Erika L. Cyphert, PhD
Peer-Reviewed Publications
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13. PMMA Bone Cement Composite Functions as an Adjuvant Chemotherapeutic Platform for Localized and Multi-Window Release During Bone Reconstruction
EL Cyphert, N Kanagasegar, N Zhang, GD Learn, HA von Recum
Macromolecular Bioscience, 2022, 2100415
In this work, a refillable chemotherapeutic (doxorubicin) delivery platform comprised of PMMA bone cement and insoluble cyclodextrin polymeric microparticles is developed and explored towards application as a temporary adjuvant chemotherapeutic spacer. Findings suggest that PMMA composites can have potential as chemotherapeutic delivery platforms to assist in bone reconstruction.
12. Recent Advances in the Evaluation of Antimicrobial Materials for Resolution of Orthopaedic Implant-Associated Infections In vivo
EL Cyphert, N Zhang, GD Learn, CJ Hernandez, HA von Recum
ACS Infectious Diseases, 2021, 7(12): 3125-3160
This review highlights the advantages and limitations of antimicrobial materials used in conjunction with orthopedic implants for the prevention and treatment of orthopaedic implant-associated infections and discusses how these materials are evaluated in preclinical in vivo models. This analysis serves as a resource for biomaterial researchers in the selection of an appropriate orthopaedic implant-associated infection preclinical model to evaluate novel antimicrobial materials.
11. Poly(methyl methacrylate) bone cement composite can be refilled with antibiotics after implantation in femur or soft tissue
EL Cyphert, N Zhang, DW Marques, GD Learn, F Zhang, HA von Recum
Journal of Functional Biomaterials, 2021, 12(1):8.
To simulate how antibiotic refilling of PMMA-cyclodextrin composite bone cement embedded in femoral tissue could reasonably occur, this work developed a refilling model. Intraosseous infusion was used to provide direct access to the bone marrow to administer antibiotics and allow for refilling of embedded PMMA-cyclodextrin. Implementation of the bone and muscle tissue refilling models developed in this work could provide insight into novel treatment options to improve outcomes for patients with chronic or prolonged peri-prosthetic joint infections.
10. Antibiotic refilling, antimicrobial activity, and mechanical strength of PMMA bone cement composites critically depend on the processing technique
EL Cyphert, GD Learn, DW Marques, C-y Lu, HA von Recum
ACS Biomaterials Science & Engineering, 2020, 6(7): 4024-4035.
The primary objective of this work was to perform an in-depth structure-function analysis regarding how processing of PMMA impacted material and structural properties (i.e., porosity) and downstream functional properties (i.e., drug refilling and strength). Knowledge of structure-function relationships can assist and provide valuable information in design and optimization of PMMA-cyclodextrin bone cement for load-bearing or non-load-bearing applications.
9. Repurposing biodegradable tissue engineering scaffolds for localized chemotherapeutic delivery
EL Cyphert, M Bil, HA von Recum, W Swieszkowski
Journal of Biomedical Materials Research Part A, 2020, 108(5): 1144-1158.
Two fabrication techniques (salt-leaching and solvent-quenching) were used to prepare different variations of poly(DL-lactide-glycolide) and poly(caprolactone)-co-poly(lactide) porous sponges. Upon fabrication, an in-depth structure-function analysis was carried out where the functions of loading capacity and release profile of cisplatin, as a model drug, were evaluated in terms of swelling, porosity, and degradation properties of the sponges. Knowledge of these relationships can be used to assist in the design of other porous delivery systems.
8. Combination antibiotic delivery in PMMA provides sustained broad-spectrum antimicrobial activity and allows for postimplantation refilling
EL Cyphert, C-y Lu, DW Marques, GD Learn, HA von Recum
Biomacromolecules, 2019, 21(2): 854-866.
We developed a combination antibiotic PMMA composite system composed of rifampicin-filled cyclodextrin microparticles added into PMMA bone cement filled with a second drug. Our combination antibiotic PMMA composite system achieved up to an 8-fold increase in the duration of antimicrobial activity in comparison to clinically used antibiotic-filled PMMA. Inclusion of CD microparticles also allowed for refilling of additional antibiotics after simulated implantation, resulting in additional windows of therapeutic efficacy.
