Osteoblast/fibroblast coculture derived bioactive ECM with unique matrisome profile facilitates bone regeneration

Abstract

Extracellular matrix (ECM) with mimetic tissue niches was attractive to facilitate tissue regeneration <i>in situ</i> via recruitment of endogenous cells and stimulation of self-healing process. However, how to engineer the complicate tissue specific ECM with unique matrisome <i>in vitro</i> 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) <i>in vitro</i> and bone regeneration <i>in vivo</i>. 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.