Title | 3D printing of chemical-empowered tendon stem/progenitor cells for functional tissue repair |
Authors | Zhang, Yanjie Lei, Tingyun Tang, Chenqi Chen, Yangwu Liao, Youguo Ju, Wei Zhang, Hong Zhou, Bo Liang, Renjie Zhang, Tao Fan, Chunmei Chen, Xiaoyi Zhao, Yanyan Xie, Yuanhao Ye, Jinchun Heng, Boon Chin Chen, Xiao Hong, Yi Shen, Weiliang Yin, Zi |
Affiliation | Zhejiang Univ, Dept Orthoped Surg, Dr Li Dak Sum & Yip Yio Chin Ctr Stem Cells & Reg, Sir Run Run Shaw Hosp,Sch Med, Hangzhou, Peoples R China Zhejiang Univ, Dept Orthoped Surg, Sch Med, Affiliated Hosp 2, Hangzhou, Peoples R China Zhejiang Univ, Sch Med, Key Lab Tissue Engn & Regenerat Med Zhejiang Prov, Hangzhou, Peoples R China Peking Univ, Sch Stomatol, Beijing, Peoples R China China Orthopaed Regenerat Med CORMed, Hangzhou, Peoples R China |
Keywords | PLURIPOTENT STEM-CELLS TENO-LINEAGE DIFFERENTIATION STEPWISE DIFFERENTIATION MOUSE FIBROBLASTS SMALL MOLECULES BONE-MARROW SCAFFOLDS INHIBITOR ACETYLCHOLINE PROLIFERATION |
Issue Date | Apr-2021 |
Publisher | BIOMATERIALS |
Abstract | Tendon injuries are the leading cause of chronic debilitation to patients. Tendon stem/progenitor cells (TSPCs) are potential seed cells for tendon tissue engineering and regeneration, but TSPCs are prone to lose their distinct phenotype in vitro and specific differentiation into the tenocyte lineage is challenging. Utilizing small molecules in an ex vivo culture system may be a promising solution and can significantly improve the therapeutic applications of these cells. Here, by using an image-based, high-throughput screening platform on small molecule libraries, this study established an effective stepwise culture strategy for TSPCs application. The study formulated a cocktail of small molecules which effected proliferation, tenogenesis initiation and maturation phases, and significantly upregulated expression of various tendon-related genes and proteins in TSPCs, which were demonstrated by high-throughput PCR, ScxGFP reporter assay and immunocytochemistry. Furthermore, by combining small molecule-based culture system with 3D printing technology, we embedded living, chemicalempowered TSPCs within a biocompatible hydrogel to engineer tendon grafts, and verified their enhanced ability in promoting functional tendon repair and regeneration both in vivo and in situ. The stepwise culture system for TSPCs and construction of engineered tendon grafts can not only serve as a platform for further studies of underlying molecular mechanisms of tenogenic differentiation, but also provide a new strategy for tissue engineering and development of novel therapeutics for clinical applications. |
URI | http://hdl.handle.net/20.500.11897/612850 |
ISSN | 0142-9612 |
DOI | 10.1016/j.biomaterials.2021.120722 |
Indexed | SCI(E) |
Appears in Collections: | 口腔医院 |