Abstract
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 α-cyclodextrins (α-CDs) threaded on a polyethylene glycol chain. The molecular mobility of PRX, α-CDs moving along the polymer, can be modulated by the number of α-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.
Highlights
As large-de ciency bone tissues are not spontaneously repaired in the human body, autologous bone,[1] allogenous bone,[2] bone prosthetic material,[3] and growth factors[4] have been used to reconstruct and regenerate bone tissues
HBMSC2.5 + HUVEC2.5 were highly stained within 3 days, suggesting that the co-culture rapidly initiated osteogenic differentiation of human bone marrow derived mesenchymal stem cells (HBMSCs), since alkaline phosphatase (ALP) is an early marker of osteoblastic differentiation
We considered three major factors involved in enhanced mineralization: (i) subcellular yesassociated protein (YAP) localization in HBMSCs induced by SPE-PRX surfaces with low mobility, (ii) crosstalk with soluble growth factors secreted from HBMSCs and human umbilical vein endothelial cells (HUVECs), and (iii) cell–cell contacts between HBMSCs and HUVECs
Summary
Functions of MSCs, osteoblastic differentiation, for bone tissue regeneration. The reduced molecular mobility of PRX surfaces was effective in improving the function of human umbilical vein endothelial cells (HUVECs).[26] RhoA and YAP activation by molecularly low mobile surfaces contributed proliferation and vascular network formation of HUVECs, which can expect promotion of angiogenesis. Based on these ndings, surfaces with low molecular mobility are expected to be suitable for both osteoblastic differentiation of MSCs and the highly angiogenic expression of HUVECs. In construction of tissue-engineered bone, angiogenesis as well as osteogenesis is essential because inadequate angiogenesis in the implanted bone tissues has a risk of tissue necrosis. We examined the gene expression levels of BMP-2, VEGF, neural (N)-cadherin, and type I collagen (COLI) via quantitative real-time polymerase chain reaction
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