱导作用更强。在异位植入裸鼠模型中观察到了类似结果。在兔骨软骨缺损修复模型中，接种于2000 kDa Mw的TCP-COL-HA支架上的rBMSC比接种于80 kDa Mw的rBMSC表现出更强的软骨再生能力。此外，接种hBMSC的2000 kDa Mw的TCP-COL-HA支架的机械强度明显高于80 kDa Mw的支架。总体而言，这些结果表明HA的Mw会影响接种于TCP-COL-HA支架上的BMSC的软骨形成。TCP-COL-HA支架未来可能会作为同种异体即用型产品用于软骨组织工程。
