摘要
Extracellular matrix(ECM)with mimetic tissue niches was attractive to facilitate tissue regeneration in situ via recruitment of endogenous cells and stimulation of self-healing process.However,how to engineer the complicate tissue specific ECM with unique matrisome in vitro was a challenge of ECM-based biomaterials in tissue engineering and regenerative medicine.Here,we introduced coculture system to engineer bone mimetic ECM niche guided by cell-cell communication.In the cocultures,fibroblasts promoted osteogenic differentiation of osteoblasts via extracellular vesicles.The generated ECM(MN-ECM)displayed a unique appearance of morphology and biological components.The advantages of MN-ECM were demonstrated with promotion of multiple cellular behaviors(proliferation,adhesion and osteogenic mineralization)in vitro and bone regeneration in vivo.Moreover,proteomic analysis was used to clarify the molecular mechanism of MN-ECM,which revealed a specific matrisome signature.The present study provides a novel strategy to generate ECM with tissue mimetic niches via cell-cell communication in a coculture system,which forwards the development of tissue-bioactive ECM engineering along with deepening the understanding of ECM niches regulated by cells for bone tissue engineering.
基金
supported by the National Natural Science Foundation of China(Grant No.31300800 , 81702625)
the Zhejiang Province Welfare Technology Application Research Project(Grant No.2017C33135)
the Natural Science Foundation of Ningbo(Grant No.2018A610202 , 2019A610309)
the K.C.Wong Magna Fund in Ningbo University.
