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Erika Cyphert - Dissertation Final.pdf (6.18 MB)

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Towards the creation of polymer composites which can be refilled with antibiotics after implantation for infection treatment

Cyphert, Erika Leah
http://rave.ohiolink.edu/etdc/view?acc_num=case1604071308469614

Abstract Details

2020, Doctor of Philosophy, Case Western Reserve University, Biomedical Engineering.
Periprosthetic joint infection (PJI) is one of the two leading causes of failure in arthroplasties and can develop inside of the bone as well as surrounding soft tissue. PJIs can be challenging to treat as initial diagnosis can be delayed and treatment typically involves administration of systemic antibiotics followed by removal of infected device. Traditionally, antibiotics have been directly mixed into poly(methyl methacrylate) (PMMA) bone cement to locally treat infections. However, this strategy often results in insufficient elution of drug for treatment of chronic infections and a limited range of antibiotics are compatible due to heat generated during polymerization. To overcome these shortcomings with antibiotic-PMMA, this work focused on development of PMMA composite material containing differing amounts of polymerized cyclodextrin (CD) microparticles. It was hypothesized that addition of CD microparticles to PMMA would enable post-implantation antibiotic refilling to occur and broaden the range of antibiotics compatible with PMMA to more effectively treat chronic PJIs without the need to remove the implant or expose patients to systemic antibiotics. This work first explores the emerging polymer technologies used to treat PJIs and then investigates a range of properties of PMMA containing CD microparticles and either a single or combination of antibiotics to treat broad-spectrum infections. Specifically, the porosity, compressive strength, antibiotic filling/refilling, antibiotic release, and antimicrobial properties were evaluated. Impact on functionality of CD and PMMA-CD composites in the presence of bacterial biofilm was explored. Furthermore, ex vivo models were developed to simulate how antibiotic refilling would reasonably occur in either soft or hard tissue. PMMA-CD composites were able to demonstrate refilling capacity with several antibiotics, resulting in lasting antimicrobial activity (> 60 days) to treat chronic, broad-spectrum PJIs. Composites were able to retain their mechanical properties upon addition of CD microparticles and strength was improved through use of vacuum-mixing, suggesting potential for load-bearing applications. Composites maintained their refilling properties even in presence of bacterial biofilms, demonstrating that they may not necessarily need to be removed if a biofilm forms. PMMA-CD composites have potential to serve as versatile delivery platform that is refillable and patient customizable to more effectively treat chronic PJIs.
Horst von Recum (Advisor)
Steven Eppell (Committee Chair)
Agata Exner (Committee Member)
Eben Alsberg (Committee Member)
Jonathan Pokorski (Committee Member)
287 p.
Biomedical Engineering
Infection; Antibiotics; Cyclodextrin; Orthopedics; Polymer; polymethylmethacrylate; PMMA; bone cement

Recommended Citations

Citations

  • Cyphert, E. L. (2020). Towards the creation of polymer composites which can be refilled with antibiotics after implantation for infection treatment [Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1604071308469614

    APA Style (7th edition)

  • Cyphert, Erika. Towards the creation of polymer composites which can be refilled with antibiotics after implantation for infection treatment. 2020. Case Western Reserve University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1604071308469614.

    MLA Style (8th edition)

  • Cyphert, Erika. "Towards the creation of polymer composites which can be refilled with antibiotics after implantation for infection treatment." Doctoral dissertation, Case Western Reserve University, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=case1604071308469614

    Chicago Manual of Style (17th edition)

case1604071308469614
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This open access ETD is published by Case Western Reserve University School of Graduate Studies and OhioLINK.