There is increasing evidence that the differentiation of stem cells is highly dependent on the extracellular microenvironment including various matrix proteins and growth factors that facilitate proliferation and consecutive cell differentiation [33–35]. Accordingly, numerous strategies have been employed ranging from biologically derived scaffolds such as fragmented omentum, Matrigel^TM, collagen, fibrin, polycaprolactone, gelatin, and hyaluronic acid to various synthetic scaffold materials, including poly(lactic-co-glycolic) acid (PLGA) and PLGA-polyethylene (PLGA-PEG) scaffolds, some of them designed as injectable biodegradable gels or beads for molecular delivery [34–51] (Tables 3.1 and 3.2) (Fig. 3.3). There is frequent reporting on the adipogenic properties of Matrigel, a protein mixture secreted by mouse sarcoma cells. Distributed as commercially available base membrane, this substrate has shown to be advantageous for the differentiation of adipose precursor cells when injected subcutaneously into nude mice [34, 52]. However, the main effect of Matrigel seems to be the induction of angiogenesis. Further, Matrigel has been tested for its properties for adipose tissue engineering in combination with various growth factors and membrane proteins [53–56]. Although Matrigel has proven utility compared to other scaffold materials of natural or synthetic origin, its broad application in clinical practice is problematic because of its tumor-derived xenogeneic origin [49].

The use of naturally derived scaffold materials such as placental decellular matrix and cross-linked hyaluron seeded with ASCs has shown promising effects on adipose tissue formation. Nevertheless, some investigators have noted a fibrous capsule surrounding these constructs in vivo, suggesting some degree of immunoreaction toward the scaffold material [35].

Other approaches have been based on the specific release of growth factors into the repair region. In particular, fibroblast growth factor (FGF) demonstrated a capacity to induce adipogenesis. Studies that investigated the effects of FGF-releasing microspheres or alginate microbeads reported an increase in vascular density, but varying results in the extent of adipose tissue formation [57, 58]. Recently, Uriel et al. attempted to avoid foreign body reactions in the context of wound repair by using a mixture of isolated proteins comprising mainly base membrane components such as laminin, collagen IV, nidogen, and fibronectin derived from subcutaneous adipose tissue. The application of this protein cocktail revealed adipose tissue formation that was enhanced compared to that obtained using Matrigel [49]. Although mostly minor volumes are achieved by the implementation of growth factors and matrix materials, some of these might still have potential clinical utility in scenarios requiring filler materials for low-grade tissue defect sites. On the other hand, the in vivo use of growth factors and potential foreign body materials will indeed be critically scrutinized before eventual translation into widespread clinical practice.