Hydrogel loaded with thiolated chitosan modified taxifolin liposome promotes osteoblast proliferation and regulates Wnt signaling pathway to repair rat skull defects

Carbohydr Polym. 2024 Jul 15:336:122115. doi: 10.1016/j.carbpol.2024.122115. Epub 2024 Apr 2.

Abstract

To alleviate skull defects and enhance the biological activity of taxifolin, this study utilized the thin-film dispersion method to prepare paclitaxel liposomes (TL). Thiolated chitosan (CSSH)-modified TL (CTL) was synthesized through charge interactions. Injectable hydrogels (BLG) were then prepared as hydrogel scaffolds loaded with TAX (TG), TL (TLG), and CTL (CTLG) using a Schiff base reaction involving oxidized dextran and carboxymethyl chitosan. The study investigated the bone reparative properties of CTLG through molecular docking, western blot techniques, and transcriptome analysis. The particle sizes of CTL were measured at 248.90 ± 14.03 nm, respectively, with zeta potentials of +36.68 ± 5.43 mV, respectively. CTLG showed excellent antioxidant capacity in vitro. It also has a good inhibitory effect on Escherichia coli and Staphylococcus aureus, with inhibition rates of 93.88 ± 1.59 % and 88.56 ± 2.83 % respectively. The results of 5-ethynyl-2 '-deoxyuridine staining, alkaline phosphatase staining and alizarin red staining showed that CTLG also had the potential to promote the proliferation and differentiation of mouse embryonic osteoblasts (MC3T3-E1). The study revealed that CTLG enhances the expression of osteogenic proteins by regulating the Wnt signaling pathway, shedding light on the potential application of TAX and bone regeneration mechanisms.

Keywords: Bone defects; Hydrogel scaffolds; Thiolated chitosan modified taxifolin liposomes.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology
  • Bone Regeneration / drug effects
  • Cell Differentiation / drug effects
  • Cell Proliferation* / drug effects
  • Chitosan* / analogs & derivatives
  • Chitosan* / chemistry
  • Chitosan* / pharmacology
  • Escherichia coli / drug effects
  • Hydrogels* / chemistry
  • Hydrogels* / pharmacology
  • Liposomes* / chemistry
  • Male
  • Mice
  • Molecular Docking Simulation
  • Osteoblasts* / drug effects
  • Osteogenesis / drug effects
  • Quercetin* / analogs & derivatives*
  • Quercetin* / chemistry
  • Quercetin* / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Skull* / drug effects
  • Skull* / metabolism
  • Skull* / pathology
  • Staphylococcus aureus / drug effects
  • Sulfhydryl Compounds / chemistry
  • Sulfhydryl Compounds / pharmacology
  • Wnt Signaling Pathway* / drug effects

Substances

  • Chitosan
  • Quercetin
  • Liposomes
  • Hydrogels
  • taxifolin
  • Sulfhydryl Compounds
  • Anti-Bacterial Agents