FBS Colloquia No.429Laboratory of Tissue Biochemistry

Development and Characterization of an Osteochondral 
Composite Using iPSC-Derived Cartilage Tissue and Artificial Bone


Articular cartilage is an avascular tissue with limited intrinsic repair 
capacity following injury. In osteoarthritis, pathological changes 
affect both the articular cartilage and the underlying subchondral bone, 
highlighting the need for treatments that reconstruct these tissues as 
an integrated unit. Although autologous osteochondral transplantation is 
an effective treatment for osteochondral defects, it is limited by 
donor-site morbidity and the amount of tissue available for 
transplantation. Our laboratory has previously demonstrated cartilage 
repair through transplantation of human induced pluripotent stem cell 
(iPSC)-derived cartilage tissue. However, initial graft fixation and 
application to defects extending into the subchondral bone remain 
challenges.
To address these issues, we are developing an osteochondral composite 
combining human iPSC-derived cartilage tissue with a porous artificial 
bone scaffold composed of β-tricalcium phosphate (β-TCP). By controlling 
tissue volume during culture, we reduced internal cavity formation and 
confirmed tissue ingrowth into the interconnected pores of the scaffold 
while preserving cartilage-like matrix. Histological differences between 
tissues inside and outside the scaffold prompted us to compare their 
cell populations using single-cell RNA sequencing. This analysis 
revealed an increased proportion of a cell population characterized by 
the expression of genes associated with extracellular matrix remodeling 
and hypoxia and stress responses in samples containing tissue within the 
scaffold. These findings suggest that the environment within the 
scaffold may influence cell state. In this seminar, I will present the 
generation and characterization of this composite and discuss the 
remaining challenges and future directions for osteochondral 
reconstruction.