Gregory T. Zugates

Drug Eluting Medical Implant

Drug-eluting medical implants are actually active implants that induce healing effects, in addition to their regular task of support. This effect is achieved by controlled release of active pharmaceutical ingredients (API) into the surrounding tissue. In this chapter we focus on three types of drug-eluting devices: drug-eluting vascular stents, drug-eluting wound dressings and protein-eluting scaffolds for tissue regeneration, thus describing both internal and external implants. Each of these drug-eluting devices also presents an approach for solving the drug release issue. Most drug-eluting vascular stents are loaded with water-insoluble antiproliferative agents, and their diffusion from the device to the surrounding tissue is relatively slow. In contrast, most drug-eluting wound dressings are loaded with highly water-soluble antibacterial agents and the issue of fast release must therefore be addressed. Growth factor release from scaffolds for tissue regeneration offers a new approach of incorporating high-molecular-weight bioactive agents which are very sensitive to process conditions and preserve their activity during the preparation stage. The drug-eluting medical implants are described here in terms of matrix formats and polymers, incorporated drugs and their release profiles from the implants, and implant functioning. Basic elements, such as new composite core/shell fibers and structured films, can be used to build new antibiotic-eluting devices. As presented in this chapter, the effect of the processing parameters on the microstructure and the resulting drug release profiles, mechanical and physical properties, and other relevant properties, must be elucidated in order to achieve the desired properties. Newly developed implants and novel modifications of previously developed approaches have enhanced the tools available for creating clinically important biomedical applications.

Self-expanding polyurethane polymer improves survival in a model of noncompressible massive abdominal hemorrhage.

BACKGROUND Intracavitary noncompressible hemorrhage remains a significant cause of preventable death on the battlefield. Two dynamically mixed and percutaneously injected liquids were engineered to create an in situ self-expanding polymer foam to facilitate hemostasis in massive bleeding. We hypothesized that intraperitoneal injection of the polymer could achieve conformal contact with sites of injury and improve survival in swine with lethal hepatoportal injury. METHODS High grade hepatoportal injury was created in a closed abdominal cavity, resulting in massive noncoagulopathic, noncompressible hemorrhage. Animals received either standard battlefield fluid resuscitation (control, n = 12) or fluid resuscitation plus intraperitoneal injection of hemostatic foam (polymer, n = 15) and were monitored for 3 hours. Blood loss was quantified, and all hepatoportal injuries were inspected for consistency. RESULTS Before intervention, all animals initially experienced severe, profound hypotension and near-arrest (mean arterial pressure at 10 minutes, 21 [5.3] mm Hg). Overall survival at 3 hours was 73% in the polymer group and 8% in the control group (p = 0.001). Median survival time was more than 150 minutes in the polymer group versus 23 minutes (19–41.5 minutes) in the control group (p < 0.001), and normalized blood loss in the polymer group was 0.47 (0.30) g/kg per minute versus 3.0 (1.3) g/kg per minute in the controls (p = < 0.001). All hepatoportal injuries were anatomically similar, and the polymer had conformal contact with injured tissues. CONCLUSION Intraperitoneal polymer injection during massive noncompressible hemorrhage reduces blood loss and improves survival in a lethal, closed-cavity, hepatoportal injury model. Chronic safety and additional efficacy studies in other models are needed.

Chronic safety assessment of hemostatic self-expanding foam: 90-day survival study and intramuscular biocompatibility.

BACKGROUND Noncompressible hemorrhage is a significant cause of preventable death in trauma, with no effective presurgical treatments. We previously described the efficacy and 28-day safety of a self-expanding hemostatic foam in swine models. We hypothesized that the 28-day results would be confirmed at a second site and that results would be consistent over 90 days. Finally, we hypothesized that the foam material would be biocompatible following intramuscular implantation. METHODS Foam treatment was administered in swine following a closed-cavity splenic injury. The material was explanted after 3 hours, and the animals were monitored to 28 days (n = 6) or 90 days (n = 4). Results were compared with a control group with injury alone (n = 6 at 28 days, n = 3 at 90 days). In a separate study, foam samples were implanted in rabbit paravertebral muscle and assessed at 28 days and 90 days relative to a Food and Drug Administration–approved polyurethane mesh (n = 3 per group). RESULTS All animals survived the acute phase of the study, and the foam animals required enterorrhaphy. One animal developed postoperative ileus and was euthanized; all other animals survived to the 28-day or 90-day end point without clinically significant complications. Histologic evaluation demonstrated that remnant particles were associated with a fibrotic capsule and mild inflammation. The foam was considered biocompatible in 28-day and 90-day intramuscular implant studies. CONCLUSION Foam treatment was not associated with significant evidence of end-organ dysfunction or toxicity at 28 days or 90 days. Remnant foam particles were well tolerated. These results support the long-term safety of this intervention for severely bleeding patients.