title: Sustained presentation of BMP-2 enhances osteogenic differentiation of human adipose-derived stem cells in gelatin hydrogels.
abstract: Human adipose-derived stem cells (hASCs) show great potential for healing bone defects. Bone morphogenetic protein-2 (BMP-2) has been reported to stimulate their osteogenic differentiation both in vitro and in vivo. Here, methacrylated gelatin (GelMA) hydrogels were evaluated as a system to deliver BMP-2 to encapsulated hASCs from two different donors, and BMP-2 delivered from the hydrogels was compared to BMP-2 presented exogenously in culture media. GelMA hydrogels were shown to provide sustained, localized presentation of BMP-2 due to electrostatic interactions between the growth factor and biomaterial after an initial burst release. Both donors exhibited similar responses to the loaded and exogenous growth factor; BMP-2 from the hydrogels had a statistically significant effect on hASC osteogenic differentiation compared to exogenous BMP-2. Expression of alkaline phosphatase was accelerated, and cells in hydrogels with loaded BMP-2 deposited more calcium at one, two, and four weeks than cells without BMP-2 or with the growth factor presented in the media. There were no statistically significant differences in calcium content between groups with 25, 50, or 100 µg/mL loaded BMP-2, suggesting that using a lower growth factor dose may be as effective as a higher loading amount in this system. Taken together, these findings suggest that controlled delivery of BMP-2 from the GelMA enhances its osteogenic bioactivity compared to free growth factor presented in the media. Thus, the GelMA system is a promising biomaterial for BMP-2-mediated hASC osteogenesis. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1387-1397, 2016.
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, Ohio, 44106.
authors.forename: Julia E
authors.initials: JE
authors.lastname: Samorezov
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, Ohio, 44106.
authors.forename: Emma B
authors.initials: EB
authors.lastname: Headley
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, Ohio, 44106.
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Everett
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, Ohio, 44106.|Department of Orthopaedic Surgery, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, Ohio, 44106.|National Center for Regenerative Medicine, Division of General Medical Sciences, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, Ohio, 44106.
authors.forename: Eben
authors.initials: E
authors.lastname: Alsberg
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000469:Alkaline Phosphatase / Q000378:metabolism; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology*; D002118:Calcium / Q000032:analysis; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000032:analysis; D005780:Gelatin / Q000494:pharmacology*; D006801:Humans; D020100:Hydrogels / Q000494:pharmacology*; D010012:Osteogenesis / Q000187:drug effects*; D011994:Recombinant Proteins / Q000494:pharmacology; D013194:Staining and Labeling; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
chemical_list: D055396:Bone Morphogenetic Protein 2; D020100:Hydrogels; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2; D005780:Gelatin; D004247:DNA; D000469:Alkaline Phosphatase; D002118:Calcium
keywords: biomaterials; bone tissue engineering; drug delivery; gelatin methacrylate; growth factor
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