Physicochemical and Biological Characterisation of Diclofenac Oligomeric Poly(3-hydroxyoctanoate) Hybrids as β-TCP Ceramics Modifiers for Bone Tissue Regeneration

Int J Mol Sci. 2020 Dec 11;21(24):9452. doi: 10.3390/ijms21249452.

Abstract

Nowadays, regenerative medicine faces a major challenge in providing new, functional materials that will meet the characteristics desired to replenish and grow new tissue. Therefore, this study presents new ceramic-polymer composites in which the matrix consists of tricalcium phosphates covered with blends containing a chemically bounded diclofenac with the biocompatible polymer-poly(3-hydroxyoctanoate), P(3HO). Modification of P(3HO) oligomers was confirmed by NMR, IR and XPS. Moreover, obtained oligomers and their blends were subjected to an in-depth characterisation using GPC, TGA, DSC and AFM. Furthermore, we demonstrate that the hydrophobicity and surface free energy values of blends decreased with the amount of diclofenac modified oligomers. Subsequently, the designed composites were used as a substrate for growth of the pre-osteoblast cell line (MC3T3-E1). An in vitro biocompatibility study showed that the composite with the lowest concentration of the proposed drug is within the range assumed to be non-toxic (viability above 70%). Cell proliferation was visualised using the SEM method, whereas the observation of cell penetration into the scaffold was carried out by confocal microscopy. Thus, it can be an ideal new functional bone tissue substitute, allowing not only the regeneration and restoration of the defect but also inhibiting the development of chronic inflammation.

Keywords: bone regeneration; diclofenac; polyhydroxyalkanoates; polyhydroxyoctanoate oligomers; tricalcium phosphate composites.

MeSH terms

  • Animals
  • Bone Regeneration / drug effects
  • Calcium Phosphates / chemistry*
  • Cell Line
  • Ceramics / chemistry*
  • Ceramics / pharmacology
  • Diclofenac / chemistry*
  • Mice
  • Microscopy, Electrochemical, Scanning
  • Polyhydroxyalkanoates / chemistry*
  • Regenerative Medicine / methods
  • Tissue Engineering / methods

Substances

  • Calcium Phosphates
  • Polyhydroxyalkanoates
  • beta-tricalcium phosphate
  • Diclofenac
  • tricalcium phosphate