Particles of vaterite, a metastable CaCO3 polymorph, exhibit high biocompatibility for human osteoblasts and endothelial cells and may serve as a biomaterial for rapid bone regeneration

J Tissue Eng Regen Med. 2018 Jul;12(7):1754-1768. doi: 10.1002/term.2703. Epub 2018 Jun 10.

Abstract

We have previously described a promising alternative to conventional synthetic bone biomaterials using vaterite, a metastable CaCO3 polymorph that increases the local Ca2+ concentration in vitro and leads to an oversaturation of phosphate, the primary bone mineral. This stimulates a natural bone-like mineralisation in a short period of time. In this study, sterile and endotoxin-free vaterite particles were synthesised in a nearly quantitative yield. The 500-1,000 nm vaterite particles did not exhibit any cytotoxic effects as measured by MTS, lactate dehydrogenase, or crystal violet assays on the human osteoblast cell line (MG-63) exposed to concentrations up to 500 μg/ml vaterite up to 72 hr. MG-63, primary human osteoblasts or human umbilical vein endothelial cells in the presence of vaterite up to 500 μg/ml for 7 days exhibited typical growth patterns. Endothelial cells exhibited a normal induction of E-selectin after exposure to LPS and MG-63 cells in osteogenic differentiation medium showed an increased expression of alkaline phosphatase compared with the respective control cells without vaterite. MG-63 cultured on a vaterite-containing degradable poly(ethylene glycol)-hydrogel exhibited strong adhesion and proliferation, similar to cells on cell culture plates. Cells did not attach to gels without vaterite. Our results demonstrate that vaterite particles are biocompatible, do not influence cell gene expression, and that vaterite in hydrogels may be able to serve for adhesion of osteoblasts and as a mineral substrate for natural bone formation by osteoblasts. These characteristics make vaterite particles a highly favourable compound for use in bone regeneration applications.

Keywords: PEG hydrogel; bone regeneration; cell compatibility; endothelial cells; gene expression; osteoblast cells; vaterite particles.

MeSH terms

  • Biocompatible Materials* / chemistry
  • Biocompatible Materials* / pharmacology
  • Bone Regeneration / drug effects*
  • Calcium Carbonate* / chemistry
  • Calcium Carbonate* / pharmacology
  • Cell Differentiation / drug effects*
  • Cell Line
  • Human Umbilical Vein Endothelial Cells / cytology
  • Human Umbilical Vein Endothelial Cells / metabolism*
  • Humans
  • Osteoblasts / cytology
  • Osteoblasts / metabolism*
  • Osteogenesis / drug effects

Substances

  • Biocompatible Materials
  • Calcium Carbonate