Comparing Scaffold-Free and Fibrin-Based Adipose-Derived Stromal Cell Constructs for Adipose Tissue Engineering: An In Vitro and In Vivo Study

Success of adipose tissue engineering for soft tissue repair has been limited by insufficient adipogenic dif-ferentiation, an unfavorable host response, and insufficient vascularization. In this study, we examined how scaffold-free spheroid and fibrin-based environments impact these parameters in human adipose-derived stro-mal cell (ASC)-based adipose constructs. ASCs were differentiated in spheroids or fibrin-based constructs. After 7 days, conditioned medium was collected and spheroids/fibrin-based constructs were either harvested or implanted subcutaneously in athymic mice. Following 7 days of implantation, the number of blood vessels in fibrin-based constructs was significantly higher than in spheroids (93 ± 45 vs. 23 ± 11 vessels/mm2) and the inflammatory response to fibrin-based constructs was less severe. The reasons for these results were investi-gated further in vitro. We found that ASCs in fibrin-based constructs secreted significantly higher levels of the angiogenic factors VEGF and HGF and lower levels of the inflammatory cytokine IL-8. Furthermore, ASCs i