Department of Biomedical Engineering, Faculty of Chemical Engineering, Tarbiat Modares University, Tehran, Iran.
Department of Biotechnology, Faculty of Chemical Engineering, Tarbiat Modares University, Jalal Ale Ahmad Street, P.O.Box: 14115-111, Tehran, Iran.
Stem Cell Res Ther. 2020 Jul 16;11(1):289. doi: 10.1186/s13287-020-01797-2.
Regeneration of articular cartilage poses a tremendous challenge due to its limited self-repair capability and inflammation at the damaged site. To generate the desired structures that mimic the structure of native tissue, microtissues with repeated functional units such as cell aggregates have been developed. Multicellular aggregates of mesenchymal stem cells (MSCs) can be used as microscale building blocks of cartilage due to their potential for cell-cell contact, cell proliferation, and differentiation.
Chondrogenic microtissues were developed through incorporation of kartogenin-releasing poly (lactic-co-glycolic acid) (PLGA) microparticles (KGN-MP) within the MSC aggregates. The chondrogenic potential of KGN-MP treated MSC aggregates was proven in vitro by studying the chondrogenic markers at the RNA level and histological analysis. In order to address the inflammatory responses at the defect site, the microtissues were delivered in vivo via an injectable, anti-inflammatory hydrogel that contained gelatin methacryloyl (GelMA) loaded with curcumin (Cur).
The KGN-MPs were fabricated to support MSCs during cartilage differentiation. According to real-time RT-PCR analysis, the presence of KGN in the aggregates led to the expression of cartilage markers by the MSCs. Both toluidine blue (TB) and safranin O (SO) staining demonstrated homogeneous glycosaminoglycan production throughout the KGN-MP incorporated MSC aggregates. The curcumin treatment efficiently reduced the expressions of hypertrophy markers by MSCs in vitro. The in vivo results showed that implantation of chondrogenic microtissues (KGN-MP incorporated MSC aggregates) using the curcumin loaded GelMA hydrogel resulted in cartilage tissue regeneration that had characteristic features close to the natural hyaline cartilage according to observational and histological results.
The use of this novel construct that contained chondrogenic cell blocks and curcumin is highly desired for cartilage regeneration.
由于关节软骨的自我修复能力有限，且受损部位存在炎症，因此关节软骨的再生极具挑战性。为了生成具有类似天然组织结构的理想结构，已经开发出具有重复功能单元（如细胞聚集体）的微组织。间充质干细胞（MSCs）的多细胞聚集体可用作软骨的微尺度构建块，因为它们具有细胞间接触、细胞增殖和分化的潜力。
通过将释放卡托辛的聚（乳酸-共-乙醇酸）（PLGA）微球（KGN-MP）纳入 MSC 聚集体中，开发出软骨生成微组织。通过研究 RNA 水平和组织学分析的软骨生成标志物，证明了 KGN-MP 处理的 MSC 聚集体的软骨生成潜力。为了解决缺陷部位的炎症反应，通过注射含有载姜黄素（Cur）的明胶甲基丙烯酰（GelMA）的抗炎水凝胶将微组织递送至体内。
KGN-MP 的制备是为了在软骨分化过程中支持 MSCs。根据实时 RT-PCR 分析，聚集体中存在 KGN 可导致 MSCs 表达软骨标志物。甲苯胺蓝（TB）和番红 O（SO）染色均显示 KGN-MP 纳入的 MSC 聚集体中均匀的糖胺聚糖产生。姜黄素处理可有效降低体外 MSCs 肥大标志物的表达。体内结果表明，使用载有姜黄素的 GelMA 水凝胶植入软骨生成微组织（KGN-MP 纳入的 MSC 聚集体）可导致软骨组织再生，根据观察和组织学结果，其具有接近天然透明软骨的特征。
这种包含软骨生成细胞块和姜黄素的新型构建体非常适合软骨再生。
