Dynamic stiffening of poly(ethylene glycol)-based hydrogels to direct valvular interstitial cell phenotype in a three-dimensional environment.

摘要: Abstract Valvular interstitial cells (VICs) are active regulators of valve homeostasis and disease, responsible for secreting remodeling the tissue matrix. As a result VIC activity, modulus can substantially change during development, injury repair, disease progression. While two-dimensional biomaterial substrates have been used to study mechanosensing its influence on phenotype, less is known about how these respond matrix in three-dimensional environment. Here, we synthesized MMP-degradable poly(ethylene glycol) (PEG) hydrogels with elastic moduli ranging from 0.24 kPa 12 kPa observed that cell morphology was constrained stiffer gels. To vary gel stiffness without changing morphology, cell-laden were cultured gels 3 days allow spreading, then stiffened situ via second, photoinitiated thiol-ene polymerization such increased 1.2 kPa or 13 kPa. VICs encapsulated within soft exhibited αSMA stress fibers (∼40%), hallmark myofibroblast phenotype. Interestingly, gels, became deactivated quiescent fibroblast suggesting directs phenotype independent but manner depends dimensionality culture platform. Collectively, studies present versatile method dynamic stiffening demonstrate significant effects properties environments.