title: Osteogenic potential of poly(ethylene glycol)-poly(dimethylsiloxane) hybrid hydrogels.
abstract: Growth factors have been shown to be potent mediators of osteogenesis. However, their use in tissue-engineered scaffolds not only can be costly but also can induce undesired responses in surrounding tissues. Thus, the ability to specifically induce osteogenic differentiation in the absence of exogenous growth factors through manipulation of scaffold material properties would be desirable for bone regeneration. Previous research indicates that addition of inorganic or hydrophobic components to organic, hydrophilic scaffolds can enhance multipotent stem cell (MSC) osteogenesis. However, the combined impact of scaffold inorganic content and hydrophobicity on MSC behavior has not been systematically explored, particularly in three-dimensional (3D) culture systems. The aim of the present study was therefore to examine the effects of simultaneous increases in scaffold hydrophobicity and inorganic content on MSC osteogenic fate decisions in a 3D culture environment toward the development of intrinsically osteoinductive scaffolds. Mouse 10T½ MSCs were encapsulated in a series of novel scaffolds composed of varying levels of hydrophobic, inorganic poly(dimethylsiloxane) (PDMS) and hydrophilic, organic poly(ethylene glycol) (PEG). After 21 days of culture, increased levels of osteoblast markers, runx2 and osteocalcin, were observed in scaffolds with increased PDMS content. Bone extracellular matrix (ECM) molecules, collagen I and calcium phosphate, were also elevated in formulations with higher PDMS:PEG ratios. Importantly, this osteogenic response appeared to be specific in that markers for chondrocytic, smooth muscle cell, and adipocytic lineages were not similarly affected by variations in scaffold PDMS content. As anticipated, the increase in scaffold hydrophobicity accompanying increasing PDMS levels was associated with elevated scaffold serum protein adsorption. Thus, scaffold inorganic content combined with alterations in adsorbed serum proteins may underlie the observed cell behavior.
authors.affiliation: Department of Chemical Engineering, Texas A&M University, College Station, TX 77843-3122, USA.
authors.forename: Dany J
authors.initials: DJ
authors.lastname: Munoz-Pinto
authors.forename: Andrea Carolina
authors.initials: AC
authors.lastname: Jimenez-Vergara
authors.forename: Yaping
authors.initials: Y
authors.lastname: Hou
authors.forename: Heather N
authors.initials: HN
authors.lastname: Hayenga
authors.forename: Alejandra
authors.initials: A
authors.lastname: Rivas
authors.forename: Melissa
authors.initials: M
authors.lastname: Grunlan
authors.forename: Mariah S
authors.initials: MS
authors.lastname: Hahn
mesh_terms: D000327:Adsorption / Q000187:drug effects; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001798:Blood Proteins / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D003094:Collagen / Q000378:metabolism; D004129:Dimethylpolysiloxanes / Q000737:chemistry / Q000494:pharmacology*; D055119:Elastic Modulus / Q000187:drug effects; D004549:Elastin / Q000378:metabolism; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D006025:Glycosaminoglycans / Q000378:metabolism; D020100:Hydrogels / Q000737:chemistry*; D057927:Hydrophobic and Hydrophilic Interactions / Q000187:drug effects; D008422:Materials Testing; D051379:Mice; D010012:Osteogenesis / Q000187:drug effects*; D010316:Particle Size; D010641:Phenotype; D011092:Polyethylene Glycols / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D015415:Biomarkers; D001798:Blood Proteins; D004129:Dimethylpolysiloxanes; D006025:Glycosaminoglycans; D020100:Hydrogels; D011092:Polyethylene Glycols; D003094:Collagen; D004549:Elastin; D002118:Calcium