PurposeIn this study, we evaluated the effect of hydrogel structural properties on proliferation and biosynthesis activity of encapsulated chondrocytes.MethodsHydrogels with varying structural and mechanical properties were prepared by photopolymerizing PEGDA precursors having MWs of 3.4 kDa, 6 kDa, 10 kDa, and 20 kDa and were characterized for their swelling ratio, network structure, morphology, and mechanical properties. The effect of hydrogel structural properties on the cellular activity of encapsulated chondrocytes was studied over four weeks.ResultsVarying the molecular weight of PEGDA precursors exhibited a significant effect on the structural and mechanical properties of the hydrogels. Large mesh size was found to support cell proliferation. However, extracellular matrix (ECM) accumulation varied with the precursor molecular weight. Both PEGDA 6 kDa and 10 kDa hydrogels supported GAG accumulation, while PEGDA 10 kDa and 20KDa hydrogels supported collagen accumulation. Chondrocytes cultured in PEGDA 10 kDa hydrogels expressed a relative increase in collagen type II and aggrecan expression while maintaining low collagen type I expression.ConclusionsIncreasing mesh size of the hydrogels resulted in an increase in cellular proliferation exhibiting the strong correlation between mesh size and cell growth, while mesh size had a differential effect on ECM accumulation and expression of cartilage specific markers.Electronic Supplementary MaterialThe online version of this article (doi:10.1007/s11095-011-0378-9) contains supplementary material, which is available to authorized users.

SignificanceCell instructive biomaterial cues are a major topic of interest in both basic and applied research. In this work, we clarify how surface energy of soft biomaterials can dramatically affect mesenchymal stem cell receptor recruitment and downstream signaling related to cell fate. We elucidate how surface protein self-assembly and the resulting surface topology can act to steer mechanotransduction and related biological response of attached cells. These findings fill a critical gap in our basic understanding of cell–biomaterial interaction and highlight soft biomaterial surface energy as a dominant design factor that should not be neglected.