Synergetic Cues of Bioactive Nanoparticles and Nanofibrous Structure in Bone Scaffolds to Stimulate Osteogenesis and Angiogenesis.

Providing a nanotopological physical cue in concert with a bioactive chemical signal within 3D scaffolds, while it being considered a promising approach for bone regeneration, has yet to be explored. Here, we develop 3D porous scaffolds that are networked to be a nanofibrous structure and incorporated with bioactive glass nanoparticles (BGn) to tackle this issue. The presence of BGn and nanofibrous structure (BGn + nanofibrous) substantially increased the surface area, hydro-affinity and protein loading capacity of scaffolds. In particular, the BGn released Si and Ca ions to the levels known to be biologically effective, offering the bone scaffold an ability to deliver therapeutic ions. The mesenchymal stem cells (MSCs) from rats exhibited significantly accelerated adhesion events including cell anchorage, cytoskeletal extensions, and the expression of adhesion signaling molecules on the BGn/nanofibrous scaffolds. The cells gained a more rapid proliferation and migration (penetration) ability over 2 weeks within the BGn + nanofibrous scaffolds than within either nanofibrous or BGn scaffolds. The osteogenesis of MSCs, as confirmed by the expressions of bone-associated genes and proteins, as well as the cellular mineralization was significantly stimulated by the BGn and nanofibrous topology in a synergistic manner. The behaviors of endothelial cells (HUVECs) including cell migration and tubule networking were also enhanced when influenced by the BGn and nanofibrous scaffolds (but more by BGn than by nanofiber). A subcutaneous tissue implantation of the scaffolds further evidenced the in vivo stimulation of neo-blood vessel formation by the BGn + nanofibrous cues, suggesting the possible promising role in bone regeneration. Taken together, the therapeutic ions and nanofibrous topology implemented within 3D scaffolds are considered to play synergistic actions in osteogenesis and angiogenesis, implying the potential usefulness of the BGn + nanofibrous scaffolds for bone tissue engineering.