3D additive manufactured composite scaffolds with antibiotic-loaded lamellar fillers for bone infection prevention and tissue regeneration

M. Camara-Torres, S. Duarte, R. Sinha, A. Egizabal, N. Alvarez, M. Bastianini, M. Sisani, P. Scopece, M. Scatto, A. Bonetto, A. Marcomini, A. Sanchez, A. Patelli, C. Mota, L. Moroni*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

18 Citations (Web of Science)

Abstract

Bone infections following open bone fracture or implant surgery remain a challenge in the orthopedics field. In order to avoid high doses of systemic drug administration, optimized local antibiotic release from scaffolds is required. 3D additive manufactured (AM) scaffolds made with biodegradable polymers are ideal to support bone healing in non-union scenarios and can be given antimicrobial properties by the incorporation of antibiotics. In this study, ciprofloxacin and gentamicin intercalated in the interlamellar spaces of magnesium aluminum layered double hydroxides (MgAl) and alpha-zirconium phosphates (ZrP), respectively, are dispersed within a thermoplastic polymer by melt compounding and subsequently processed via high temperature melt extrusion AM (similar to 190 degrees C) into 3D scaffolds. The inorganic fillers enable a sustained antibiotics release through the polymer matrix, controlled by antibiotics counterions exchange or pH conditions. Importantly, both antibiotics retain their functionality after the manufacturing process at high temperatures, as verified by their activity against both Gram + and Gram - bacterial strains. Moreover, scaffolds loaded with filler-antibiotic do not impair human mesenchymal stromal cells osteogenic differentiation, allowing matrix mineralization and the expression of relevant osteogenic markers. Overall, these results suggest the possibility of fabricating dual functionality 3D scaffolds via high temperature melt extrusion for bone regeneration and infection prevention.
Original languageEnglish
Pages (from-to)1073-1082
Number of pages10
JournalBioactive Materials
Volume6
Issue number4
DOIs
Publication statusPublished - 1 Apr 2021

Keywords

  • antibiotic delivery
  • antimicrobial activity
  • block-copolymers
  • bone infection
  • bone regeneration
  • ciprofloxacin
  • drug-delivery
  • human mesenchymal stromal cells
  • in-vitro release
  • intercalation
  • lamellar inorganic fillers
  • layered double hydroxide
  • melt extrusion additive manufacturing
  • osteoblast proliferation
  • sustained-release
  • zirconium-phosphate
  • BLOCK-COPOLYMERS
  • Lamellar inorganic fillers
  • Bone regeneration
  • DRUG-DELIVERY
  • ZIRCONIUM-PHOSPHATE
  • Antibiotic delivery
  • LAYERED DOUBLE HYDROXIDE
  • Bone infection
  • SUSTAINED-RELEASE
  • CIPROFLOXACIN
  • Melt extrusion additive manufacturing
  • IN-VITRO RELEASE
  • OSTEOBLAST PROLIFERATION
  • INTERCALATION
  • Human mesenchymal stromal cells
  • ANTIMICROBIAL ACTIVITY

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