Chemical control of FGF-2 release for promoting calvarial healing with adipose stem cells.
Chemical control of protein secretion using a small molecule approach provides a powerful tool to optimize tissue engineering strategies by regulating the spatial and temporal dimensions that are exposed to a specific protein. We placed fibroblast growth factor 2 (FGF-2) under conditional control of a small molecule and demonstrated greater than 50-fold regulation of FGF-2 release as well as tunability, reversibility, and functionality in vitro. We then applied conditional control of FGF-2 secretion to a cell-based, skeletal tissue engineering construct consisting of adipose stem cells (ASCs) on a biomimetic scaffold to promote bone formation in a murine critical-sized calvarial defect model. ASCs are an easily harvested and abundant source of postnatal multipotent cells and have previously been demonstrated to regenerate bone in critical-sized defects. These results suggest that chemically controlled FGF-2 secretion can significantly increase bone formation by ASCs in vivo. This study represents a novel approach toward refining protein delivery for tissue engineering applications.
Hagey Laboratory for Pediatric Regenerative Medicine, Stanford University School of Medicine, Stanford, California 94305, USA.
Matthew D
MD
Kwan
Mark A
MA
Sellmyer
Natalina
N
Quarto
Andrew M
AM
Ho
Thomas J
TJ
Wandless
Michael T
MT
Longaker
D017667:Adipocytes / Q000378:metabolism / Q000637:transplantation; D000818:Animals; D016222:Fibroblast Growth Factor 2 / Q000096:biosynthesis* / Q000235:genetics; D017102:Fracture Healing; D008297:Male; D051379:Mice; D008819:Mice, Nude; D012886:Skull / Q000293:injuries*; D012887:Skull Fractures / Q000628:therapy*; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000378:metabolism*; D023822:Tissue Engineering; D054457:Tissue Scaffolds; D014184:Transplantation, Homologous
D016222:Fibroblast Growth Factor 2
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