软骨
组织工程
生物医学工程
材料科学
类有机物
纤维软骨
细胞生物学
硫氧化物9
解剖
鱼腥草素骨
骨膜
骨钙素
关节软骨
化学
病理
生物
医学
骨关节炎
转录因子
酶
碱性磷酸酶
替代医学
基因
生物化学
作者
Gabriella Nilsson Hall,Wai Long Tam,Konstantinos S. Andrikopoulos,Leire Casas-Fraile,George A. Voyiatzis,Liesbet Geris,Frank P. Luyten,Ioannis Papantoniou
出处
期刊:Biomaterials
[Elsevier]
日期:2021-06-01
卷期号:273: 120820-120820
被引量:40
标识
DOI:10.1016/j.biomaterials.2021.120820
摘要
Tissue engineered constructs have the potential to respond to the unmet medical need of treating deep osteochondral defects. However, current tissue engineering strategies struggle in the attempt to create patterned constructs with biologically distinct functionality. In this work, a developmentally-inspired modular approach is proposed, whereby distinct cartilaginous organoids are used as living building blocks. First, a hierarchical construct was created, composed of three layers of cartilaginous tissue intermediates derived from human periosteum-derived cells: (i) early (SOX9), (ii) mature (COL2) and (iii) (pre)hypertrophic (IHH, COLX) phenotype. Subcutaneous implantation in nude mice generated a hybrid tissue containing one mineralized and one non-mineralized part. However, the non-mineralized part was represented by a collagen type I positive fibrocartilage-like tissue. To engineer a more stable articular cartilage part, iPSC-derived cartilage microtissues (SOX9, COL2; IHH neg) were generated. Subcutaneous implantation of assembled iPSC-derived cartilage microtissues resulted in a homogenous cartilaginous tissue positive for collagen type II but negative for osteocalcin. Finally, iPSC-derived cartilage microtissues in combination with the pre-hypertrophic cartilage organoids (IHH, COLX) could form dual tissues consisting of i) a cartilaginous safranin O positive and ii) a bony osteocalcin positive region upon subcutaneous implantation, corresponding to the pre-engineered zonal pattern. The assembly of functional building blocks, as presented in this work, opens possibilities for the production of complex tissue engineered implants by embedding zone-specific functionality through the use of pre-programmed living building blocks.
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