The effect of 3D nanofibrous scaffolds on the chondrogenesis of induced pluripotent stem cells and their application in restoration of cartilage defects.
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.
Department of Orthopaedic Surgery, Shanghai Sixth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Ji
J
Liu
Institute of Polymers, School of Materials Science and Engineering, Nanchang University, Nanchang, China.
Huarong
H
Nie
Department of Orthopaedic Surgery, Shanghai Sixth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Zhengliang
Z
Xu
Department of Orthopaedic Surgery, Shanghai Sixth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Xin
X
Niu
Department of Orthopaedic Surgery, Shanghai Sixth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Shangchun
S
Guo
Department of Orthopaedic Surgery, Shanghai Sixth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Junhui
J
Yin
Institute of Polymers, School of Materials Science and Engineering, Nanchang University, Nanchang, China.
Fei
F
Guo
Department of Orthopaedics & Traumatology, Stem Cells and Regeneration Program, School of Biomedical Sciences, Room 904, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, SAR, PR China.
Gang
G
Li
Department of Orthopaedic Surgery, Shanghai Sixth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Yang
Y
Wang
Department of Orthopaedic Surgery, Shanghai Sixth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Changqing
C
Zhang
D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry; D015153:Blotting, Western; D002356:Cartilage / Q000473:pathology*; D002454:Cell Differentiation; D049109:Cell Proliferation; D020219:Chondrogenesis; D005780:Gelatin / Q000737:chemistry; D005786:Gene Expression Regulation; D006801:Humans; D021621:Imaging, Three-Dimensional / Q000379:methods*; D007150:Immunohistochemistry; D057026:Induced Pluripotent Stem Cells / Q000166:cytology*; D051379:Mice; D008855:Microscopy, Electron, Scanning; D057139:Nanofibers / Q000737:chemistry*; D036103:Nanotechnology / Q000379:methods*; D011091:Polyesters / Q000737:chemistry; D013314:Stress, Mechanical; D023822:Tissue Engineering / Q000379:methods; D054457:Tissue Scaffolds / Q000737:chemistry; D014357:Trypsin / Q000737:chemistry; D055114:X-Ray Microtomography
D001672:Biocompatible Materials; D011091:Polyesters; C016240:polycaprolactone; D005780:Gelatin; D014357:Trypsin