Synthesis and characterization of in situ forming anionic hydrogel as vitreous substitutes

J Biomed Mater Res B Appl Biomater. 2017 Jul;105(5):977-988. doi: 10.1002/jbm.b.33632. Epub 2016 Feb 13.

Abstract

The natural vitreous is a biological hydrogel consisting primarily of a collagen and anionic hyaluronate. It is surgically removed in many ocular diseases and replaced with fluids, gases, or silicone oils. We have been interested in developing synthetic hydrogels as vitreous substitutes. In this study, we combined the stiffness and hydrophobicity of polymethacrylamide (PMAM) and the anionic nature of polymethacrylate (PMAA) to make copolymers that would mimic the natural vitreous. We used bis-methacryloyl cystamine (BMAC) to introduce thiol groups for reversible crosslink. The Mn of copolymers ranged from ∼100 k to ∼200 k Da (polydisperisty index of 1.47-2.63) and their composition as determined by titration, 1 H NMR and disulfide test were close to the feed ratio. The reactivities of monomers were as follows: MAM > MAA ∼ BMAC. Copolymers with higher MAA contents gelled faster, swelled more, and had higher storage modulus (1.5 to 100 Pa) comparable to that of the natural vitreous. We evaluated the biocompatibility of copolymers by electric cell-substrate impedance sensing (ECIS) using human retinal pigment epithelial cells, primary porcine retinal pigmented epithelial cells, human microvascular endothelial cells adult dermis, and a fibroblast line 3T3. The biocompatibility decreases as the content of BMAC increases. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 977-988, 2017.

Keywords: ECIS; in situ forming hydrogel; reversible crosslink; vitreous substitute.

Publication types

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

MeSH terms

  • Animals
  • Epithelial Cells / cytology
  • Epithelial Cells / metabolism*
  • Humans
  • Hydrogels* / chemical synthesis
  • Hydrogels* / chemistry
  • Hydrogels* / pharmacology
  • Materials Testing*
  • Mice
  • NIH 3T3 Cells
  • Polymethacrylic Acids* / chemical synthesis
  • Polymethacrylic Acids* / chemistry
  • Polymethacrylic Acids* / pharmacology
  • Retinal Pigment Epithelium / cytology
  • Retinal Pigment Epithelium / metabolism*
  • Swine
  • Vitreous Body*

Substances

  • Hydrogels
  • Polymethacrylic Acids