Material-Directed Chondrogenic Differentiation Under Mechanical Stimulation

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Smerchansky, Madeline E.
Roy, Krishnendu
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The mechanical properties of scaffolds used to encapsulate stem cells are widely known to help direct the differentiation of those stem cells down different lineages. When studying chondrogenesis, the ability of the scaffold to withstand force is important as joints are expected to bear loads after implantation. The goal of the project is to study how differing perfusion and compression conditions influence human mesenchymal stem cell (hMSC) chondrogenesis. We hypothesize that sinusoidal dynamic compressive stimuli along with perfusion bioreactor culture of hydrogel-MSC constructs will further enhance zonal cartilage differentiation. Using a C9-x CartiGen perfusion bioreactor, cyclic compression was applied to PEG-based hydrogel constructs laden with hMSCs. The constructs were subjected to dynamic compression following one week of static preculture. At week 3, they were removed from the bioreactor and histological sections were stained for collagen and sulfated glycosaminoglycans. Gene expression of collagen I, II, X, Sox 9 and aggrecan were analyzed. It was shown that the material composition had more of an effect on the differentiation of hMSCs into chondrocytes than the addition of mechanical stimulation, but that chondrogenesis can be enhanced when both material properties and mechanical stimulation are varied. While perfusion bioreactor culture coupled with sinusoidal dynamic loading provides a more accurate model of the articular cartilage environment when compared to static culture due to loading at joints. Dynamic culture can provide insight into cell and material interactions during differentiation, leading to a more biomimetic neocartilage tissue construct.
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