In vivo cell-matrix interaction is a dynamic process that includes secretion, organization, and degradation of extracellular matrix (ECM); however, traditional in vitro tissue culture substrates are not cell-responsive and therefore inhibit dynamic cell-matrix remodeling.  Our laboratory has previously created cell-responsive hydrogels through matrix metalloproteinase (MMP)-sensitive crosslinking of hyaluronic acid (HA).  Although the MMP-sensitive hydrogels permit cellular remodeling, hydrogels lack the fibrillar, anisotropic structure of native ECM.  Consequently, it is important to develop a cell-responsive, fibrous scaffold to better mimic native ECM.  We report here on a chemical modification scheme to create MMP-sensitive and photopolymerizable HA macromers, capable of hydrogel and fibrous scaffold formation.  The hydrogel formation is selectively degraded by MMP-2 but stable in buffer over 28 days, while the fibrous scaffold formation contains submicron diameter fibers that mimic native ECM topography.  The system represents a novel synthetic ECM to study cell-matrix interactions in vitro and in vivo.

MMP-sensitive and photopolymerizable hyaluronic acid macromers to fabricate biomimetic fibrous scaffolds

244th National Meeting (2012)

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