Collagen scaffolds functionalised with copper-eluting bioactive glass reduce infection and enhance osteogenesis and angiogenesis both in vitro and in vivo

Biomaterials. 2019 Mar:197:405-416. doi: 10.1016/j.biomaterials.2019.01.031. Epub 2019 Jan 23.

Abstract

The bone infection osteomyelitis (typically by Staphylococcus aureus) usually requires a multistep procedure of surgical debridement, long-term systemic high-dose antibiotics, and - for larger defects - bone grafting. This, combined with the alarming rise in antibiotic resistance, necessitates development of alternative approaches. Herein, we describe a one-step treatment for osteomyelitis that combines local, controlled release of non-antibiotic antibacterials with a regenerative collagen-based scaffold. To maximise efficacy, we utilised bioactive glass, an established osteoconductive material with immense capacity for bone repair, as a delivery platform for copper ions (proven antibacterial, angiogenic, and osteogenic properties). Multifunctional collagen-copper-doped bioactive glass scaffolds (CuBG-CS) were fabricated with favourable microarchitectural and mechanical properties (up to 1.9-fold increase in compressive modulus over CS) within the ideal range for bone tissue engineering. Scaffolds demonstrated antibacterial activity against Staphylococcus aureus (up to 66% inhibition) whilst also enhancing osteogenesis (up to 3.6-fold increase in calcium deposition) and angiogenesis in vitro. Most significantly, when assessed in a chick embryo in vivo model, CuBG-CS not only demonstrated biocompatibility, but also a significant angiogenic and osteogenic response, consistent with in vitro studies. Collectively, these results indicate that the CuBG-CS developed here show potential as a one-step osteomyelitis treatment: reducing infection, whilst enhancing bone healing.

Keywords: Angiogenesis; Antibacterial; Bioactive glass; Copper; Osteogenesis; Osteomyelitis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inducing Agents / administration & dosage*
  • Angiogenesis Inducing Agents / pharmacology
  • Animals
  • Anti-Bacterial Agents / administration & dosage*
  • Anti-Bacterial Agents / pharmacology
  • Biocompatible Materials / chemistry
  • Cell Line
  • Chick Embryo
  • Collagen / chemistry*
  • Copper / administration & dosage*
  • Copper / pharmacology
  • Drug Delivery Systems
  • Glass / chemistry
  • Mice
  • Neovascularization, Physiologic / drug effects
  • Osteogenesis / drug effects*
  • Staphylococcal Infections / drug therapy
  • Staphylococcus aureus / drug effects
  • Tissue Scaffolds / chemistry*

Substances

  • Angiogenesis Inducing Agents
  • Anti-Bacterial Agents
  • Biocompatible Materials
  • Copper
  • Collagen