Electrospun silk fibroin/poly(lactide-co-ε-caprolactone) nanofibrous scaffolds for bone regeneration.
BACKGROUND
Tissue engineering has become a promising therapeutic approach for bone regeneration. Nanofibrous scaffolds have attracted great interest mainly due to their structural similarity to natural extracellular matrix (ECM). Poly(lactide-co-ε-caprolactone) (PLCL) has been successfully used in bone regeneration, but PLCL polymers are inert and lack natural cell recognition sites, and the surface of PLCL scaffold is hydrophobic. Silk fibroin (SF) is a kind of natural polymer with inherent bioactivity, and supports mesenchymal stem cell attachment, osteogenesis, and ECM deposition. Therefore, we fabricated hybrid nanofibrous scaffolds by adding different weight ratios of SF to PLCL in order to find a scaffold with improved properties for bone regeneration.


METHODS
Hybrid nanofibrous scaffolds were fabricated by blending different weight ratios of SF with PLCL. Human adipose-derived stem cells (hADSCs) were seeded on SF/PLCL nanofibrous scaffolds of various ratios for a systematic evaluation of cell adhesion, proliferation, cytotoxicity, and osteogenic differentiation; the efficacy of the composite of hADSCs and scaffolds in repairing critical-sized calvarial defects in rats was investigated.


RESULTS
The SF/PLCL (50/50) scaffold exhibited favorable tensile strength, surface roughness, and hydrophilicity, which facilitated cell adhesion and proliferation. Moreover, the SF/PLCL (50/50) scaffold promoted the osteogenic differentiation of hADSCs by elevating the expression levels of osteogenic marker genes such as BSP, Ocn, Col1A1, and OPN and enhanced ECM mineralization. In vivo assays showed that SF/PLCL (50/50) scaffold improved the repair of the critical-sized calvarial defect in rats, resulting in increased bone volume, higher trabecular number, enhanced bone mineral density, and increased new bone areas, compared with the pure PLCL scaffold.


CONCLUSIONS
The SF/PLCL (50/50) nanofibrous scaffold facilitated hADSC proliferation and osteogenic differentiation in vitro and further promoted new bone formation in vivo, suggesting that the SF/PLCL (50/50) nanofibrous scaffold holds great potential in bone tissue regeneration.
Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Donghua University, Shanghai, People's Republic of China.
Zi
Z
Wang
Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Donghua University, Shanghai, People's Republic of China.
Ming
M
Lin
Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Donghua University, Shanghai, People's Republic of China.
Qing
Q
Xie
Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Donghua University, Shanghai, People's Republic of China.
Hao
H
Sun
Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Donghua University, Shanghai, People's Republic of China.
Yazhuo
Y
Huang
Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Donghua University, Shanghai, People's Republic of China.
DanDan
D
Zhang
Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Donghua University, Shanghai, People's Republic of China.
Zhang
Z
Yu
Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Donghua University, Shanghai, People's Republic of China.
Xiaoping
X
Bi
Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Donghua University, Shanghai, People's Republic of China.
Junzhao
J
Chen
Biomaterials and Tissue Engineering Laboratory, College of Chemistry & Chemical Engineering and Biotechnology, Donghua University, Shanghai, People's Republic of China.
Jing
J
Wang
Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Donghua University, Shanghai, People's Republic of China.
Wodong
W
Shi
Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Donghua University, Shanghai, People's Republic of China.
Ping
P
Gu
Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Donghua University, Shanghai, People's Republic of China.
Xianqun
X
Fan
D000273:Adipose Tissue / Q000166:cytology; D000293:Adolescent; D000328:Adult; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D001861:Bone Regeneration / Q000502:physiology*; D002448:Cell Adhesion; D002453:Cell Cycle; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D004563:Electrochemistry; D005109:Extracellular Matrix; D005349:Fibroins / Q000737:chemistry*; D006801:Humans; D007124:Immunoenzyme Techniques; D057139:Nanofibers / Q000737:chemistry; D011091:Polyesters / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D047011:Silk / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared; D013718:Tensile Strength; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry; D055815:Young Adult
D011091:Polyesters; D011108:Polymers; D012333:RNA, Messenger; D047011:Silk; C062968:lactide-caprolactone copolymer; D005349:Fibroins
human adipose-derived mesenchymal stem cells; osteogenesis; poly(lactide-co-ε-caprolactone); proliferation; silk fibrin