No abstract

The long-term prevention of biofilm formation on the surface of indwelling medical devices remains a challenge. Silver has been reutilized in recent years for combating biofilm formation due to its indisputable bactericidal potency; however, the toxicity, low stability, and short-term activity of the current silver coatings have limited their use. Here, we report the development of silver-based film-forming antibacterial engineered (SAFE) assemblies for the generation of durable lubricous antibiofilm surface long-term activity without silver toxicity that was applicable to diverse materials via a highly scalable dip/spray/solution-skinning process. The SAFE coating was obtained through a large-scale screening, resulting in effective incorporation of silver nanoparticles (∼10 nm) into a stable nonsticky coating with high surface hierarchy and coverage, which guaranteed sustained silver release. The lead coating showed zero bacterial adhesion over a 1 month experiment in the presence of a high load of diverse bacteria, including difficult-to-kill and stone-forming strains. The SAFE coating showed high biocompatibility and excellent antibiofilm activity in vivo.

A major medical device-associated complication is the biofilm-related infection post-implantation. One promising approach to prevent this is to coat already commercialized medical devices with effective antibiofilm materials. However, developing a robust high-performance antibiofilm coating on devices with a nonflat geometry remains unmet. Here, we report the development of a facile scalable nanoparticle-based antibiofilm silver composite coating with long-term activity applicable to virtually any objects including difficult-to-coat commercially available medical devices utilizing a catecholic organic–aqueous mixture. Using a screening approach, we have identified a combination of the organic–aqueous buffer mixture which alters polycatecholamine synthesis, nanoparticle formation, and stabilization, resulting in controlled deposition of in situ formed composite silver nanoparticles in the presence of an ultra-high-molecular-weight hydrophilic polymer on diverse objects irrespective of its geometry and chemistry. Methanol-mediated synthesis of polymer–silver composite nanoparticles resulted in a biocompatible lubricious coating with high mechanical durability, long-term silver release (∼90 days), complete inhibition of bacterial adhesion, and excellent killing activity against a diverse range of bacteria over the long term. Coated catheters retained their excellent activity even after exposure to harsh mechanical challenges (rubbing, twisting, and stretching) and storage conditions (>3 months stirring in water). We confirmed its excellent bacteria-killing efficacy (>99.999%) against difficult-to-kill bacteria (Proteus mirabilis) and high biocompatibility using percutaneous catheter infection mice and subcutaneous implant rat models, respectively, in vivo. The developed coating approach opens a new avenue to transform clinically used medical devices (e.g., urinary catheters) to highly infection-resistant devices to prevent and treat implant/device-associated infections.

Current assessment and management of ascending thoracic aortic aneurysm (ATAA) rely heavily on the diameter of the ATAA and blood pressure rather than biomechanical and hemodynamic parameters such as arterial wall deformation or wall shear stress. The objective of the current study was to develop an accurate computational method for modeling the mechanical responses of the ATAA to provide additional information in patient evaluations. Fully coupled fluid structure interaction simulations were conducted using data from cases with ATAA with measured geometrical parameters in order to evaluate and analyze the change in biomechanical responses under normotensive and hypertensive conditions. Anisotropic hyperelastic material property estimates were applied to the ATAA data which represented three different geometrical configurations of ATAAs. The resulting analysis showed significant variations in maximum wall shear stress despite minimal differences in flow velocity between two blood pressure conditions. Additionally, the three different ATAA conditions identified different aortic expansions that were not uniform under pulsatile pressure. The elevated wall stress with hypertension was also geometry-dependent. The developed models suggest that ATTA cases have unique characteristic in biomechanical and hemodynamic evaluations that can be useful in risk management.

BACKGROUND: Noncompressible truncal hemorrhage (NCTH) remains a leading cause of preventable death on the battlefield. Definitively managing severe NCTH requires surgery within the first hour after injury, which is difficult when evacuating casualties from remote and austere environments. During delays to surgery, hemostatic interventions that are performed prehospital can prevent coagulopathy and hemorrhagic shock and increase the likelihood that casualties survive to receive definitive care. We previously reported that a self-propelling thrombin-containing powder (SPTP) can be delivered percutaneously into the abdomen as a minimally invasive intervention and can self-disperse through pooled blood to deliver the hemostatic agents thrombin and tranexamic acid locally to noncompressible intracavitary wounds. We hypothesized that, in swine with massive NCTH, dilutional coagulopathy, and hypothermia, delivering SPTP could extend survival times. METHODS:Ten swine (n = 5 per group) underwent NCTH from a Grade V liver injury following a midline laparotomy. The laparotomy was closed with sutures afterwards, creating a hemoperitoneum, and animals were managed with crystalloid fluid resuscitation, or crystalloid resuscitation and SPTP. Self-propelling thrombin-containing powder was delivered into the closed abdomen using a CO 2 -powered spray device and a catheter placed into the hemoperitoneum, entering through the upper right quadrant using the Seldinger technique. Survival to 1 and 3 hours was recorded. In an additional animal, hemorrhage was created laparoscopically, and SPTP was imaged in situ within the abdomen to visually track dispersion of the particles. RESULTS:Self-propelling thrombin-containing powder dispersed as far as 35 ± 5.0 cm within the abdomen. It increased survival to 1 and 3 hours (Kaplan-Meier p = 0.007 for both). The median survival time was 61 minutes with SPTP and 31 minutes without ( p = 0.016). CONCLUSION: Self-propelling thrombin-containing powder effectively disperses medications throughout a hemoperitoneum and increases survival in a model of NCTH. It is a promising strategy for nonsurgical management of NCTH, warranting further testing of its safety and efficacy.