Biomimetic Nanocomposites to Control Osteogenic Differentiation of Human Mesenchymal Stem Cells

The design of biomimetic nanomaterials that can directly influence the behavior of cells and facilitate the regeneration of tissues and organs has become an active area of research. Here, the production of materials based on nano‐hydroxyapatite composites in scaffolds with nanofibrous and nanoporous topographies, designed to mimic the native bone matrix for applications in bone tissue engineering, is reported. Human mesenchymal stem cells grown on these nanocomposites are stimulated to rapidly produce bone minerals in situ, even in the absence of osteogenic supplements in the cell‐culture medium. Nanocomposites comprising type I collagen and nano‐hydroxyapatite are found to be especially efficient at inducing mineralization. When subcutaneously implanted into nude mice, this biomimetic nanocomposite is able to form a new bone matrix within only two weeks. Furthermore, when the nanocomposite is enriched with human mesenchymal stem cells before implantation, development of the bone matrix is accelerated to within one week. To the best of the authors' knowledge, this study provides the first clear in vitro and in vivo demonstration of osteoinduction controlled by the material characteristics of a biomimetic nanocomposite. This approach can potentially facilitate the translation of de novo bone‐formation technologies to the clinic. Obvious in vitro and in vivo evidences of osteoinduction using nanocomposites are demonstrated. The synergistic effects of calcium/phosphorous and nanotopography create a highly osteoinductive NF_PLLA+Col+HA composite. In in vitro cultures without soluble osteogenic supplements and in in vivo subcutaneous implantation in nude mice, significant bone formations are found.