Gadolinium-doped mesoporous calcium silicate/chitosan scaffolds enhanced bone regeneration ability

Mater Sci Eng C Mater Biol Appl. 2019 Nov:104:109999. doi: 10.1016/j.msec.2019.109999. Epub 2019 Jul 19.

Abstract

Chitosan (CTS) and mesoporous calcium silicate (MCS) have been developed for bone defect healing; however, their bone regeneration capacity still does not satisfy the patients with bone diseases. Gadolinium (Gd) is accumulated in human bones, and plays a beneficial role in regulating cell performance and bone regeneration. We firstly constructed Gd-doped MCS/CTS (Gd-MCS/CTS) scaffolds by a lyophilization technology. The interconnected arrangement of CTS films lead to forming macropores by using ice crystals as templates during the lyophilization procedure, and the Gd-MCS nanoparticles dispersed uniformly on the macropore walls. The biocompatible chemical components and hierarchical pores facilitated the attachment and spreading of rat bone marrow-derived mesenchymal stem cells (rBMSCs). Interestingly, the Gd dopants in the scaffolds effectively activated the Wnt/β-catenin signaling pathway, resulting in excellent cell proliferation and osteogenic differentiation capacities. The osteogenic-related genes such as alkaline phosphatase (ALP), runt-related transcription factor 2 (Runx2) and collagen type1 (COL-1) were remarkably up-regulated by Gd-MCS scaffolds as compared with MCS scaffolds, and their expression levels increased in a positive correlation with Gd doping amounts. Moreover, in vivo rat cranial defect tests further confirmed that Gd-MCS/CTS scaffolds significantly stimulated collagen deposition and new bone formation. The exciting finding suggested the beneficial effects of Gd3+ ions on osteogenic differentiation and new bone regeneration, and Gd-MCS/CTS scaffolds can be employed as a novel platform for bone defect healing.

Keywords: Biocompatibility; Bone scaffolds; Chitosan; Gadolinium; Osteogenic activity.

MeSH terms

  • Alkaline Phosphatase / metabolism
  • Animals
  • Biocompatible Materials / chemistry
  • Bone Regeneration / drug effects*
  • Bone and Bones / drug effects
  • Bone and Bones / metabolism
  • Calcium Compounds / chemistry*
  • Calcium Compounds / pharmacology*
  • Cell Differentiation / drug effects
  • Cell Proliferation / drug effects
  • Chitosan / chemistry*
  • Core Binding Factor Alpha 1 Subunit / metabolism
  • Gadolinium / chemistry*
  • Gadolinium / pharmacology*
  • Male
  • Mesenchymal Stem Cells / drug effects
  • Mesenchymal Stem Cells / metabolism
  • Osteogenesis / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Silicates / chemistry*
  • Silicates / pharmacology*
  • Tissue Engineering / methods
  • Tissue Scaffolds / chemistry
  • Up-Regulation / drug effects

Substances

  • Biocompatible Materials
  • Calcium Compounds
  • Core Binding Factor Alpha 1 Subunit
  • Silicates
  • Chitosan
  • Gadolinium
  • Alkaline Phosphatase
  • calcium silicate