Synergy of molecularly mobile polyrotaxane surfaces with endothelial cell co-culture for mesenchymal stem cell mineralization

Stem cell-based bone tissue engineering is a promising strategy for the treatment of bone defects. Since regeneration of bone tissue takes a long time, promoting osteogenesis of stem cells is desired for earlier recovery from dysfunctions caused by bone defects. Here, we combined endothelial cell co-culture using the molecularly mobile sulfonated polyrotaxane (PRX) surfaces to enhance the mineralization of human bone marrow derived mesenchymal stem cells (HBMSCs). Sulfonated PRXs are composed of sulfopropyl ether-modified alpha-cyclodextrins (alpha-CDs) threaded on a polyethylene glycol chain. The molecular mobility of PRX, alpha-CDs moving along the polymer, can be modulated by the number of alpha-CDs. When osteoblastic differentiation was induced in HBMSCs and human umbilical vein endothelial cells (HUVECs), co-culture groups on sulfonated PRX surfaces with low molecular mobility showed the highest mineralization, which is about two times as high as co-culture groups on sulfonated PRX surfaces with high molecular mobility. Nuclear accumulation of yes-associated proteins in HBMSCs and cell-cell communication via cytokines or cadherin may play an important role in synergistically induced mineralization of HBMSCs.