Date of Award
Doctor of Philosophy
Joel D Bumgardner
Warren O Haggard
The incidence of infection and non-union in severe musculoskeletal fractures continues to plague the medical community. This work investigated calcium sulfate (CS)-chitosan composite scaffolds with dual drug delivery capabilities. The aim of this dissertation is to investigate potential strategies for a dual delivery composite scaffolds that will allow for sufficient delivery of two therapeutic agents to control infection and regrow bone. Initial work focused on a chitosan microspheres-composite for delivery of antibiotics and growth factors. The dual delivery of antibiotics from both the CS and chitosan components was an approach to treat polymicrobial infections, while the dual delivery of an antibiotic from CS and growth factor from the chitosan component was aimed at bone regeneration to treat fractures that require additional therapies to stimulate bone healing while preventing an infection. The effectiveness of the dual antibiotic loaded scaffold to eliminate infection was depended on the amount of drugs loaded and if the drugs were delivered together or separate. Vancomycin released from the dual loaded scaffold sustained almost 5 weeks of bacterial growth inhibition, whereas the amikacin release inhibited bacterial growth for only one day. The composite scaffold loaded with vancomycin and a growth factor, rhBMP-2, had extended bacterial inhibition and killing. The rhBMP-2 release was delayed 2 days and had a low-level extended elution over 6 weeks. The activity of rhBMP-2 could not be determined, and it was found that the level of rhBMP-2 released might not have been high enough to stimulate cells in vitro. To increase the rhBMP-2 elution, mechanical integrity, and make channels for vascularization ingrowth, chitosan meshes were substituted for the microspheres in the third study. While the meshes increased the vancomycin elution, no change in rhBMP-2 elution was found. The meshes did improve the ability of the scaffold to remain intact under mechanical forces. While further research into the biological activity of released rhBMP-2 and in vivo evaluation of the scaffold must be performed, our research demonstrates the successful dual delivery of therapeutic agents from a composite scaffold that could be used as an adjunctive therapy for infected musculoskeletal fractures.
dissertation or thesis originally submitted to the local University of Memphis Electronic Theses & dissertation (ETD) Repository.
Doty, Heather Alisa, "Dual Drug Delivery with Calcium Sulfate-Chitosan Based Scaffolds for Bone Regeneration and Infection Control" (2015). Electronic Theses and Dissertations. 1277.