In the process of bone regeneration, new bone formation is largely affected by physico-chemical cues in the surrounding microenvironment. Tissue cells reside in a complex scaffold physiological microenvironment. The scaffold should provide certain circumstance full of structural cues to enhance multipotent mesenchymal stem cell (MSC) differentiation, osteoblast growth, extracellular matrix (ECM) deposition, and subsequent new bone formation. This article reviewed advances in fabrication technology that enable the creation of biomaterials with well-defined pore structure and surface topography, which can be sensed by host tissue cells (esp., stem cells) and subsequently determine cell fates during differentiation. Three important cues, including scaffold pore structure (i.e., porosity and pore size), grain size, and surface topography were studied. These findings improve our understanding of how the mechanism scaffold microenvironmental cues guide bone tissue regeneration.

To accelerate bone tissue formation, scaffolds better provide stimulatory niches to the residing cells for osteogenic differentiation. In this study, polycaprolactone (PCL) nanofibers containing various amounts of chitosan (0, 3, 9, and 23%) were prepared and evaluated for their osteogenic differentiation of preosteoblasts in 2D and 3D cultures. Characterization of the obtained nanofibers revealed that average fiber diameter, hydrophilicity, Young's modulus, and fiber degradation were closely correlated with the amount of chitosan in PCL nanofibers. Incorporation of chitosan in PCL nanofibers not only improved the adhesion and proliferation of MC 3T3-E1 cells but also elevated calcium deposition, alkaline phosphatase (ALP) activity, and the expression of osteopontin (OPN) compared to PCL alone nanofibers. Culture of cell-rich 3D constructs prepared by layer-by-layer assembling MC 3T3-E1 with chitosan containing PCL nanofibers led to a uniform tissue formation with significant mineralization at 21 days. In all, chitosan containing PCL nanofibers are superior to PCL nanofibers in promoting bone tissue formation.

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