Background Infection remains a dreaded complication after implantation of surgical prosthetics, particularly after hernia repair with synthetic mesh. We previously demonstrated the ability of a newly developed polymer to provide controlled release of an antibiotic in a linear fashion over 45 days. We subsequently showed that coating mesh with the drug-releasing polymer prevented a Staphylococcus aureus (SA) infection in vivo. In order to broaden the applicability of this technology, the polymer was synthesized as isolated “microspheres” and loaded with vancomycin (VM) before conducting a non-inferiority analysis. Materials and Methods Seventy-three mice underwent creation of a dorsal subcutaneous pocket that was inoculated with 104 CFU of green fluorescent protein (GFP)-labeled SA (105 CFU/ml). Multifilament polyester mesh (7*7mm) was placed into the pocket and the skin was closed. Mesh was either placed alone (n=16), coated with VM-loaded polymer (n=20), placed next to VM-loaded microspheres (n=20) or unloaded microspheres (n=10), or flushed with VM solution (n=7). Quantitative tissue/mesh cultures were performed at 2 and 4-weeks. Mice with open wounds and explanted mesh were excluded. Results Twenty-two of twenty-three (96%) tissue-mesh samples from mesh alone or empty miscrospheres were positive for GFP-labeled SA at two and four-weeks. Six of seven (86%) samples from the VM flush group were positive for GFP SA at 4 weeks. Thirty-eight of thirty-eight (100%) VM-loaded pCD-coated mesh or VM-loaded microspheres were negative for GFP SA at two and four weeks. Conclusion Slow affinity based drug-releasing polymers in the form of microspheres are able to adequately clear a bacterial burden of SA and prevent mesh infection.

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.

Intracortical microelectrodes are valuable tools used to study and treat neurological diseases. Due in large part to the oxidative stress and inflammatory response occurring after electrode implantation, the signal quality of these electrodes decreases over time. To alleviate this response, resveratrol, a natural antioxidant which elicits neuroprotective effects through reduction of oxidative stress, was utilized. This work compares traditional systemic delivery of resveratrol to the novel cyclodextrin polymer (pCD) local delivery approach presented herein, both in vitro and in vivo. The pCD displayed an extended resveratrol release for 100 days, as well as 60 days of free radical scavenging activity in vitro. In vivo results indicated that our pCD delivery system successfully delivered resveratrol to the brain with a sustained release for the entire short-duration study (up to 7 days). Interestingly, significantly greater concentrations of resveratrol metabolites were found at the intracortical probe implantation site compared to the systemic administration of resveratrol. Together, our pilot results provide support for the possibility of improving the delivery of resveratrol in an attempt to stabilize long-term neural interfacing applications.

Introduction Mesenchymal stem cells (MSCs) have been associated with reduced arrhythmias; however, the mechanism of this action is unknown. In addition, limited retention and survival of MSCs can significantly reduce efficacy. We hypothesized that MSCs can improve impulse conduction and that alginate hydrogel will enhance retention of MSCs in a model of healed myocardial infarction (MI). Methods and results Four weeks after temporary occlusion of the left anterior descending artery (LAD), pigs (n=13) underwent a sternotomy to access the infarct and then were divided into two studies. In study 1, designed to investigate impulse conduction, animals were administered, by border zone injection, 9–15 million MSCs (n=7) or phosphate-buffered saline (PBS) (control MI, n=5). Electrogram width measured in the border zone 2 weeks after injections was significantly decreased with MSCs (−30±8 ms, p<0.008) but not in shams (4±10 ms, p=NS). Optical mapping from border zone tissue demonstrated that conduction velocity was higher in regions with MSCs (0.49±0.03 m/s) compared to regions without MSCs (0.39±0.03 m/s, p<0.03). In study 2, designed to investigate MSC retention, animals were administered an equal number of MSCs suspended in either alginate (2 or 1 % w/v) or PBS (n=6/group) by border zone injection. Greater MSC retention and survival were observed with 2 % alginate compared to PBS or 1 % alginate. Confocal immunofluorescence demonstrated that MSCs survive and are associated with expression of connexin-43 (Cx43) for either PBS (control), 1 %, or 2 % alginate. Conclusions For the first time, we are able to directly associate MSCs with improved impulse conduction and increased retention and survival using an alginate scaffold in a clinically relevant model of healed MI.

Background Given concern for hernia mesh infection, surgeons often use biologic mesh which may provide reduced risk of infection but at the cost of decreased repair durability. We evaluated mesh coating to provide sustained release of antibiotics to prevent prosthetic mesh infection and also allow a durable repair. Materials and methods Cyclodextrin-based polymer was crosslinked onto multifilament polyester mesh and loaded with vancomycin (1.75 mg/cm2). Pigs received modified meshes (n =6) or normal, untreated meshes (n =4), which were implanted into acute 10 × 5 cm ventral hernia, then directly inoculated with 106 colony-forming unit (CFU) of methicillin-resistant Staphylococcus aureus (MRSA). These were compared to animals receiving normal, uninfected mesh. All mesh was secured in an underlay bridge manner, and after 30 d, the abdominal wall was removed for quantitative bacterial culture and biomechanical analysis. Results All animals survived 30 d. All six animals with coated mesh cleared MRSA infection. The four control animals did not clear MRSA (P =0.005). Quantitative bacterial load was higher in standard mesh versus drug-delivery mesh group (2.34×104 versus 80.9 CFU/gm). These data were log10-transformed and analyzed by Welch’s t-test (P = 0.001). Minimum number of CFUs detectable by assay (300) was used instead of zero. Biomechanical analysis of controls (1.82 N/mm infected; 1.71 N/mm uninfected) showed no difference to the modified meshes (1.31 N/mm) in tissue integration (P = 0.15). Conclusions We successfully prevented synthetic mesh infection in a pig model using a cyclodextrin-based polymer to locally deliver vancomycin to the hernia repair site and clearing antibiotic-resistant bacteria. Polymer coating did not impact the strength of the hernia repair.