Calcium alginate gels as stem cell matrix-making paracrine stem cell activity available for enhanced healing after surgery

PLoS One. 2015 Mar 20;10(3):e0118937. doi: 10.1371/journal.pone.0118937. eCollection 2015.

Abstract

Regeneration after surgery can be improved by the administration of anabolic growth factors. However, to locally maintain these factors at the site of regeneration is problematic. The aim of this study was to develop a matrix system containing human mesenchymal stem cells (MSCs) which can be applied to the surgical site and allows the secretion of endogenous healing factors from the cells. Calcium alginate gels were prepared by a combination of internal and external gelation. The gelling behaviour, mechanical stability, surface adhesive properties and injectability of the gels were investigated. The permeability of the gels for growth factors was analysed using bovine serum albumin and lysozyme as model proteins. Human MSCs were isolated, cultivated and seeded into the alginate gels. Cell viability was determined by AlamarBlue assay and fluorescence microscopy. The release of human VEGF and bFGF from the cells was determined using an enzyme-linked immunoassay. Gels with sufficient mechanical properties were prepared which remained injectable through a syringe and solidified in a sufficient time frame after application. Surface adhesion was improved by the addition of polyethylene glycol 300,000 and hyaluronic acid. Humans MSCs remained viable for the duration of 6 weeks within the gels. Human VEGF and bFGF was found in quantifiable concentrations in cell culture supernatants of gels loaded with MSCs and incubated for a period of 6 weeks. This work shows that calcium alginate gels can function as immobilization matrices for human MSCs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alginates / pharmacology*
  • Animals
  • Calcium Chloride / pharmacology
  • Cattle
  • Cell Survival / drug effects
  • Gels / pharmacology*
  • Glucuronic Acid / pharmacology
  • Hexuronic Acids / pharmacology
  • Humans
  • Hydrogel, Polyethylene Glycol Dimethacrylate / pharmacology
  • Intercellular Signaling Peptides and Proteins / pharmacology
  • Mechanical Phenomena
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / drug effects
  • Muramidase / metabolism
  • Paracrine Communication / drug effects*
  • Serum Albumin, Bovine / metabolism
  • Viscosity
  • Wound Healing / drug effects*

Substances

  • Alginates
  • Gels
  • Hexuronic Acids
  • Intercellular Signaling Peptides and Proteins
  • Hydrogel, Polyethylene Glycol Dimethacrylate
  • Serum Albumin, Bovine
  • Glucuronic Acid
  • Muramidase
  • Calcium Chloride

Grants and funding

This work was supported by the German Research Foundation (DFG) and the Technische Universität München within the funding programme Open Access Publishing. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.