Biomimetic cues from poly(lactic-co-glycolic acid)/hydroxyapatite nano-fibrous scaffolds drive osteogenic commitment in human mesenchymal stem cells in the absence of osteogenic factor supplements.

Mimicking the complex hierarchical architecture of the 'osteon', the functional unit of cortical bone, from the bottom-up offers the possibility of generating mature bone tissue in tissue engineered bone substitutes. In this work, a modular 'bottom-up' approach has been developed to assemble bone niche-mimicking nanocomposite scaffolds composed of aligned electrospun nanofibers of poly(lactic-co-glycolic acid) (PLGA) encapsulating aligned rod-shape nano-sized hydroxyapatite (nHA). By encoding axial orientation of the nHA within these aligned nanocomposite fibers, significant improvements in mechanical properties, surface roughness, hydrophilicity and in vitro simulated body fluid (SBF) mineral deposition were achieved. Moreover, these hierarchical scaffolds induced robust formation of bone hydroxyapatite and osteoblastic maturation of human bone marrow-derived mesenchymal stem cells (hBMSCs) in growth media that was absent of any soluble osteogenic differentiation factors. The results of this investigation confirm that these tailored, aligned nanocomposite fibers, in the absence of media-bone inductive factors, offer the requisite biophysical and biochemical cues to hBMSCs to promote and support their differentiation into mature osteoblast cells and form early bone-like tissue in vitro.