Osteogenic citric acid linked chitosan coating of 3D-printed PLA scaffolds for preventing implant-associated infections

Int J Biol Macromol. 2024 Dec;282(Pt 3):136968. doi: 10.1016/j.ijbiomac.2024.136968. Epub 2024 Oct 28.

Abstract

>25 % of the patients who receive orthopedic implants have been reported with implant-associated osteomyelitis, which can result in inflammation, osteolysis, and aseptic loosening of implants. Current treatment methods doesn't ensure defect healing and prevention from reinfection. Thermoplastic-based 3D-printed scaffolds offer a bioresorbable, biocompatible, and mechanical strong implant system. However, the hydrophobicity and bio-inertness of these polymers prevent their use in clinics. In this study, we developed dual functionalized scaffolds with osteogenic and antibacterial properties by immobilizing citric acid-linked chitosan on oxygen plasma etched 3D-printed PLA scaffolds through an EDC-NHS coupling reaction. Acellular mineralization of these scaffolds in DMEM demonstrated the deposition of crystalline hydroxyapatite. In addition, the antibacterial properties of these surface-modified scaffolds have been determined against E. coli and S. aureus, where the citric-linked chitosan biofunctionalized 3D-printed PLA scaffolds showed significantly higher antibacterial activity in comparison to oxygen-etched PLA and PLA scaffolds due to the synergistic effect of citric acid and chitosan functionalities. MG-63 cells exhibited increased proliferation and osteogenic activity on the modified scaffolds compared to the PLA and OP-PLA. These 3D-printed scaffolds, coated with citric-linked chitosan, can be a potential solution to orthopedic complications such as critical-sized bone defects and implant-associated osteomyelitis.

Keywords: Bone; Chitosan; Citric acid; Mineralization; PLA; Tissue engineering.

MeSH terms

  • Anti-Bacterial Agents* / chemistry
  • Anti-Bacterial Agents* / pharmacology
  • Cell Proliferation / drug effects
  • Chitosan* / chemistry
  • Chitosan* / pharmacology
  • Citric Acid* / chemistry
  • Citric Acid* / pharmacology
  • Coated Materials, Biocompatible / chemistry
  • Coated Materials, Biocompatible / pharmacology
  • Escherichia coli / drug effects
  • Humans
  • Osteogenesis* / drug effects
  • Polyesters* / chemistry
  • Printing, Three-Dimensional*
  • Prosthesis-Related Infections / prevention & control
  • Staphylococcus aureus / drug effects
  • Tissue Scaffolds* / chemistry

Substances

  • Chitosan
  • Citric Acid
  • poly(lactide)
  • Polyesters
  • Anti-Bacterial Agents
  • Coated Materials, Biocompatible