Personalized 3D-printed TDM/ZrO₂ scaffolds laden with iPSC-derived SOX9⁺ sclerotomal progenitors for functional osteochondral regeneration

Abstract

Osteochondral defects resulting from trauma or degenerative diseases are challenging to treat due to the complex hierarchical structure and limited self-healing capacity of articular cartilage. Recent advancements have identified SOX9-positive (SOX9+) sclerotomal progenitors (scl-progenitors), derived from human pluripotent stem cells, as a promising cell source capable of mimicking endochondral ossification and promoting osteochondral regeneration. A personalized three-dimensional (3D)-bioprinted scaffold was developed using treated dentin matrix (TDM)—a decellularized matrix rich in low-crystallinity hydroxyapatite, type I collagen, and osteoinductive factors—as the core bioactive material. To enhance mechanical strength and printability, the TDM was combined with methacrylated gelatin and zirconia nanoparticles. SOX9+ scl-progenitors were encapsulated within the hydrogel matrix and printed using extrusion-based 3D bioprinting to fabricate cell-laden scaffolds with tunable biomechanical and biological properties. The engineered constructs supported robust cell viability, proliferation, and differentiation toward osteochondral lineages in vitro. In vivo implantation in a nude rat knee osteochondral defect model demonstrated excellent biocompatibility and significant regeneration of both cartilage and subchondral bone tissue. This study presents a translatable and customizable platform integrating stem cell technology, natural biomaterials, and 3D bioprinting for osteochondral tissue engineering. The bioengineered construct offers substantial advantages for personalized osteochondral defect repair over conventional approaches.  

Keywords

Osteochondral regeneration / SOX9-positive sclerotomal progenitors / Three-dimensional bioprinting / Tissue engineering / Treated dentin matrix

Funding

This work was supported by grants from the National Nature Science Foundation of China (82270958), the Major Science and Technology Projects in Yunnan Province(202302AA310038), and West China Hospital of Stomatology, Sichuan University Interdisciplinary innovation projects with research and development projects (RD-03-202106).

Conflict of Interest

The authors declare that they have no affiliations with or involvement in any organization or entity with any financial interest in the subject matter or materials discussed in this manuscript.

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