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 in vitro osteogenic and antibacterial properties against Staphylococcus aureus (S. aureus), the main causative pathogen of osteomyelitis. The addition of the PCL framework to the coll-AgHA scaffolds significantly enhanced the compressive modulus from 4 kPa to 12 MPa while maintaining high porosity as well as both pro-osteogenic and antibacterial properties. The reinforced coll-AgHA scaffolds were implanted in vivo 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. .