Collagen silver-doped hydroxyapatite scaffolds reinforced with 3D printed frameworks for infection prevention and enhanced repair of load-bearing bone defects.

Abstract

Osteomyelitis, a severe bone infection, is an extremely challenging complication in the repair of traumatic bone defects. Furthermore, the use of long-term high-dose antibiotics in standard treatment increases the risks of antibiotic resistance. Herein, an antibiotic-free, collagen silver-doped hydroxyapatite (coll-AgHA) scaffold reinforced with a 3D printed polycaprolactone (PCL) framework was developed with enhanced mechanical properties to be used in the repair of load-bearing defects with antimicrobial properties as a preventative measure against osteomyelitis. The AgHA particles were fabricated in varying Ag doses and loaded within freeze-dried collagen scaffolds at two concentrations. The optimised Ag dose (1.5 mol% Ag) and AgHA concentration (200 wt%) within the collagen scaffold demonstrated<i>in vitro</i>osteogenic and antibacterial properties against<i>S. aureus (S. aureus),</i>the main causative pathogen of osteomyelitis. The addition of the PCL framework to the coll-AgHA scaffolds significantly enhanced the compressive modulus from 4 to 12 MPa while maintaining high porosity as well as both pro-osteogenic and antibacterial properties. The reinforced coll-AgHA scaffolds were implanted<i>in vivo</i>and demonstrated enhanced bone repair, significantly greater vessel formation, and calcified tissue in a load-bearing critical sized defect in rats. Taken together, these results confirm the capacity of this novel biomaterial scaffold as a preventative measure against infection in bone repair for use in load-bearing defects, without the use of antibiotics.