Neo‐cartilage formation using human nondegenerate versus osteoarthritic chondrocyte‐derived cartilage organoids in a viscoelastic hydrogel

Abstract

Current regenerative cartilage therapies are associated with several drawbacks such as dedifferentiation of chondrocytes during expansion and the formation of fibrocartilage. Optimized chondrocyte expansion and tissue formation could lead to better clinical results of these therapies. In this study, a novel chondrocyte suspension expansion protocol that includes the addition of porcine notochordal cell‐derived matrix was used to self‐assemble human chondrocytes from osteoarthritic (OA) and nondegenerate (ND) origin into cartilage organoids containing collagen type II and proteoglycans. Proliferation rate and viability were similar for OA and ND chondrocytes and organoids formed had a similar histologic appearance and gene expression profile. Organoids were then encapsulated in viscoelastic alginate hydrogels to form larger tissues. Chondrocytes on the outer bounds of the organoids produced a proteoglycan‐rich matrix to bridge the space between organoids. In hydrogels containing ND organoids some collagen type I was observed between the organoids. Surrounding the bulk of organoids in the center of the gels, in both OA and ND gels a continuous tissue containing cells, proteoglycans and collagen type II had been produced. No difference was observed in sulphated glycosaminoglycan and hydroxyproline content between gels containing organoids from OA or ND origin after 28 days. It was concluded that OA chondrocytes, which can be harvested from leftover surgery tissue, perform similar to ND chondrocytes in terms of human cartilage organoid formation and matrix production in alginate gels. This opens possibilities for their potential to serve as a platform for cartilage regeneration but also as an in vitro model to study pathways, pathology, or drug development.

The Role of Biophysical Factors in Organ Development: Insights from Current Organoid Models

“…Bioengineering 2024, 11, x FOR PEER REVIEW 3 of 23 been shown to increase proliferation and morphogenesis in ex vivo models of the kidney [30], liver [31], cartilage [32], and brain [33].…”

“…In lung organoids, increased viscoelasticity promotes airway-mimetic tubular morphology [ 28 ] and may impact alveolar growth [ 29 ]. Increasing viscoelasticity in the microenvironment has been shown to increase proliferation and morphogenesis in ex vivo models of the kidney [ 30 ], liver [ 31 ], cartilage [ 32 ], and brain [ 33 ].…”

Osteochondral organoids: current advances, applications, and upcoming challenges

“…By combining different tissue organoids, such as bone or cartilage organoids in biological models, we can reduce the gap between individual cells and a whole organ, which is important for improving research outcomes [55]. Although there is myriad research about bone and cartilage organoids [56][57][58][59], we have limited sources for OC organoids. These systems require a more complex environment to grow two tissues with different compositions and structures.…”