Synthesis and Characterization of Poly(Glycerol Sebacate) for Human Mesenchymal Response Studies
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Synthesis and Characterization of Poly(Glycerol Sebacate) for Human Mesenchymal Response Studies Israd H. Jaafar3, Mohamed M. Ammar1, Raymond E. Pearson1,4,5, John P. Coulter3, and Sabrina S. Jedlicka1,2,4 1 Materials Science & Engineering, 2Bioengineering Program, 3Mechanical Engineering & Mechanics, 4Center for Advanced Materials & Nanotechnology, 5Center for Polymer Science & Engineering, Lehigh Univerisity, Bethlehem PA ABSTRACT Cell fate modification is a critical step in preparing cells and tissues for implantation therapeutics. Novel materials possessing physical, mechanical, and chemical properties similar to those found in vivo provide a potential platform in building artificial microenvironments for therapeutic applications and well-defined biointerfaces for examining differentiation potential in stem cell biology. Poly(glycerol sebacate) (PGS), a novel biocompatible and biodegradable elastomer is one such material. With tunable mechanical properties in the range of common soft tissue, the material provides an invaluable alternative platform for use in cell-to-substrate interaction studies. This paper describes the tunability of PGS mechanical properties based on variations in curing temperatures (130, 140, and 165 °C). We characterized the material by examining properties that include equilibrium Young’s modulus (E), glass transition temperature (Tg), loss factor (tan δ), degree of crosslinking, cure kinetics, protein conformational changes, and molecular bonding compositions. Variations in PGS curing temperature provide differences in physical cues presented to the hMSCs, and work is underway to examine the cellular responses of these hMSCs to microstructured PGS. Ultimately, micro- and nanostructured PGS may be useful tools in the maintenance, differentiation, and control of signaling pathways in hMSCs. INTRODUCTION Biological cells are known to respond to a variety of stimuli in vitro. It is well known that substrate characteristics affecting the biointerface influence cell adhesion, proliferation, and differentiation. The interactions between cells and the various substrate parameters are mediated in part by proteins interacting with the substrate. These proteins then modulate cell fates via receptor-ligand interactions and protein conformational dynamics, resulting in cell responses that include adhesion structure and motility [1, 2], growth and apoptosis [3, 4], and differentiation [57]. Of importance to this study, human mesenchymal stem cell (hMSC) differentiation is influenced by the physical characteristics of the underlying substrate, such as matrix elasticity [57,8] and surface nanomorphology [9, 10]. A study on hMSCs cultured on polyacrylamide gels of varying matrix elasticities, mimicking that of brain, muscle, and collageneous tissue found that hMSCs respond dramatically in both morphology and lineage specification to the matrix presented [9]. Via comparison of hMSCs cultured on these varying substrate conditions, with and without nonmuscle myosin II (NMM II) inhibition, it is
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