Much discussion has focused on the possible inflammatory and thrombogenic influences of the polymer coating on drug‐eluting stents (DES) and the potential for late stent thrombosis. Biodegradable polymers and/or microporous materials are being evaluated by others. In this study, we have used Argon based GCIB to adhere the drug to the surface of a metal. GCIB bombardment results in surface modification of the top 100Å, allowing a thin coating of drug to adhere to the surface without polymer. Titanium foils cut into 1.5cm2 pieces were initially processed with GCIB at 5x1014 Ar clusters/cm2. 50μg of rapamycin (RAP) was placed on the surface; one group received a GCIB drug surface processing while another group did not. Pieces of foil were placed in plasma at 37oC on a rotator to simulate in vivo drug elution for up to 14 days (n=3). Pre‐ and post‐ eluted foils were then placed in plates and 104 mouse endothelial cells were seeded per foil, allowed to attach for 24 hours, and counts were measured by MTS assay. RAP on foils not receiving the second modification by GCIB eluted off within 24 hours and increased cell attachment from 576±403 cells (pre‐eluted) to 8876±1170 (24h post‐eluted, p<0.01). Foils that received a second GCIB modification caused the RAP to be eluted off more slowly, requiring 72 hours before cell attachment matched no‐drug controls (p<0.05). Therefore, GCIB could replace polymers as a drug delivery method for DES.
Titanium implants are considered to be bioactive, but osseointegration is often slow. Many have increased surface area of the implant to which osteoblasts bind by etching or sandblasting, and applied additive coatings such as hydroxyapatite. We have altered the atomic‐level structure of the TiO2 surface without adding material onto the surface. GCIB utilizes high energy ionized gas clusters of inert argon atoms. Bombardment of TiO2 results in increased surface wettability and amorphization. Ti pieces were divided into 2 groups: untreated, or GCIB irradiated with 5×1014 Ar clusters/cm2. Osteoblasts were seeded at 2000 cells/cm2, allowed to attach and proliferate up to 10 days (n=3). Cell counts were measured by MTS assay. RNA was extracted over 10 days and amplified for alkaline phosphatase (ALPL). Protein was extracted at 4, 24, and 48h and probed for total and phosphorylated p42, as a marker for cell proliferation. GCIB‐treated TiO2 showed: increased proliferation by day 10 (12,213 ± 1,570 vs 6,880 ±700 cells p<0.05); ALPL upregulated by 3.4 ± 0.6 (p<0.01) fold by day 10, indicating bone formation; phosphorylation of p42 is seen at 4h and sustained at 24h on GCIB‐treated, and only 4h on non‐treated surfaces. Results suggest that osteoblasts adhere and proliferate better on GCIB‐treated TiO2. GCIB treatment of dental implants has potential to enhance bone formation and significantly decrease osseointegration time.
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