378113 Dual-Stage Growth Factor Release within 3D Protein-Engineered Hydrogel Niches Promotes Adipogenesis

Friday, November 21, 2014: 8:48 AM
International 7 (Marriott Marquis Atlanta)
Midori Greenwood-Goodwin1, Eric Teasley1 and Sarah C. Heilshorn2,3, (1)Bioengineering, Stanford University, Stanford, CA, (2)Materials Science and Engineering, Stanford University, Stanford, CA, (3)SLAC National Accelerator Laboratory, Stanford Institute for Materials and Energy Sciences, Menlo Park, CA

The engineering of biomimetic microenvironments from hydrogels is an emerging strategy to achieve lineage-specific differentiation in vitro. In addition to recapitulating critical matrix cues found in the native three-dimensional (3D) niche, the hydrogel can also be designed to deliver soluble factors that are present within the native inductive microenvironment. We demonstrate a versatile materials approach for the dual-stage delivery of multiple soluble factors within a 3D hydrogel to induce adipogenesis. We use a Mixing-Induced Two-Component Hydrogel (MITCH) embedded with alginate microgels to deliver two pro-adipogenic soluble factors, fibroblast growth factor 1 (FGF-1) and bone morphogenetic protein 4 (BMP-4) with two distinct delivery profiles. We show that dual-stage delivery of FGF-1 and BMP-4 to multipotent, human adipose-derived stromal cells (hADSCs) significantly increases lipid accumulation compared with the simultaneous delivery of both growth factors together. Furthermore, dual-stage growth factor delivery within a 3D hydrogel resulted in substantially more lipid accumulation compared to identical delivery profiles in 2D cultures. Gene expression analysis shows upregulation of key adipogenic markers indicative of brown-like adipocytes. These data suggest that dual-stage release of FGF-1 and BMP-4 within 3D microenvironments can promote the in vitro development of mature adipocytes with insulin sensitivity.

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