Biomimetic trace metals improve bone regenerative properties of calcium phosphate bioceramics

J Biomed Mater Res A. 2021 May;109(5):666-681. doi: 10.1002/jbm.a.37051. Epub 2020 Jul 14.

Abstract

The bone regenerative capacity of synthetic calcium phosphates (CaPs) can be enhanced through the enrichment with selected metal trace ions. However, defining the optimal elemental composition required for bone formation is challenging due to many possible concentrations and combinations of these elements. We hypothesized that the ideal elemental composition exists in the inorganic phase of the bone extracellular matrix (ECM). To study our hypothesis, we first obtained natural hydroxyapatite through the calcination of bovine bone, which was then investigated its reactivity with acidic phosphates to produce CaP cements. Bioceramic scaffolds fabricated using these cements were assessed for their composition, properties, and in vivo regenerative performance and compared with controls. We found that natural hydroxyapatite could react with phosphoric acid to produce CaP cements with biomimetic trace metals. These cements present significantly superior in vivo bone regenerative performance compared with cements prepared using synthetic apatite. In summary, this study opens new avenues for further advancements in the field of CaP bone biomaterials by introducing a simple approach to develop biomimetic CaPs. This work also sheds light on the role of the inorganic phase of bone and its composition in defining the regenerative properties of natural bone xenografts.

Keywords: bioceramics; bone extracellular matrix; bone regeneration; trace metals.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomimetics*
  • Bone Cements / chemistry
  • Bone Regeneration / drug effects*
  • Calcium Phosphates / chemistry
  • Calcium Phosphates / pharmacology*
  • Cattle
  • Ceramics / pharmacology*
  • Citric Acid / pharmacology
  • Compressive Strength
  • Crystallography, X-Ray
  • Durapatite / chemistry
  • Durapatite / isolation & purification
  • Female
  • Materials Testing
  • Metals / analysis
  • Metals / pharmacology*
  • Metals / therapeutic use
  • Phosphoric Acids / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Spectroscopy, Fourier Transform Infrared
  • Tibia / diagnostic imaging
  • Tibia / drug effects
  • Tibia / injuries
  • Trace Elements / analysis
  • Trace Elements / pharmacology*
  • Trace Elements / therapeutic use
  • X-Ray Microtomography

Substances

  • Bone Cements
  • Calcium Phosphates
  • Metals
  • Phosphoric Acids
  • Trace Elements
  • Citric Acid
  • Durapatite
  • calcium phosphate
  • phosphoric acid
  • calcium phosphate, dibasic, dihydrate