Adipose tissue-derived progenitors for engineering osteogenic and vasculogenic grafts

The current need for bone grafts in orthopedic and reconstructive surgery cannot be satisfied by autologous tissue transplant due to its limited availability and significant associated morbidity. Tissue engineering approaches could supply sufficient amounts of bone substitutes by exploiting the ability to harvest autologous osteogenic progenitors associated with suitable porous materials. However, the generation of clinically relevant-sized constructs is critically hampered by limited vascularization, with consequent engraftment and survival only of a thin outer shell, upon in vivo implantation. To overcome this limitation, different non-mutually exclusive approaches have recently been developed to promote or accelerate graft vascularization, from angiogenic growth factor gene delivery to surgical pre-vascularization of the construct before implantation. A simple, promising strategy involves the co-culture of vasculogenic cells to form an intrinsic vascular network inside the graft in vitro, which can rapidly anastomose with the host blood vessels in vivo. Recent data have shown that adipose tissue-derived stromal vascular fraction (SVF) may provide an efficient, convenient, and autologous source for both osteogenic and endothelial cells. When SVF progenitors were cultured in appropriate bioreactor systems and ectopically implanted, a functional vascular network connected to the host was formed concomitantly to bone formation. Future studies should aim at demonstrating that this approach effectively supports survival of scaled up cell-based bone grafts at an orthotopic site. The procedure should also be adapted to become compatible with an intra-operative timeline and complemented with the definition of suitable potency markers, to facilitate its development into a simplified, reproducible, and cost-effective clinical treatment.