title: Well-aligned chitosan-based ultrafine fibers committed teno-lineage differentiation of human induced pluripotent stem cells for Achilles tendon regeneration.
abstract: Physical property of substrates such as stiffness and topography have been reported to induce mesenchymal stem cells differentiation into bone, muscle and neuron lineages. Human-induced pluripotent stem cells (hiPSCs) are a highly promising cell source for regenerative medicine. However, physical properties have not yet been reported to successfully induce pluripotent stem cells into specific lineages. This study aimed to develop a robust, stepwise topographic strategy to induce hiPSCs differentiate into teno-lineage. A novel spinning approach termed stable jet electrospinning (SJES), is utilized to fabricate continuous well-aligned ultraﬁne ﬁbers (891 ± 71 nm), which mimic the native tendon's microstructure and mechanical properties. hiPSCs are ﬁrst differentiated into MSCs on smooth plastic surface as confirmed by the differentiations into three mesenchymal lineages and expression of characteristic MSC surface markers through an EMT (Epithelial-Mesenchymal Transition) process. Subsequently, the hiPSC derived MSCs are seeded onto well-aligned fibers to differentiate into tenocyte-like cells through activating mechanic-signal pathway. The in situ tendon repair study further confirms that aligned fiber scaffold with hiPSC-MSCs had significant effect on improving the structural and mechanical properties of tendon injury repair. These findings indicate that the stepwise physical substrate change strategy can be adopted to induce hiPSCs differentiation for tendon tissue regeneration.
authors.affiliation: Center for Stem Cell and Tissue Engineering, School of Medicine, Zhejiang University, Hangzhou, 310058, China; Zhejiang Provincial Key Laboratory of Tissue Engineering and Regenerative Medicine, Hangzhou, 310058, China.
authors.forename: Can
authors.initials: C
authors.lastname: Zhang
authors.affiliation: State Key Laboratory for Modiﬁcation of Chemical Fibers and Polymer Materials, Donghua University, Shanghai, 201620, China; College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai, 201620, China.
authors.forename: Huihua
authors.initials: H
authors.lastname: Yuan
authors.affiliation: Center for Stem Cell and Tissue Engineering, School of Medicine, Zhejiang University, Hangzhou, 310058, China; Zhejiang Provincial Key Laboratory of Tissue Engineering and Regenerative Medicine, Hangzhou, 310058, China.
authors.forename: Huanhuan
authors.initials: H
authors.lastname: Liu
authors.affiliation: Center for Stem Cell and Tissue Engineering, School of Medicine, Zhejiang University, Hangzhou, 310058, China; Zhejiang Provincial Key Laboratory of Tissue Engineering and Regenerative Medicine, Hangzhou, 310058, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Chen
authors.affiliation: Center for Stem Cell and Tissue Engineering, School of Medicine, Zhejiang University, Hangzhou, 310058, China; Zhejiang Provincial Key Laboratory of Tissue Engineering and Regenerative Medicine, Hangzhou, 310058, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Lu
authors.affiliation: Center for Stem Cell and Tissue Engineering, School of Medicine, Zhejiang University, Hangzhou, 310058, China; Zhejiang Provincial Key Laboratory of Tissue Engineering and Regenerative Medicine, Hangzhou, 310058, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Zhu
authors.affiliation: Center for Stem Cell and Tissue Engineering, School of Medicine, Zhejiang University, Hangzhou, 310058, China; Zhejiang Provincial Key Laboratory of Tissue Engineering and Regenerative Medicine, Hangzhou, 310058, China.
authors.forename: Long
authors.initials: L
authors.lastname: Yang
authors.affiliation: Center for Stem Cell and Tissue Engineering, School of Medicine, Zhejiang University, Hangzhou, 310058, China; Zhejiang Provincial Key Laboratory of Tissue Engineering and Regenerative Medicine, Hangzhou, 310058, China.
authors.forename: Zi
authors.initials: Z
authors.lastname: Yin
authors.affiliation: Department of Biosystems Science & Engineering (D-BSSE), ETH-Zurich, Mattenstrasse 26, Basel, 4058, Switzerland.
authors.forename: Boon Chin
authors.initials: BC
authors.lastname: Heng
authors.affiliation: State Key Laboratory for Modiﬁcation of Chemical Fibers and Polymer Materials, Donghua University, Shanghai, 201620, China; College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai, 201620, China. Electronic address: yzzhang@dhu.edu.cn.
authors.forename: Yanzhong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Center for Stem Cell and Tissue Engineering, School of Medicine, Zhejiang University, Hangzhou, 310058, China; Zhejiang Provincial Key Laboratory of Tissue Engineering and Regenerative Medicine, Hangzhou, 310058, China; Department of Sports Medicine, School of Medicine, Zhejiang University, Hangzhou, China; State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China. Electronic address: hwoy@zju.edu.cn.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Ouyang
mesh_terms: D000125:Achilles Tendon / Q000502:physiology*; D002454:Cell Differentiation; D019070:Cell Lineage; D048271:Chitosan; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology*; D012038:Regeneration; D013499:Surface Properties; D054457:Tissue Scaffolds
chemical_list: D048271:Chitosan
keywords: Human induced pluripotent stem cells; Stepwise substrate change; Tendon differentiation; Tissue regeneration; Well-aligned chitosan ultrafine fibers