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.
Highlights
Recent research has focused on improvement of the healing capacity of various tissues after surgery
The aim of our present study was to establish a delivery system that makes the paracrine activity of autologous mesenchymal stem cells usable to enhance regeneration after surgery
We observed a timedelayed release of calcium ions, resulting in homogenous alginate gels
Summary
Recent research has focused on improvement of the healing capacity of various tissues after surgery. Calcium Alginate Gels as Stem Cell Matrix factors (e.g. VEGF) resulted in improvement of regenerate quality and strength in different animal models [1,2,3,4,5]. Due to the low stability of the growth factors either multiple injections of recombinant proteins or stable gene transfer was necessary to achieve these results. Due to safety reasons gene transfer is presently not applicable in patients. The necessity of repetitive local injections would cause enormous costs and considerable burden for the patient with an increased infection risk. None of these treatments has yet reached patient therapy
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