NOVEL FABRICATION OF A CALCIUM POLYPHOSPHATE DELIVERY MATRIX FOR TREATMENT OF OSTEOMYELITIS AND BONE REGENERATION

Abstract

Osteomyelitis is an inflammation of bone resulting from pyogenic organism activity. It affects patients of any age, impacts any bone and can lead to persistent morbidity. Local delivery systems have taken on a greater clinical focus for osteomyelitis therapy owing to their ability to overcome many disadvantages of systemic delivery. More appealing still is a device capable of eradicating infection and promoting bone regeneration. The overall aim of this research was to develop a clinically relevant, calcium polyphosphate (CPP) glass-based local delivery system for treatment of osteomyelitis and restoration of bone lost to the disease. Three specific approaches to manipulate CPP-based matrix functionality were evaluated - precipitation, strontium doping, and cold isostatic pressing.

CPP, with chain length as much as ~6X that of melt-derived CPP, was achieved following a sodium polyphosphate and calcium chloride precipitation reaction. However, this increased chain length reduced vancomycin loading efficiency of the disks and, largely owing to the presence of residual sodium in the precipitate, did not reduce early stage antibiotic release. Strontium doping of melt-derived CPP was found to increase the density and chain length of the glass. Subsequent in vitro analysis of these strontium doped CPP disks revealed greater structural stability compared to their undoped counterparts and a capacity to release greater fractions of vancomycin. Overall, observed changes in matrix hydration and vancomycin release in these first two approaches were largely attributed to differences in glass structure as a result of the presence of additional ions and their field strengths.

Finally, the capacity to predictably and reproducibly fabricate strontium-doped CPP beads using a cold isostatic pressing approach was demonstrated. In an in vitro analysis vancomycin-doped beads exhibited greater long-term structural stability compared to their blank counterparts. The vancomycin release from the beads was more controlled with detectable levels of vancomycin reported at least one week longer than for the disks. Lastly, the capacity for the strontium-doped beads to enhance osteoblast differentiation during a 12d in vitro study was demonstrated. Together these three approaches have provided evidence towards the enhanced clinical feasibility of a therapeutically loaded CPP bead-based local delivery system for osteomyelitis treatment.