Chondroitin Sulfate-Tyramine-Based Hydrogels for Cartilage Tissue Repair.

Chondroitin Sulfate-Tyramine-Based Hydrogels for Cartilage Tissue Repair.
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DOI:
10.3390/ijms24043451
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发表时间:
2023-02-09
影响因子:
5.6
通讯作者:
--
中科院分区:
生物学2区
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软骨的退化,由于创伤,机械负荷或疾病,导致细胞外基质(ECM)完整性的大量损失和骨关节炎(OA)的发展。硫酸软骨素(CS)是高度硫酸化的糖胺聚糖(GAGs)的一员,是软骨组织ECM的主要成分。在这项研究中,我们旨在研究机械负荷对包被cs -酪胺-明胶(CS-Tyr/Gel)水凝胶的骨髓间充质干细胞(BM-MCSs)成软骨分化的影响,以评估该复合材料在体外OA软骨再生研究中的适用性。CS-Tyr/Gel/BM-MSCs复合材料在软骨外植体上表现出良好的生物整合性。施加轻微的机械负荷刺激了CS-Tyr/Gel水凝胶(免疫组织化学胶原II染色)中BM-MSCs的软骨分化。然而,较强的机械负荷对人体OA软骨外植体有负面影响,与未压缩的外植体相比,ECM成分(如软骨寡聚基质蛋白(COMP)和GAGs)的释放更高。最后,将CS-Tyr/Gel/BM-MSCs复合材料应用于OA软骨外植体顶部,减少了软骨外植体中COMP和GAGs的释放。结果表明,CS-Tyr/Gel/BM-MSCs复合材料可以保护OA软骨移植体免受外部机械刺激的损伤。因此,它可以用于研究OA软骨在机械负荷下的体外再生潜力和机制,并进一步展望其在体内的治疗应用。
The degradation of cartilage, due to trauma, mechanical load or diseases, results in abundant loss of extracellular matrix (ECM) integrity and development of osteoarthritis (OA). Chondroitin sulfate (CS) is a member of the highly sulfated glycosaminoglycans (GAGs) and a primary component of cartilage tissue ECM. In this study, we aimed to investigate the effect of mechanical load on the chondrogenic differentiation of bone marrow mesenchymal stem cells (BM-MCSs) encapsulated into CS-tyramine-gelatin (CS-Tyr/Gel) hydrogel in order to evaluate the suitability of this composite for OA cartilage regeneration studies in vitro. The CS-Tyr/Gel/BM-MSCs composite showed excellent biointegration on cartilage explants. The applied mild mechanical load stimulated the chondrogenic differentiation of BM-MSCs in CS-Tyr/Gel hydrogel (immunohistochemical collagen II staining). However, the stronger mechanical load had a negative effect on the human OA cartilage explants evaluated by the higher release of ECM components, such as the cartilage oligomeric matrix protein (COMP) and GAGs, compared to the not-compressed explants. Finally, the application of the CS-Tyr/Gel/BM-MSCs composite on the top of the OA cartilage explants decreased the release of COMP and GAGs from the cartilage explants. Data suggest that the CS-Tyr/Gel/BM-MSCs composite can protect the OA cartilage explants from the damaging effects of external mechanical stimuli. Therefore, it can be used for investigation of OA cartilage regenerative potential and mechanisms under the mechanical load in vitro with further perspectives of therapeutic application in vivo.