title: The effects of varying poly(ethylene glycol) hydrogel crosslinking density and the crosslinking mechanism on protein accumulation in three-dimensional hydrogels.
abstract: Matrix stiffness has been shown to play an important role in modulating various cell fate processes such as differentiation and cell cycle. Given that the stiffness can be easily tuned by varying the crosslinking density, poly(ethylene glycol) (PEG) hydrogels have been widely used as an artificial cell niche. However, little is known about how changes in the hydrogel crosslinking density may affect the accumulation of exogenous growth factors within 3-D hydrogel scaffolds formed by different crosslinking mechanisms. To address such shortcomings, we measured protein diffusivity and accumulation within PEG hydrogels with varying PEG molecular weight, concentration and crosslinking mechanism. We found that protein accumulation increased substantially above a critical mesh size, which was distinct from the protein diffusivity trend, highlighting the importance of using protein accumulation as a parameter to better predict the cell fates in addition to protein diffusivity, a parameter commonly reported by researchers studying protein diffusion in hydrogels. Furthermore, we found that chain-growth-polymerized gels allowed more protein accumulation than step-growth-polymerized gels, which may be the result of network heterogeneity. The strategy used here can help quantify the effects of varying the hydrogel crosslinking density and crosslinking mechanism on protein diffusion in different types of hydrogel. Such tools could be broadly useful for interpreting cellular responses in hydrogels of varying stiffness for various tissue engineering applications.
authors.affiliation: Department of Materials Science and Engineering, Stanford University, Stanford, CA, USA.
authors.forename: Soah
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Orthopedic Surgery, Stanford University, Stanford, CA, USA.
authors.forename: Xinming
authors.initials: X
authors.lastname: Tong
authors.affiliation: Department of Orthopedic Surgery, Stanford University, Stanford, CA, USA; Department of Bioengineering, Stanford University, Stanford, CA, USA. Electronic address: fanyang@stanford.edu.
authors.forename: Fan
authors.initials: F
authors.lastname: Yang
mesh_terms: D020100:Hydrogels / Q000737:chemistry*; D008422:Materials Testing; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000737:chemistry; D016062:Porosity; D012710:Serum Albumin, Bovine / Q000737:chemistry*; D023822:Tissue Engineering / Q000379:methods
chemical_list: D020100:Hydrogels; D012710:Serum Albumin, Bovine; D011092:Polyethylene Glycols
keywords: Crosslinking density; Crosslinking mechanism; Poly(ethylene glycol); Protein diffusion; Three-dimensional hydrogels