Abstract:
Osteochondral defects are deep joint surface lesions that affect the articular cartilage and the underlying subchondral bone. In the current study, a tissue engineering approach encompassing individual cells encapsulated in a biocompatible hydrogel is explored in vitro and in vivo. Cell-laden hydrogels containing either human periosteum-derived progenitor cells (PDCs) or human induced pluripotent stem cell (iPSC)-derived chondrocytes encapsulated in gelatin methacryloyl (GelMA) were evaluated for their potential to regenerate the subchondral mineralized bone and the articular cartilage on the joint surface, respectively. PDCs are easily isolated and expanded progenitor cells that are capable of generating mineralized cartilage and bone tissue in vivo via endochondral ossification. iPSC-derived chondrocytes are an unlimited source of stable and highly metabolically active chondrocytes. Cell-laden hydrogel constructs were cultured for up to 28 days in a serum-free chemically defined chondrogenic medium. On day 1 and day 21 of the differentiation period, the cell-laden constructs were implanted subcutaneously in nude mice to evaluate ectopic tissue formation 4 weeks post-implantation. Taken together, the data suggest that iPSC-derived chondrocytes encapsulated in GelMA can generate hyaline cartilage-like tissue constructs with different levels of maturity, while using periosteum-derived cells in the same construct type generates mineralized tissue and cortical bone in vivo. Therefore, the aforementioned cell-laden hydrogels can be an important part of a multi-component strategy for the manufacturing of an osteochondral implant.
摘要:
骨软骨缺损是影响关节软骨和下面的软骨下骨的深层关节表面病变。在目前的研究中,在体外和体内探索了包含封装在生物相容性水凝胶中的单个细胞的组织工程方法。评估了含有人骨膜来源的祖细胞(PDC)或人诱导多能干细胞(iPSC)来源的软骨细胞的充满细胞的水凝胶在明胶甲基丙烯酰(GelMA)中的再生软骨下矿化骨和关节软骨的潜力。分别。PDC是容易分离和扩增的祖细胞,其能够通过软骨内骨化在体内产生矿化软骨和骨组织。iPSC衍生的软骨细胞是稳定且高代谢活性的软骨细胞的无限来源。将载有细胞的水凝胶构建体在无血清化学定义的软骨形成培养基中培养长达28天。在分化期的第1天和第21天,将载有细胞的构建体皮下植入裸鼠体内,以评估植入后4周的异位组织形成.一起来看,数据表明,包裹在GelMA中的iPSC衍生的软骨细胞可以生成不同成熟度的透明软骨样组织构建体,而在相同的构建体类型中使用骨膜来源的细胞在体内产生矿化组织和皮质骨。因此,上述载有细胞的水凝胶可以是制造骨软骨植入物的多组分策略的重要部分。