[en] 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.
Disciplines :
Engineering, computing & technology: Multidisciplinary, general & others
Author, co-author :
Hall, Gabriella Nilsson; Prometheus Division of Skeletal Tissue Engineering, KU Leuven, O&N1, Herestraat
Tam, Wai Long; Skeletal Biology and Engineering Research Center, Department of Development and
Andrikopoulos, Konstantinos S; Institute of Chemical Engineering Sciences, Foundation for Research and
Casas-Fraile, Leire; Laboratory of Tissue Homeostasis and Disease, Skeletal Biology and Engineering
Voyiatzis, George A; Institute of Chemical Engineering Sciences, Foundation for Research and
Geris, Liesbet ; Université de Liège - ULiège > GIGA > GIGA In silico medecine - Biomechanics Research Unit ; Prometheus Division of Skeletal Tissue Engineering, KU Leuven, O&N1, Herestraat
Luyten, Frank P; Prometheus Division of Skeletal Tissue Engineering, KU Leuven, O&N1, Herestraat
Papantoniou, Ioannis; Prometheus Division of Skeletal Tissue Engineering, KU Leuven, O&N1, Herestraat
Language :
English
Title :
Patterned, organoid-based cartilaginous implants exhibit zone specific functionality forming osteochondral-like tissues in vivo.
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