Calcium Alginate Gels as Stem Cell Matrix – Making Paracrine Stem Cell Activity Available for Enhanced Healing after Surgery

• Published in: PloS one Vol. 10; no. 3; p. e0118937
• Main Authors: Schmitt, Andreas, Rödel, Philipp, Anamur, Cihad, Seeliger, Claudine, Imhoff, Andreas B., Herbst, Elmar, Vogt, Stephan, van Griensven, Martijn, Winter, Gerhard, Engert, Julia
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 20.03.2015; Public Library of Science (PLoS)
• Subjects: Acids; Alginates - pharmacology; Alginic acid; Animals; Biomedical materials; Bovine serum albumin; Calcium; Calcium alginate; Calcium Chloride - pharmacology; Cattle; Cell culture; Cell Survival - drug effects; Fibroblast growth factor 2; Fibroblast growth factors; Fluorescence; Fluorescence microscopy; Gelation; Gels; Gels - pharmacology; Glucuronic Acid - pharmacology; Growth factors; Healing; Heparan sulfate; Hexuronic Acids - pharmacology; Humans; Hyaluronic acid; Hydrogel, Polyethylene Glycol Dimethacrylate - pharmacology; Hydrogels; Immobilization; Immunoassay; Injectability; Intercellular Signaling Peptides and Proteins - pharmacology; Lysozyme; Mechanical Phenomena; Mechanical properties; Mesenchymal stem cells; Mesenchymal Stromal Cells - cytology; Mesenchymal Stromal Cells - drug effects; Mesenchyme; Muramidase - metabolism; Orthopedics; Paracrine Communication - drug effects; Paracrine signalling; Permeability; Phaeophyceae; Pharmaceutical sciences; Polyethylene; Polyethylene glycol; Polyols; Product enhancement; Proteins; Regeneration; Serum albumin; Serum Albumin, Bovine - metabolism; Sodium; Stem cells; Studies; Surface stability; Surgery; Tissue engineering; Transplants & implants; Trauma; Vascular endothelial growth factor; Viscosity; Wound Healing - drug effects; Austria; Germany
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0118937

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.