The local delivery of anti-proliferative compounds from drug eluting stents (DES) has successfully reduced rates of restenosis following stent implantation. However, somewhat higher rates of late stent thrombosis are perceived for DES compared to their bare metal counterparts. This article looks at a promising approach to address this issue.Surface modification has proven an effective method of enhancing the performance of medical devices at their biological interfaces. Materials used in the manufacture of early medical devices were selected primarily based upon their availability for industrial applications. Not surprisingly, the surface properties of first-generation devices were not optimized for use in the human body. While it is sometimes possible to improve interfacial properties by altering bulk materials used in fabrication, it is often easier and more effective to apply a thin-film coating to the surface of an existing device. Success stories range from hydrophilic coatings that increase lubricity of catheters passed through peripheral blood vessels to access the heart, to drug-eluting coatings on stents that keep coronary blood vessels patent (open). While these coatings improve device function, emerging next generation coatings improve device performance by promoting healing-in of devices with healthy tissue.
While implanted medical devices have improved the lives of countless patients, they are nonetheless foreign materials to the human body. As such, they are prone to adverse biological reactions including infection, thrombosis, inflammation, cellular hypertrophy, and fibrosis. The body’s response to implanted medical devices comprises a series of events, beginning with acute inflammatory response, followed by chronic inflammatory response, granulation tissue development, and foreign body reaction to implanted biomaterials.1 The intensity and time course of each depends upon factors such as the extent of injury, and the size, shape, topography, and chemical and physical properties of the implanted biomaterials. The outcome is often the encapsulation of the device in collagenous, avascular, fibrous tissue. Integration of the device with healthy, vascularized, natural tissue has been an elusive goal for both academics and medical device manufacturers.
Drug-eluting stents and vascular grafts represent typical medical device applications complicated by delayed or incomplete endothelialization. While drug-eluting stents (DES) reduce the incidence of coronary artery restenosis compared with bare metal stents (BMS), recent controversy has lessened the use of DES. Finn et al. report that DES impair arterial healing characterized by incomplete reendothelialization and persistence of fibrin leading to late stent thrombosis.2 Could an ECM protein coating promote the formation of a healthy endothelium on a DES rendering it resistant to late stent thrombosis?
To determine the effect of the ECM coatings upon stent healing, a double-injury rabbit iliac artery model predictive of human coronary artery healing was selected.3 Briefly, the vessels of healthy New Zealand White rabbits were first denuded of endothelium prior to stenting by balloon inflation injury without damaging the internal elastic lamina. Stents were randomly implanted in the right and left iliac arteries (one stent per iliac), then retrieved 7 and 14 days later. Retrieved stents were filleted open and examined en face using bisbenzimide (BBI) nuclear stain and scanning electron microscopy (SEM) to evaluate endothelial coverage.
SurModics’ Finale Prohealing family of ECM coatings is the result of a 15-year collaboration between SurModics and Dr. Stuart K. Williams (scientific director at the Cardiovascular Innovation Institute in Louisville, KY) and the University of Arizona. Finale coatings use proven PhotoLink technology to attach extracellular matrix (ECM) proteins to the surface of devices fabricated of materials including durable polymers, degradable polymers, and metals.
Vascular grafts perform adequately in large diameters where cellular hypertrophy and resulting lumenal loss do not significantly impede blood flow. However, grafts in humans typically endothelialize only at the ends, leaving the mid-graft susceptible to both thrombosis and infection. When implanted subcutaneously in rats, a prohealing coating improved both angiogenic response (blood vessels in the tissue adjacent to the implant) and neovascularization (blood vessels penetrating the fabric porosity) of e-PTFE fabric relative to controls (Figure 3), as well as greatly enhanced tissue integration into the fabric. This result suggests that ECM prohealing coatings may not only improve the healing of large diameter grafts, but also enable small diameter grafts.
Tissue healing of multiple non-vascular applications may be improved with ECM prohealing coatings, such as neuromodulation, implanted sensors, ophthalmic implants, and tissue reconstruction. While particular ECM coatings may perform differently in vascular and non-vascular systems, ECM proteins in general affect cells throughout the body and might therefore improve the function of most implanted devices.
1 Anderson JM, “Inflammation, Wound Healing, and the Foreign-Body Response,” in Biomaterials Science: An Introduction to Materials in Medicine, 2nd Ed. Buddy D. Ratner, Allan S. Hoffman, Frederick J. Schoen, and Jack E. Lemons, Eds. (Elsevier Academic Press, 2004), pp. 296-303.
2 Finn, Aloke V; et al. “Vascular Responses to Drug Eluting Stents. Importance of Delayed Healing,” Arteriosclerosis, Thrombosis, and Vascular Biology. 2007; 27:1500.
3 Farb, Andrew; et al. “Pathological Analysis of Local Delivery of Paclitaxel Via a Polymer-Coated Stent,” Circulation, 2001;104:473.
OnlineFor additional information on the technologies and products discussed in this article, visit SurModics at www.surmodics.com.
Dr. Joseph A. Chinn. is a technical advisor for the SurModics Regenerative Technologies business. He is responsible for providing cardiovascular technical expertise to SurModics’ customers. Dr. Chinn can be reached at (952) 947-8640 or firstname.lastname@example.org.