title: Cell-mediated remodeling of biomimetic encapsulating hydrogels triggered by adipogenic differentiation of adipose stem cells.
abstract: One of the most common regenerative therapies is autologous fat grafting, which frequently suffers from unexpected volume loss. One approach is to deliver adipose stem cells encapsulated in the engineered hydrogels supportive of cell survival, differentiation, and integration after transplant. We describe an encapsulating, biomimetic poly(ethylene)-glycol hydrogel, with embedded peptides for attachment and biodegradation. Poly(ethylene)-glycol hydrogels containing an Arg-Gly-Asp attachment sequence and a matrix metalloprotease 3/10 cleavage site supported adipose stem cell survival and showed remodeling initiated by adipogenic differentiation. Arg-Gly-Asp-matrix metalloprotease 3/10 cleavage site hydrogels showed an increased number and area of lacunae or holes after adipose stem cell differentiation. Image analysis of adipose stem cells in Arg-Gly-Asp-matrix metalloprotease 3/10 cleavage site hydrogels showed larger Voronoi domains, while cell density remained unchanged. The differentiated adipocytes residing within these newly remodeled spaces express proteins and messenger RNAs indicative of adipocytic differentiation. These engineered scaffolds may provide niches for stem cell differentiation and could prove useful in soft tissue regeneration.
authors.affiliation: Center for Stem Cell Biology and Engineering, University of California, Santa Barbara, CA, USA; Neuroscience Research Institute, University of California, Santa Barbara, CA, USA; Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, CA, USA.
authors.forename: Tracy N
authors.initials: TN
authors.lastname: Clevenger
authors.affiliation: Neuroscience Research Institute, University of California, Santa Barbara, CA, USA; Center for Bio-Image Informatics, University of California, Santa Barbara, CA, USA.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Luna
authors.affiliation: Neuroscience Research Institute, University of California, Santa Barbara, CA, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Boctor
authors.affiliation: Neuroscience Research Institute, University of California, Santa Barbara, CA, USA; Center for Bio-Image Informatics, University of California, Santa Barbara, CA, USA.
authors.forename: Steven K
authors.initials: SK
authors.lastname: Fisher
authors.affiliation: Center for Stem Cell Biology and Engineering, University of California, Santa Barbara, CA, USA; Neuroscience Research Institute, University of California, Santa Barbara, CA, USA; Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, CA, USA.
authors.forename: Dennis O
authors.initials: DO
authors.lastname: Clegg
keywords: Adipose stem cells; Arg–Gly–Asp; MMP3; biodegradable; biomimetic; poly(ethylene)-glycol hydrogel; regenerative medicine