Clickable, Photodegradable Hydrogels to Dynamically Modulate Valvular Interstitial Cell Phenotype. Issue 5 (24th January 2014)

• Record Type: Journal Article
• Authors: Magin, Chelsea M.; Alge, Daniel L.; Gould, Sarah T.; Anseth, Kristi S.
• Is Part Of: Advanced healthcare materials. Volume 3:Issue 5(2014:May)
• Page Start: 649
• Page End: 657
• Publication Date: 2014-01-24
• Subjects: hydrogels -- microtopographies -- photoresponsive material properties -- valvular interstitial cells -- myofibroblasts; Biomedical materials -- Periodicals; 610.28
• DOI: 10.1002/adhm.201300288
• Languages: English
• ISSNs: 2192-2640

Abstract

Abstract : Biophysical cues are widely recognized to influence cell phenotype. While this evidence was established using static substrates, there is growing interest in creating stimulus‐responsive biomaterials that better recapitulate the dynamic extracellular matrix. Here, a clickable, photodegradable hydrogel substrate that allows the user to precisely control substrate elasticity and topography in situ is presented. The hydrogels are synthesized by reacting an 8‐arm poly(ethylene glycol) alkyne with an azide‐functionalized photodegradable crosslinker. The utility of this platform by exploiting its photoresponsive properties to modulate the phenotype of porcine aortic valvular interstitial cells (VICs) is demonstrated. First, VIC phenotype is monitored, in response to initial substratum modulus and static topographic cues. Higher modulus ( E ≈ 15 kPa) substrates induce higher levels of activation (≈70% myofibroblasts) versus soft ( E ≈ 3 kPa) substrates (≈20% myofibroblasts). Microtopographies that induce VIC alignment and elongation on low modulus substrates also stimulate activation. Finally, VIC phenotype is monitored in response to sequential in situ manipulations. The results illustrate that VIC activation on stiff surfaces (≈70% myofibroblasts) can be partially reversed by reducing surface modulus (≈30% myofibroblats) and subsequently re‐activatedby anisotropic topographies (≈60% myofibroblasts). Such dynamic substrates afford unique opportunities to decipher the complex role of matrix cues on the plasticity of VIC activation. Abstract : Photolabile hydrogels provide a platform for cell culture where multiple material properties can be regulated in situ both spatially and temporally. The system can be remotely triggered by the user to modulate cell phenotype through the sequential presentation of biophysical signals such as reduction of substrate modulus and presentation of microtopographies.