The impact of functional groups of poly(ethylene glycol) macromers on the physical properties of photo-polymerized hydrogels and the local inflammatory response in the host

Acta Biomater. 2018 Feb;67:42-52. doi: 10.1016/j.actbio.2017.12.007. Epub 2017 Dec 12.

Abstract

Poly(ethylene glycol) (PEG) can be functionalized and modified with various moieties allowing for a multitude of cross-linking chemistries. Here, we investigate how vinyl sulfone, acrylate, and maleimide functional end groups affect hydrogel formation, physical properties, viability of encapsulated cells, post-polymerization modification, and inflammatory response of the host. We have shown that PEG-VS hydrogels, in the presence of a co-monomer, N-vinyl-2-pyrrolidone (NVP), form more efficiently than PEG-Ac and PEG-Mal hydrogels, resulting in superior physical properties after 6 min of ultraviolet light exposure. PEG-VS hydrogels exhibited hydrolytic stability and non-fouling characteristics, as well as the ability to be modified with biological motifs, such as RGD, after polymerization. Additionally, unmodified PEG-VS hydrogels resulted in lesser inflammatory response, cellular infiltration, and macrophage recruitment after implantation for 28 days in mice. These findings show that altering the end group chemistry of PEG macromer impacts characteristics of the photo-polymerized network. We have developed a tunable non-degradable PEG system that is conducive for cell or tissue encapsulation and evokes a minimal inflammatory response, which could be utilized for future immunoisolation applications.

Statement of significance: The objective of this study was to develop a tunable non-degradable PEG system that is conducive for encapsulation and evokes a minimal inflammatory response, which could be utilized for immunoisolation applications. This study has demonstrated that reactive functional groups of the PEG macromers impact free radical mediated network formation. Here, we show PEG-VS hydrogels meet the design criteria for an immunoisolating device as PEG-VS hydrogels form efficiently via photo-polymerization, impacting bulk properties, was stable in physiological conditions, and elicited a minimal inflammatory response. Further, NVP can be added to the precursor solution to expedite the cross-linking process without impacting cellular response upon encapsulation. These findings present an additional approach/chemistry to encapsulate cells or tissue for immunoisolation applications.

Keywords: Functional groups; Inflammatory response; Photo-polymerization; Poly(ethylene glycol); RGD modification.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Cell Survival / drug effects
  • Cross-Linking Reagents / chemistry
  • Elastic Modulus
  • Embryo, Mammalian / cytology
  • Female
  • Fibroblasts / cytology
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Hydrogels / chemistry
  • Hydrolysis
  • Implants, Experimental
  • Inflammation / pathology*
  • Light*
  • Mice
  • Oligopeptides / metabolism
  • Polyethylene Glycols / chemistry*
  • Polymerization*
  • Protective Agents / pharmacology
  • Pyrrolidinones / chemistry
  • Sulfones / chemistry

Substances

  • Cross-Linking Reagents
  • Hydrogels
  • Oligopeptides
  • Protective Agents
  • Pyrrolidinones
  • Sulfones
  • Polyethylene Glycols
  • divinyl sulfone
  • N-vinyl-2-pyrrolidinone
  • arginyl-glycyl-aspartic acid