7. An additive to PMMA bone cement enables post-implantation drug refilling, broadens range of compatible antibiotics, and prolongs antimicrobial activity
EL Cyphert, GD Learn, SK Hurley, C-y Lu, HA von Recum
Advanced Healthcare Materials, 2018, 7(21): 1800812
*Selected as cover art
To overcome limitations of antibiotic-laden bone cement, insoluble cyclodextrin microparticles are incorporated into PMMA to provide more sustained delivery of a broader range of drugs, without impacting mechanics. Findings suggest that addition of CD microparticles to cement promotes post-implantation antibiotic refilling and enables incorporation of previously incompatible antibiotics while preserving favorable mechanical properties.
6. Current options and emerging biomaterials for periprosthetic joint infection
AE Levack*, EL Cyphert *, MP Bostrom, CJ Hernandez, HA von Recum, AV Carli
Current Rheumatology Reports, 2018, 20(6): 1-9.
*Equal contributions
Infection in the setting of total joint arthroplasty, referred to as periprosthetic joint infection (PJI), is a devastating complication requiring prolonged and costly treatment. The unique environment around an artificial joint and ability of surrounding tissues to sequester bacteria collectively make prevention, diagnosis, and treatment of this condition challenging. In light of the unique pathogenesis of PJI, this review explores the limitations of contemporary treatments and discusses novel treatment options.
Current Options and Emerging Biomaterials for Periprosthetic Joint Infection | SpringerLink
5. Surface Sulfonamide Modification of Poly(N-isopropylacrylamide)-based Block Copolymer Micelles to Alter pH and Temperature Responsive Properties for Controlled Intracellular Uptake
EL Cyphert, HA von Recum, M Yamato, M Nakayama
Journal of Biomedical Materials Research Part A, 2018, 106(6): 1552-1560.
Two different surface sulfonamide-functionalized poly(N-isopropylacrylamide)-based polymeric micelles were designed as pH-/temperature-responsive vehicles. Both sulfadimethoxine- and sulfamethazine-surface functionalized micelles were characterized to determine physicochemical properties, hydrodynamic diameters, zeta potentials, temperature-dependent size changes, and lower critical solution temperatures (LCST) in both pH 7.4 and 6.8 solutions. Polymeric micelle variations have the capacity to be implemented as an intracellular drug or gene delivery system in response to mildly acidic conditions.
4. Affinity interactions drive post-implantation drug filling, even in the presence of bacterial biofilm
EL Cyphert, ST Zuckerman, JN Korkey, HA von Recum
Acta Biomaterialia, 2017, 57: 95-102
To overcome issues associated with systemic drug administration, a polymer incorporating specific drug affinity has been developed with the potential to be filled or refilled with antimicrobials, post-implantation even in the presence of bacterial biofilm. This work shows affinity polymers can fill high levels of antibiotics post-implantation independent of biofilm presence potentially enabling device rescue, rather than removal, in case of infection.
3. Erythromycin modification that improves its acidic stability while optimizing it for local drug delivery
EL Cyphert, JD Wallat, JK Pokorski, HA von Recum
Antibiotics, 2017, 6(2):11
We set out to develop a conjugate of erythromycin with improved pH stability, bioavailability, and preferential release from a drug delivery system directly at the low pH of an infection site. To develop this new drug conjugate, adamantane-1-carbohydrazide was covalently attached to erythromycin via a pH-degradable hydrazone bond. This work demonstrates the synthesis of a pH-cleavable, erythromycin conjugate that retains the inherent antimicrobial activity of erythromycin, has an increased hydrophobicility, and improved stability in acidic conditions; thereby enhancing erythromycin's bioavailability while simultaneously reducing its toxicity.
2. Chemotherapeutic delivery using pH-responsive, affinity-based release
EL Cyphert, AS Fu, HA von Recum
Experimental Biology & Medicine, 2017, 242(7): 692-699.
*Featured article
Our laboratory has explored the use of molecular interactions to control the rate of drug release beyond that capable of diffusion alone. To this system, we added an additional affinity group (adamantane) to doxorubicin through a pH-sensitive hydrazone bond. The result was a modified doxorubicin which had an even higher affinity to our drug delivery polymer, and virtually no release in normal conditions, but showed accelerated release of drug in tumor-like low pH.
1. Emerging technologies for long-term antimicrobial device coatings: advantages and limitations
EL Cyphert, HA von Recum
Experimental Biology & Medicine, 2017 242(8): 788-798.
This work provides an overview, with advantages and limitations of the most recently developed antibacterial coating technologies, enabling other researchers in the field to more easily determine which technology is most advantageous for them to further develop and pursue.
