  Bone infection is a feared complication following surgery or trauma that
remains as an extremely difficult disease to deal with. So far, the outcome of
therapy could be improved with the design of 3D implants, which combine the
merits of osseous regeneration and local multidrug therapy so as to avoid
bacterial growth, drug resistance and the feared side effects. Herein,
hierarchical 3D multidrug scaffolds based on nanocomposite bioceramic and
polyvinyl alcohol (PVA) prepared by rapid prototyping with an external coating
of gelatin-glutaraldehyde (Gel-Glu) have been fabricated. These 3D scaffolds
contain three antimicrobial agents (rifampin, levofloxacin and vancomycin),
which have been localized in different compartments of the scaffold to obtain
different release kinetics and more effective combined therapy. Levofloxacin
was loaded into the mesopores of nanocomposite bioceramic part, vancomycin was
localized into PVA biopolymer part and rifampin was loaded in the external
coating of Gel-Glu. The obtained results show an early and fast release of
rifampin followed by sustained and prolonged release of vancomycin and
levofloxacin, respectively, which are mainly governed by the progressive in
vitro degradability rate of these scaffolds. This combined therapy is able to
destroy Gram-positive and Gram-negative bacteria biofilms as well as inhibit
the bacteria growth; in addition, these multifunctional scaffolds exhibit
excellent bioactivity as well as good biocompatibility with complete cell
colonization of preosteoblast in the entire surface, ensuring good bone
regeneration. These findings suggest that these hierarchical 3D multidrug
scaffolds are promising candidates as platforms for local bone infection
therapy.
