| dc.description.abstract | Osteomyelitis or bone infections remain very difficult to treat despite advances in treatment regimens and surgical technics. The bone microenvironment and compromised vasculature in addition to infected prosthesis and implants that were put in the bone during prior surgery impedes the antibiotic partition into the bone from systemic therapy in many cases. Treatment often includes surgical debridement of the infected bone and surrounding tissue, removal of implants, systemic antibiotic therapy accompanied with antibiotic containing bone void filler, in most cases polymethylmethacylate (PMMA) based bone cement. Unfortunately, PMMA has many associated problems, including non-biodegradability, inconsistent antibiotic release, and a surface susceptible to bacterial biofilm growth, ultimately necessitating removal and causing recurrent infections. Thus, recent studies have focused on designing novel bone void filling materials to deliver antibiotics and to support bone regeneration.
There are two parts to designing a successful bone void filling device/material:(1) local release antibiotic for infection treatment and (2) development of a bone graft substitute to support bone regrowth. In this study, antibiotic releasing bone void filler (ABVF) putty formulations have been designed and tested. Different formulations were examined in this dissertation to describe the three components of the putty formulation - polymer, drug, and substrate. In the first formulation, different custom-made polymers were used to control drug release; Pro Osteon, a hydroxyapatite (HA) and calcium carbonate based bone graft substitute was used to provide support for bone growth. Finally, vancomycin was used as the antibiotic as it is clinically used to treat Staphylococcus aureus, the primary cause of osteomyelitis. In second formulation, commercially available and clinically used polymers, poly(lactic-co-glycolic acid) (PLGA), polycaprolactone (PCL) and, polyethylene glycol (PEG), were used to make the ABVF putty along with Pro Osteon and vancomycin. In the subsequent formulations, delivering combination antibiotics - vancomycin and rifampicin - to treat biofilm infections and, using bioglass (BG) as the substrate for faster bone regrowth were explored; PLGA, PCL and PEG constituted the polymer matrix.
The ABVF putty formulations were customizable in terms of three primary components: polymers, bone graft substitutes, antibiotics. Ultimately, these were successful in curing infection and providing bone growth support. | en_US |
