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

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.

HIFs in hypoxic regulation of the extracellular matrix:focus on little-known player HIF-3

The structural and associated molecules of the extracellular matrix(ECM)complex is an important component of the local milieu of cells,both for maintaining their functions and homeostasis.It is a dynamic structure that is finely tuned to changes in the microenvironment.One of these factors is hypoxia,which can arise in tissues due to physiological or pathological effects.As a result of the hypoxic effect,the properties of the ECM are significantly modified,stiffness increases,the balance between degradation and synthesis of structural proteins shifts,and the deposition of biologically active mediators’changes.Hypoxia-inducible factors(HIFs)contribute significantly to the modification of the properties of the ECM under hypoxia.Among the three HIF isoforms,HIF-1 is the most studied,with numerous identified target genes encoding proteins that participate in all matrisome compartments.Much less is known about HIF-2 and HIF-3.In the context of the effects of hypoxia on the matrisome,HIF-3 isoform is of particular interest.Unlike the first two isoforms,transiently expressed during the first hours of hypoxia,HIF-3 is activated after around 24 h of exposure to hypoxia and persists for a longer period.In addition,its transcription is more pronounced under hypoxia than are HIFs 1 and 2.HIF-3,rather than the first two isoforms,is possibly responsible for the changes that occur in matrisome during prolonged hypoxic conditions.This review attempts to summarize the available data on the involvement of HIF-3 in the matrisome modification under hypoxia.

Role of the extracellular matrix in skin aging and dedicated treatment - State of the art

The extracellular matrix(ECM)occupies the space between cell and cell,and serves as a sort of intranet which connects the whole organism.Current research is focused on the ECM and,it is now possible to develop increasingly effective strategies for the prevention and treatment of degenerative diseases and even,cutaneous ageing.In fact,the most advanced anti-aging treatments are those that regenerate the ECM,which is now regarded as the main player in the physical support of,and exchange with and between cells of nutrients,cellular mediators and growth factors.