Antibiotic-releasing microspheres prevent mesh infection in vivo

Grafmiller, Kevin; Zuckerman, Sean T.; Petro, Clayton C.; Liu, Lijia; Recum, Horst A. von; Rosen, Michael J.; Korley, Julius N.

doi:10.1016/j.jss.2016.06.099

Cited by 40 publications

(52 citation statements)

References 20 publications

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“…A bolus antibiotic injection serves to eradicate the planktonic bacteria surrounding the initial infection, while the implanted affinity polymer serves as an antibiotic depot slowly re-administer drug to eradicate the less metabolically active bacteria that are present in biofilm. Affinity polymer filled with vancomycin prior to implantation has already been shown to prevent device infection in rodents [41,42] and has also prevented Methicillin-resistant S. aureus (MRSA) hernia defect infection in pigs (manuscript submitted). The versatility of affinity polymers makes them amenable for use in both hard and soft tissue applications.…”

Section: Discussionmentioning

confidence: 99%

Affinity interactions drive post-implantation drug filling, even in the presence of bacterial biofilm

Cyphert

Zuckerman²,

Korley³

et al. 2017

Acta Biomaterialia

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Current post-operative standard of care for surgical procedures, including device implantations, dictates prophylactic antimicrobial therapy, but a percentage of patients still develop infections. Systemic antimicrobial therapy needed to treat such infections can lead to downstream tissue toxicities and generate drug-resistant bacteria. 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 polymer can be used as an implant coating or stand-alone drug delivery device, and can be translated to a variety of applications, such as implanted or indwelling medical devices, and/or surgical site infections. The filling of empty affinity-based drug delivery polymer was analyzed in an in vitro filling/refilling model mimicking post-implantation tissue conditions. Filling in the absence of bacteria was compared to filling in the presence of bacterial biofilms of varying maturity to demonstrate proof-of-concept necessary prior to in vivo experiments. Antibiotic filling into biofilm-coated affinity polymers was comparable to drug filling seen in same affinity polymers without biofilm demonstrating that affinity polymers retain ability to fill with antibiotic even in the presence of biofilm. Additionally, post-implantation filled antibiotics showed sustained bactericidal activity in a zone of inhibition assay demonstrating post-implantation capacity to deliver filled antibiotics in a timeframe necessary to eradicate bacteria in biofilms. 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.

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Section: Discussionmentioning

confidence: 99%

Affinity interactions drive post-implantation drug filling, even in the presence of bacterial biofilm

Cyphert

Zuckerman²,

Korley³

et al. 2017

Acta Biomaterialia

Self Cite

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“…Mechanical changes were found to be significant, and there is evidence that polymer coatings are vulnerable to cracking. Even though polymer cracking does not induce delamination, there is evidence based on previous work, that fragments of polymer coating (i.e., particles) remain equally good delivery vehicles as compared to coated materials.…”

Section: Discussionmentioning

confidence: 98%

“…Once the dual-loading solution was determined, drug loading of pCD was carried out as mentioned previously, and according to previously determined protocol. 43 After 72 h of loading, sutures were blotted on KimWipes and briefly rinsed with water to remove surface DMF and any free drug which is not loaded. Rinsed sutures were left to dry at 23 C overnight.…”

Section: Methodsmentioning

confidence: 99%

Use of affinity allows anti‐inflammatory and anti‐microbial dual release that matches suture wound resolution

Haley

Qian

Learn

et al. 2019

J Biomedical Materials Res

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Surgical sutures are vulnerable to bacterial infections and biofilm formation. At the suture site, pain and undesirable, excess inflammation are additionally detrimental to wound healing. The development of a polymerized cyclodextrin (pCD) coated surgical suture introduces the capability to locally deliver both anti‐inflammatory and anti‐microbial drugs throughout the phases of acute and chronic healing. Local delivery allows for the improvement of wound healing while reducing related systemic side effects and drug resistance. Through testing, it has been shown that the fabrication of our pCD coating minimally affects the suture's mechanical properties. In vitro studies show measurable and consistent drug delivery for nearly 5 weeks. The therapeutic level of this delivery is sufficient to show inhibition of bacterial growth for 4 weeks, and free‐radical scavenging (an in vitro anti‐inflammatory activity approximation) for 2 weeks. With this pCD coating technique, we maintain clinical performance standards while also introducing a long‐term dual delivery system relevant to the wound healing timeframe. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2019.

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“…Insoluble polymerized cyclodextrin microparticles were synthesized according to a previously published methodology 17 26 .…”

Section: Synthesis Of Insoluble Polymerized Cyclodextrin (β-Cd) Micromentioning

confidence: 99%

Combination antibiotic PMMA composites provide sustained broad-spectrum antimicrobial activity and allow for post-implantation refilling

Chen

et al. 2019

Preprint

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Antibiotics are commonly added to poly(methyl methacrylate) (PMMA) by surgeons to locally treat infections such as in bone cement for joint replacement surgeries, but also as implantable antimicrobial "beads". However, this strategy is of limited value in high risk patients where infections can be recurrent or chronic and otherwise hard to treat. Also when only one drug is incorporated and applied toward poly-microbial infections (multiple bacterial species), there is a high risk that bacteria can develop antibiotic resistance. To combat these limitations, we developed a combination-antibiotic PMMA composite system comprised of rifampicin-filled β cyclodextrin (β-CD) microparticles added into PMMA filled with a second drug. Different formulations were evaluated through Zone-of-Inhibition, drug activity, antibiotic release and refilling, as well as mechanical studies. Our combination-antibiotic PMMA composite system achieved up to an eight-fold increase in 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. Mechanical testing showed that our tested formulations did have a small, but significant decrease in mechanical properties when compared to unmodified controls. While further studies are needed to determine whether the tested formulations are still suitable for loadbearing applications (e.g. bone cement), our composites are certainly amenable for a variety of non-load bearing applications (e.g. antimicrobial "beads" and temporary spacer in two-stage arthroscopic revisions).

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Antibiotic-releasing microspheres prevent mesh infection in vivo

Cited by 40 publications

References 20 publications

Affinity interactions drive post-implantation drug filling, even in the presence of bacterial biofilm

Affinity interactions drive post-implantation drug filling, even in the presence of bacterial biofilm

Use of affinity allows anti‐inflammatory and anti‐microbial dual release that matches suture wound resolution

Combination antibiotic PMMA composites provide sustained broad-spectrum antimicrobial activity and allow for post-implantation refilling

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