In Vitro Macrophage Immunomodulation by Poly(ε-caprolactone) Based-Coated AZ31 Mg Alloy

Int J Mol Sci. 2021 Jan 18;22(2):909. doi: 10.3390/ijms22020909.

Abstract

Due to its excellent bone-like mechanical properties and non-toxicity, magnesium (Mg) and its alloys have attracted great interest as biomaterials for orthopaedic applications. However, their fast degradation rate in physiological environments leads to an acute inflammatory response, restricting their use as biodegradable metallic implants. Endowing Mg-based biomaterials with immunomodulatory properties can help trigger a desired immune response capable of supporting a favorable healing process. In this study, electrospun poly(ε-caprolactone) (PCL) fibers loaded with coumarin (CM) and/or zinc oxide nanoparticles (ZnO) were used to coat the commercial AZ31 Mg alloy as single and combined formulas, and their effects on the macrophage inflammatory response and osteoclastogenic process were investigated by indirect contact studies. Likewise, the capacity of the analyzed samples to generate reactive oxygen species (ROS) has been investigated. The data obtained by attenuated total reflection Fourier-transform infrared (FTIR-ATR) and X-ray photoelectron spectroscopy (XPS) analyses indicate that AZ31 alloy was perfectly coated with the PCL fibers loaded with CM and ZnO, which had an important influence on tuning the release of the active ingredient. Furthermore, in terms of degradation in phosphate-buffered saline (PBS) solution, the PCL-ZnO- and secondary PCL-CM-ZnO-coated samples exhibited the best corrosion behaviour. The in vitro results showed the PCL-CM-ZnO and, to a lower extent, PCL-ZnO coated sample exhibited the best behaviour in terms of inflammatory response and receptor activator of nuclear factor kappa-B ligand (RANKL)-mediated differentiation of RAW 264.7 macrophages into osteoclasts. Altogether, the results obtained suggest that the coating of Mg alloys with fibrous PCL containing CM and/or ZnO can constitute a feasible strategy for biomedical applications.

Keywords: PCL-coating; electrochemical behaviour; inflammatory response; macrophage; magnesium alloy; osteoclastogenesis.

MeSH terms

  • Alloys / pharmacology*
  • Animals
  • Biodegradable Plastics / chemistry
  • Biodegradable Plastics / pharmacology
  • Coumarins / chemistry
  • Coumarins / pharmacology
  • Gene Expression Regulation / drug effects
  • Humans
  • Immunomodulation / drug effects
  • Inflammation / drug therapy*
  • Inflammation / genetics
  • Inflammation / pathology
  • Macrophages / drug effects
  • Magnesium / chemistry
  • Magnesium / pharmacology
  • Metal Nanoparticles / chemistry
  • Mice
  • Osteogenesis / drug effects*
  • Polyesters / pharmacology*
  • RANK Ligand / genetics*
  • RAW 264.7 Cells
  • Spectroscopy, Fourier Transform Infrared
  • Zinc Oxide / pharmacology

Substances

  • Alloys
  • Biodegradable Plastics
  • Coumarins
  • Mg-Al-Zn-Mn-Si-Cu alloy
  • Polyesters
  • RANK Ligand
  • Tnfsf11 protein, mouse
  • polycaprolactone
  • coumarin
  • Magnesium
  • Zinc Oxide