Directed Regeneration of Osteochondral Tissue by Hierarchical Assembly of Spatially Organized Composite Spheroids. Issue 3 (21st November 2021)

• Record Type: Journal Article
• Authors: Lee, Jinkyu; Lee, Seoyun; Huh, Seung Jae; Kang, Byung‐Jae; Shin, Heungsoo
• Is Part Of: Advanced science. Volume 9:Issue 3(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-11-21
• Subjects: 3D printing -- composite spheroid -- microchamber -- osteochondral tissue regeneration -- tissue engineering; Science -- Periodicals; 505
• DOI: 10.1002/advs.202103525
• Languages: English
• ISSNs: 2198-3844

Abstract

Abstract: The use of engineered scaffolds or stem cells is investigated widely in the repair of injured musculoskeletal tissue. However, the combined regeneration of hierarchical osteochondral tissue remains a challenge due to delamination between cartilage and subchondral bone or difficulty in spatial control over differentiation of transplanted stem cells. Here, two types of composite spheroids are prepared using adipose‐derived stem cells (hADSCs) and nanofibers coated with either transforming growth factor‐ β 3 or bone morphogenetic growth factor‐2 for chondrogenesis or osteogenesis, respectively. Each type of spheroid is then cultured within a 3D‐printed microchamber in a spatially arranged manner to recapitulate the bilayer structure of osteochondral tissue. The presence of inductive factors regionally modulates in vitro chondrogenic or osteogenic differentiation of hADSCs within the biphasic construct without dedifferentiation. Furthermore, hADSCs from each spheroid proliferate and sprout and successfully connect the two layers mimicking the osteochondral interface without apertures. In vivo transplantation of the biphasic construct onto a femoral trochlear groove defect in rabbit knee joint results in 21.2 ± 2.8% subchondral bone volume/total volume and a cartilage score of 25.0 ± 3.7. The present approach can be an effective therapeutic platform to engineer complex tissue. Abstract : The spontaneously differentiated chondrogenic or osteogenic composite spheroids incorporating growth factors‐engineered fibers are spatially positioned onto each cell‐adhesive 3D printed microchamber, and the chambers are then hierarchically assembled for the biphasic construct to mimic an osteochondral tissue structure. The biphasic construct is then transplanted onto an osteochondral defect for in vivo analysis.