Premium
Rapid human‐derived iPSC osteogenesis combined with three‐dimensionally printed Ti6Al4V scaffolds for the repair of bone defects
Author(s) -
Yu Lingjia,
Yang Yong,
Zhang Bin,
Bai Xiaofeng,
Fei Qi,
Zhang Lei
Publication year - 2020
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.29788
Subject(s) - induced pluripotent stem cell , osseointegration , wnt signaling pathway , regeneration (biology) , mesenchymal stem cell , microbiology and biotechnology , chemistry , bone healing , regenerative medicine , stem cell , biomedical engineering , anatomy , signal transduction , medicine , embryonic stem cell , biology , biochemistry , implant , surgery , gene
Human‐induced pluripotent stem cells (iPSCs) are an alternative source of mesenchymal stem cells used for bone regeneration. However, the current osteogenically induced methods for iPSCs are slow and complex. We have used retinoic acid (RA) to induce osteogenic iPSCs within 10 days and assess whether a rapid differentiation could improve the osteogenic potential of the three‐dimensionally printed Ti6Al4V (3DTi) scaffolds. First, the osteogenic differentiation of iPSCs was induced with RA, and the osteogenic potential of iPSCs was evaluated using standard assays. In addition, a 5‐mm mandibular bone defect was generated in rats and was repaired with 3DTi scaffolds that were seeded with iPSC‐induced osteoblasts. The capacity of seeded scaffolds for the enhancement of bone regeneration in vivo was assessed. Finally, we tested the potential mechanisms of RA‐dependent iPSC bone induction and its effect on the Wnt/β‐catenin pathway. The results showed that iPSCs could form osteocytes within 10 days. Animal experiments confirmed that rapid osteo‐induced iPSCs could enhance the bone regeneration and osteointegration capacity of the 3DTi scaffolds. Mechanistically, RA could activate the AKT/GSK3β/β‐catenin pathway during the process of iPSCs osteogenesis. The rapid osteoinduction of iPSCs combined with 3DTi scaffolds is a safe, effective, and reproducible method for repairing mandibular bone defects.