Dynamic stiffening of poly(ethylene glycol)-based hydrogels to direct valvular interstitial cell phenotype in a three-dimensional environment.
Dynamic stiffening of poly(ethylene glycol)-based hydrogels to direct valvular interstitial cell phenotype in a three-dimensional environment.
复制标题
DOI：
10.1016/j.biomaterials.2015.01.047
复制
发表时间：
2015-05
期刊：
影响因子：
14
通讯作者：
Anseth, Kristi S.
中科院分区：
文献类型：
--
作者：
Mabry, Kelly M.;Lawrence, Rosa L.;Anseth, Kristi S.
瓣膜间质细胞（VICs）是瓣膜稳态和疾病的积极调节因子，负责瓣膜组织基质的分泌和重塑。由于VIC活性，瓣膜模量在发育、损伤和修复以及疾病进展过程中会发生实质性变化。虽然二维生物材料基质已被用于研究机械传感及其对VIC表型的影响，但对这些细胞在三维环境中如何响应基质模量知之甚少。在这里，我们合成了弹性模量从0.24 kPa到12 kPa的mmp可降解聚乙二醇（PEG）水凝胶，并观察到细胞形态在更硬的凝胶中受到限制。为了在不显著改变细胞形态的情况下改变凝胶刚度，将载细胞的水凝胶在0.24 kPa的凝胶中培养3天，使VIC扩散，然后通过第二次光引发的硫醇烯聚合使凝胶模量从0.24 kPa增加到1.2 kPa或13 kPa。包裹在软凝胶中的vic表现出αSMA应力纤维（约40%），这是肌成纤维细胞表型的标志。有趣的是，在硬化的凝胶中，VIC失活为静止的成纤维细胞表型，这表明基质刚度指导VIC表型独立于形态学，但在某种程度上取决于培养平台的维度。总的来说，这些研究为水凝胶的动态硬化提供了一种通用的方法，并证明了在三维环境中基质模量对VIC肌成纤维细胞特性的显著影响。
Valvular interstitial cells (VICs) are active regulators of valve homeostasis and disease, responsible for secreting and remodeling the valve tissue matrix. As a result of VIC activity, the valve modulus can substantially change during development, injury and repair, and disease progression. While two-dimensional biomaterial substrates have been used to study mechanosensing and its influence on VIC phenotype, less is known about how these cells respond to matrix modulus in a three-dimensional environment. Here, we synthesized MMP-degradable poly(ethylene glycol) (PEG) hydrogels with elastic moduli ranging from 0.24 kPa to 12 kPa and observed that cell morphology was constrained in stiffer gels. To vary gel stiffness without substantially changing cell morphology, cell-laden hydrogels were cultured in the 0.24 kPa gels for 3 days to allow VIC spreading, and then stiffenedin situvia a second, photoinitiated thiol-ene polymerization such that the gel modulus increased from 0.24 kPa to 1.2 kPa or 13 kPa. VICs encapsulated within soft gels exhibited αSMA stress fibers (∼40%), a hallmark of the myofibroblast phenotype. Interestingly, in stiffened gels, VICs became deactivated to a quiescent fibroblast phenotype, suggesting that matrix stiffness directs VIC phenotype independent of morphology, but in a manner that depends on the dimensionality of the culture platform. Collectively, these studies present a versatile method for dynamic stiffening of hydrogels and demonstrate the significant effects of matrix modulus on VIC myofibroblast properties in three-dimensional environments.
登录
查看更多内容
影响因子：
14
作者：
Benton, Julie A.;Fairbanks, Benjamin D.;Anseth, Kristi S.
通讯作者：
Anseth, Kristi S.
影响因子：
37.8
作者：
Aikawa, E;Whittaker, P;Schoen, FJ
通讯作者：
Schoen, FJ
影响因子：
41.2
作者：
Khetan S;Guvendiren M;Legant WR;Cohen DM;Chen CS;Burdick JA
通讯作者：
Burdick JA
影响因子：
14
作者：
Kural, Mehmet H.;Billiar, Kristen L.
通讯作者：
Billiar, Kristen L.
DOI：
10.1073/pnas.0903269107
发表时间：
2010-03-16
影响因子：
11.1
作者：
Kilian, Kristopher A.;Bugarija, Branimir;Mrksich, Milan
通讯作者：
Mrksich, Milan