Free radical functionalization of surfaces to prevent adverse responses to biomedical devices

Abstract

Immobilizing a protein, that is fully compatible with the patient, on the surface of a biomedical device should make it possible to avoid adverse responses such as inflammation, rejection, or excessive fibrosis. A surface that strongly binds and does not denature the compatible protein is required. Hydrophilic surfaces do not induce denaturation of immobilized protein but exhibit a low binding affinity for protein. Here, we describe an energetic ion-assisted plasma process that can make any surface hydrophilic and at the same time enable it to covalently immobilize functional biological molecules. We show that the modification creates free radicals that migrate to the surface from a reservoir beneath. When they reach the surface, the radicals form covalent bonds with biomolecules. The kinetics and number densities of protein molecules in solution and free radicals in the reservoir control the time required to form a full protein monolayer that is covalently bound. The shelf life of the covalent binding capability is governed by the initial density of free radicals and the depth of the reservoir. We show that the high reactivity of the radicals renders the binding universal across all biological macromolecules. Because the free radical reservoir can be created on any solid material, this approach can be used in medical applications ranging from cardiovascular stents to heart-lung machines.

Plasma ion implantation enabled bio-functionalization of PEEK improves osteoblastic activity

“…Covalent tropoelastin attachment saturated at a coating concentration of 5 lg/ml and a PIII treatment time of 120 s. Tropoelastin immobilization to PIII treated surfaces is achieved through reactions with radicals generated by the PIII treatment on the surface. 37 The generation and final concentration of radicals present in a sub-surface layer are functions of ion fluence, which in turn are functions of treatment time. 36 To ensure that the surfaces were sufficiently activated with radicals and coated with a full monolayer of tropoelastin, a PIII treatment time of 800 s and a tropoelastin coating concentration of 20 lg/ml were selected for subsequent experiments.…”

“…Selected samples were washed with 5% (w/v) sodium dodecyl sulfate (SDS) in PBS at 80 C for 10 min to remove the non-covalently bound protein, 32,37,45,46 then rinsed in Milli-Q water, and dried before obtaining a post-SDS FTIR spectrum. …”

“…33,34 These unpaired electrons are present in radicals that diffuse throughout the polymer to covalently react with molecules at the surface, 35 such as atmospheric oxygen 36 or biomolecules in solution. 37 PEEK, PIII treated under identical conditions as utilized in this study, exhibits dynamic properties characterized by progressive oxidation of the surface 36 and a decreasing concentration of radicals. 35 These dynamic surface properties stabilize after 7 days to produce a stable hydrophilic surface.…”

A Survey of Surface Modification Techniques for Next-Generation Shape Memory Polymer Stent Devices

“…Bilek et al, found that treatment of a polymer surface with ions to create a free radical surface encourages protein immobilization while retaining protein structure, potentially enhancing biocompatibility [77]. Photo-oxidation, a method to introduce hydrophilic groups to polymer surfaces in a controlled manner through the manipulation of photo-oxidation time and grafting time, has also been shown to be beneficial to endothelial cell development on the material surface [32].…”

“…PIII treatment of polymers has been shown to reduce thrombus formation and platelet aggregation by increasing hydrophilicity and protein adsorption onto the surface, as displayed in Figure 5 [77]. Chemical vapor deposition (CVD) utilizes plasma or other reactive chemicals to deposit thin films onto the surface of the material, slightly altering the surface to allow for deposition of the film [64,78].…”