Injectable cell/hydrogel microspheres induce the formation of fat lobule-like microtissues and vascularized adipose tissue regeneration

In this paper, we demonstrated that collagen/alginate microspheres could be generated by a non-contact microfabrication device and serve as excellent cell embedding and delivery devices as they were porous, injectable and able to provide growth-and differentiation-supporting matrix for human adipose-derived stem cells (hASCs). The microsphere matrix demonstrated highly porous structure and mechanical stability for as long as 90 days. hASCs demonstrated high viability after microsphere formation as well as higher proliferation and more mature adipocytes induction compared to two-dimensional culture. After four weeks culture in adipogenic differentiation medium, adipocytes/collagen/alginate microspheres highly mimicking natural fat lobules were obtained and injected subcutaneously into the head of node mice. The in vivo study demonstrated vascularized adipose tissue formation in four weeks. The regenerated vasculature among the transplantation showed functional anastomosis with host vasculature, suggesting that these cell/hydrogel microspheres present injectable adipocytes delivery devices capable of generating vascularized adipose tissue in vivo and thus suitable for cell transplantation and tissue regeneration.