Bone biomimetic microenvironment induces osteogenic differentiation of adipose tissue-derived mesenchymal stem cells

Abstract A critical strategy for tissue engineering is to provide the signals necessary for tissue regeneration by mimicking the tissue microenvironment. In this study, we mimicked (1) the bone chemical and the physical microenvironment by fabricating a three-dimensional nanocomposite scaffold composed of biphasic calcium phosphates (BCP) coated with a nanocomposite layer of polycaprolactone (PCL) and hydroxyapatite nanoparticles (nHA) (BCP/PCL-nHA)), and (2) the bone's biological microenvironment by co-culturing with primary human osteoblasts (HOBs), and then investigated their effects on osteogenic differentiation of adipose tissue-derived stem cells (ASCs). In comparison with the ASCs cultured alone on BCP scaffolds that were coated only with PCL, early osteogenic differentiation of ASCs was induced by either seeding ASCs on BCP/PCL-nHA scaffolds or by co-culturing with HOBs; the combination of BCP/PCL-nHA scaffold and HOBs resulted in the synergistic enhancement of osteogenic gene expression. Moreover, we found that BCP/PCL-nHA scaffolds induced early osteogenic differentiation of ASCs through integrin-α2 and an extracellular signal-regulated kinase (ERK) signaling pathway. From the Clinical Editor The authors mimicked the physico-chemical environment of bone by fabricating a nanocomposite scaffold, and then co-cultured it with human osteoblasts. Demonstrated enhancement of osteogenic gene expression and early osteogenic differentiation of adipose tissue derived stem cells were found using this approach.