Osteogenic and osteoclastogenic differentiation of co-cultured cells in polylactic acid-nanohydroxyapatite fiber scaffolds

The design of bone substitutes involves the creation of a microenvironment supporting molecular cross-talk between cells and scaffolds during tissue formation and remodelling. Bone remodelling processincludes the cooperation of bone-building cells and bone-resorbing cells.In this paper we developed polylactic acid (PLA) and composite PLA-nanohydroxyapatite (nHA) scaf-folds with 20 and 50 wt.% of nHA by electrospinning technique to be used in bone tissue engineering.The developed scaffolds have different fiber diameter, porosity with interconnected pores and mechan-ical properties. Taking cues from the bone environment features we investigated the differentiation ofhuman mesenchymal stem cells (hMSCs) from bone marrow in osteoblasts and the osteoclastogenesisin the developed scaffolds in homotypic and in co-culture up to 46 days.PLA and composite PLA-nHA scaffolds induced osteogenic and osteoclastogenic differentiation. Bothosteoblasts and osteoclasts displayed high expression of specific markers (osteopontin, osteocalcin,RANK, RANKL) and functions such as secretion of ALP, cathepsin K and TRAP activity on composite scaf-folds especially on PLA-nHA containing 20 wt.% of nHA. The heterotypic interactions between osteoblastsand osteoclasts co-cultured in the developed scaffolds triggered their functional differentiation andactivation.