Diana M. Yoon, Department of Chemical and Biomolecular Engineering, University of Maryland, 2113 Chemical & Nuclear Engineering Bldg., College Park, MD 20742-2111 and John P. Fisher, Fischell Department of Bioengineering, University of Maryland, 3238 Jeong H. Kim Building, College Park, MD 20742-2111.
Articular chondrocytes express type II collagen, a phenotypic extracellular matrix marker, and insulin-like growth-factor (IGF-1), a paracrine signaling molecule shown to increase cartilage matrix synthesis. While chondrocytes may be encapsulated in a degradable hydrogel to create an implantable tissue engineered construct, there is limited knowledge on how encapsulation effects both IGF-1 expression and signal transduction. Therefore, we have chosen to investigate chondrocyte paracrine signaling in hydrogel biomaterials. Preliminary studies from our laboratory have shown that chondrocytes encapsulated in alginate hydrogels express IGF-1. Furthermore, results have demonstrated that decreasing the signaling distance of chondrocytes, by increasing encapsulated chondrocyte density, results in increased IGF-1 expression. Finally, this increased IGF-1 expression was associated with an upregulation of type II collagen synthesis, indicating that construct properties may be utilized to control signal expression and therefore cell phenotype. Building on these preliminary results, we have recently begun investigating the effects of a synthetic environment, fabricated from a hydrolytically degradable polymer, on IGF-1 signaling among a chondrocyte population. The engineered construct that will be utilized in these experiments is a hydrogel formed from photocrosslinking 5-ethyl-5-(hydroxymethyl-β,β-dimethyl-1,3-dioxane-2-ethanol diacrylate (EHD) and poly(ethylene glycol) diacrylate by using the photoinitiator, 1-[4-2(hydroxyethoxy)-phenyl]-2-hydroxy-2-methyl-1-propane-1-one. This study examines the effect of chondrocyte density within EHD hydrogels on IGF-1 expression and chondrocyte phenotype, as measured by type II collagen synthesis, using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) studies. Further augmentation of hydrogel properties, including the incorporation of cell adhesion moieties, will also be examined. The results of this work will elucidate how synthetic environments augment IGF-1 signaling among chondrocytes.