The Effect of 3D Nanofibrous Scaffolds on the Chondrogenesis of Induced Pluripotent Stem Cells and Their Application in Restoration of Cartilage Defects

Abstract

The discovery of induced pluripotent stem cells (iPSCs) rendered the reprogramming of terminally differentiated cells to primary stem cells with pluripotency possible and provided potential for the regeneration and restoration of cartilage defect. Chondrogenic differentiation of iPSCs is crucial for their application in cartilage tissue engineering. In this study we investigated the effect of 3D nanofibrous scaffolds on the chondrogenesis of iPSCs and articular cartilage defect restoration. Super-hydrophilic and durable mechanic polycaprolactone (PCL)/gelatin scaffolds were fabricated using two separate electrospinning processes. The morphological structure and mechanical properties of the scaffolds were characterized. The chondrogenesis of the iPSCs in vitro and the restoration of the cartilage defect was investigated using scanning electron microscopy (SEM), the Cell Counting Kit-8 (CCK-8), histological observation, RT-qPCR, and western blot analysis. iPSCs on the scaffolds expressed higher levels of chondrogenic markers than the control group. In an animal model, cartilage defects implanted with the scaffold-cell complex exhibited an enhanced gross appearance and histological improvements, higher cartilage-specific gene expression and protein levels, as well as subchondral bone regeneration. Therefore, we showed scaffolds with a 3D nanofibrous structure enhanced the chondrogenesis of iPSCs and that iPSC-containing scaffolds improved the restoration of cartilage defects to a greater degree than did scaffolds alone in vivo.

The effect of nanofibre-based polyethersulfone (PES) scaffold on the chondrogenesis of human induced pluripotent stem cells

“…They demonstrated that topography of aligned nanofibrous could influence human BMSCs chondrogenesis by imitating ECM [44]. Liu et al showed that PCL/gelatine scaffold as nanofibrous scaffold enhanced the chondrogenesis of iPSCs in the in vitro and in vivo [45]. Shafiee et al several nanofibrous scaffolds were fabricated with electro-spinning and they showed that electro-spun constructs maintain NSP proliferation and enhance chondrogenic differentiation.…”

Biomaterials control of pluripotent stem cell fate for regenerative therapy

“…The cells were able to express higher levels of chondrogenic markers compared to the control cells, and when the constructs were implanted in vivo, the results showed higher cartilage specific gene and protein expressions as well as subchondral bone regeneration [262]. A recent approach prepared silk matrices by self-assembly of recombinant silk, and demonstrated the ability of silk matrices to allow long-term culture and the differentiation of both human iPSCs and ESCs in 3D conditions, providing a new chemically-defined and xeno-free culture system [263].…”

Commercializing Electrospun Scaffolds For Pluripotent Stem Cell-Based Tissue Engineering Applications

“…Nanofiber scaffolds have also been designed that promote the differentiation of PSCs into osteogenic lineages as a way to engineer bone tissue [73,74]. Finally, nanofiber scaffolds generated using solution electrospinning can also direct PSCs to form chondrocytes, enabling the generation of cartilage [75].…”