Ex vivo pregnant-like tissue model to assess injectable hydrogel for preterm birth prevention

J Biomed Mater Res B Appl Biomater. 2020 Feb;108(2):468-474. doi: 10.1002/jbm.b.34403. Epub 2019 May 9.

Abstract

Cervical insufficiency (CI) is an important cause of preterm birth, which leads to severe newborn complications. Standard treatment for CI is cerclage, which has variable success rates, resulting in a clinical need for alternative treatments. Our objective was to develop an ex vivo model of softened cervical tissue to study an injectable silk-based hydrogel as a novel alternative treatment for CI. Cervical tissue from nonpregnant women was enzymatically treated and characterized to determine tissue hydration, collagen organization, and mechanical properties via unconfined compression. Enzymatic treatment led to an 86 ± 7.9% decrease in modulus, which correlated to a decrease in collagen organization as observed by differences in collagen birefringence. The softened tissue was injected with a crosslinked silk-hyaluronic acid composite hydrogel. After injection, the mechanical properties and volume increase of the hydrogel-treated tissue were measured resulting in a 54 ± 16% volume increase with minimal effect on tissue mechanical properties. In addition, cervical fibroblasts on silk-hyaluronic acid hydrogels remained viable and exhibited increased proliferation and metabolic activity over 5 days. Overall, this study developed an ex vivo pregnant-like human tissue model to assess cervical augmentation and showed the potential of silk-based hydrogels as an alternative treatment for cervical insufficiency.

Keywords: cervical insufficiency; cervix; hydrogel; preterm birth; silk.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Biocompatible Materials / chemistry*
  • Biocompatible Materials / metabolism
  • Cell Proliferation
  • Cervix Uteri
  • Collagen / chemistry
  • Cross-Linking Reagents / chemistry
  • Female
  • Fibroblasts / cytology
  • Humans
  • Hyaluronic Acid / chemistry
  • Hydrogels / chemistry*
  • Hydrogels / metabolism
  • Infant, Newborn
  • Injections
  • Materials Testing
  • Pregnancy
  • Premature Birth / prevention & control*
  • Silk / chemistry*
  • Silk / metabolism
  • Surface Properties
  • Tissue Engineering
  • Tissue Scaffolds / chemistry*

Substances

  • Biocompatible Materials
  • Cross-Linking Reagents
  • Hydrogels
  • Silk
  • Hyaluronic Acid
  • Collagen