Morphogen and proinflammatory cytokine release kinetics from PRGF-Endoret fibrin scaffolds: evaluation of the effect of leukocyte inclusion

J Biomed Mater Res A. 2015 Mar;103(3):1011-20. doi: 10.1002/jbm.a.35244. Epub 2014 Jun 12.

Abstract

The potential influence of leukocyte incorporation in the kinetic release of growth factors from platelet-rich plasma (PRP) may explain the conflicting efficiency of leukocyte platelet-rich plasma (L-PRP) scaffolds in tissue regeneration. To assess this hypothesis, leukocyte-free (PRGF-Endoret) and L-PRP fibrin scaffolds were prepared, and both morphogen and proinflammatory cytokine release kinetics were analyzed. Clots were incubated with culture medium to monitor protein release over 8 days. Furthermore, the different fibrin scaffolds were morphologically characterized. Results show that leukocyte-free fibrin matrices were homogenous while leukocyte-containing ones were heterogeneous, loose and cellular. Leukocyte incorporation produced a significant increase in the contents of proinflammatory cytokines interleukin (IL)-1β and IL-16 but not in the platelet-derived growth factors release (<1.5-fold). Surprisingly, the availability of vascular endothelial growth factor suffered an important decrease after 3 days of incubation in the case of L-PRP matrices. While the release of proinflammatory cytokines was almost absent or very low from PRGF-Endoret, the inclusion of leukocytes induced a major increase in these cytokines, which was characterized by the presence of a latent period. The PRGF-Endoret matrices were stable during the 8 days of incubation. The inclusion of leukocytes alters the growth factors release profile and also increased the dose of proinflammatory cytokines.

Keywords: fibrin scaffold; growth factors; inflammation; leukocytes; platelet-rich plasma.

MeSH terms

  • Cell Adhesion
  • Cytokines / metabolism*
  • Epidermal Growth Factor / metabolism
  • Fibrin / chemistry
  • Hepatocyte Growth Factor / metabolism
  • Humans
  • Hydrogels / chemistry
  • Inflammation
  • Insulin / metabolism
  • Insulin-Like Growth Factor I / metabolism
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Interleukin-16 / metabolism
  • Interleukin-1beta / metabolism
  • Leukocytes / cytology*
  • Optics and Photonics
  • Platelet-Derived Growth Factor / metabolism
  • Platelet-Rich Plasma / metabolism*
  • Tissue Engineering / methods*
  • Transforming Growth Factor beta1 / metabolism
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Cytokines
  • Hydrogels
  • Insulin
  • Intercellular Signaling Peptides and Proteins
  • Interleukin-16
  • Interleukin-1beta
  • Platelet-Derived Growth Factor
  • Transforming Growth Factor beta1
  • Vascular Endothelial Growth Factor A
  • platelet-derived growth factor AB
  • Epidermal Growth Factor
  • Hepatocyte Growth Factor
  • Insulin-Like Growth Factor I
  • Fibrin