Rapid human‐derived iPSC osteogenesis combined with three‐dimensionally printed Ti6Al4V scaffolds for the repair of bone defects

Abstract

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.

Three-Dimensional Impression of Biomaterials for Alveolar Graft: Scoping Review

“…Despite its low degradation rate, the PCL matrix is limited in terms of cellular adhesion and osteogenic differentiation, several authors [ 32 , 35 , 49 , 50 , 53 , 62 ] have suggested combining it with different polymers [ 37 ] and bioactive molecules such as rBMP-2, that promote proliferation and differentiation of mesenchymal stem cells into osteoblasts resulting in bone formation. Nonetheless, a recently published umbrella review regarding the efficiency of current approaches in regeneration of bone defects in non-syndromic patients with cleft palate concluded that rBMP2 seems to provide results similar to the iliac crest bone graft in terms of bone volume and vertical dimension [ 121 ]. Another limitation of the PCL matrix is its low hydrophilia [ 52 ], which can be amended when the matrix is combined with a hydrophilic material such as β -TCP [ 35 , 66 , 77 ] or polydopamine [ 37 ].…”

Enhanced Osteogenic Differentiation of Pluripotent Stem Cells via γ-Secretase Inhibition

“…Improving the differentiation process of pluripotent stem cells through understanding the signaling cues that control and contribute to the differentiation process to the desired cell type, in addition to the correct choice of the transplantation scaffold, can yield a successful nearby clinical therapy for a wide variety of tissue and organ defects [ 40 , 41 , 42 ].…”

Cell‐Based Therapies for Degenerative Musculoskeletal Diseases

“…They found that this process could be improved using 3Dprinted Ti6Al4V scaffolds. [140] In vivo, experiments have confirmed the ability of iPSCs to form bones. Duan et al combined enamel matrix derivatives (EMDs) with human iPSCs for periodontal tissue regeneration in nude mice.…”

“…They found that this process could be improved using 3D‐printed Ti6Al4V scaffolds. [ 140 ] In vivo, experiments have confirmed the ability of iPSCs to form bones. Duan et al.…”