(C-112) Rationale Design of Anti-Biofouling Superelastic Stent

Introduction::

Sub-track: Natural and Bioinspired Biomaterials

Medical devices implanted into the body must withstand the natural foreign body response, often risking bacterial infection, blood clotting, or device malfunction. To address these challenges, we proposed the use of a drug-eluting stent that incorporates a slippery liquid-infused porous surface (SLIPS) onto a TiNi base substrate. This alloy material is unique as it has superelastic properties enabling the material to deform during surgery, while promptly returning to its original shape after deployment. Such manipulability makes this an ideal candidate for medical devices that may be inserted via minimally invasive techniques in a whole range of applications such as brain aneurysms, heart stents, and more. 

The coating consists of a multilayer nanoparticle system which creates a highly porous matrix.  Subsequently, the pores are infused with a biocompatible lubricant, allowing it to repel and prevent the adhesion of various pathogens, microorganisms, and cellular debris. In our work, we demonstrate the conformal adherence of the SLIPS coating on TiNi substrates, showcase extreme omniphobic repellency, and mechanical stability under various loading conditions. The material system proposed herein has a range of applications to reduce infection risk post-surgery, increase patency of the device, and improve flow within the conduit. Moreover, the TiNi-SLIPS coated devices have capabilities of being drug-loadable allowing for a plethora of treatments to be administered such as antibiotics, anti-inflammatory drugs, or even cancer treatment small molecules.

Materials and Methods::

Materials

Poly(diallyldimethylammonium) chloride (PDADMAC), Ludox HS-40 colloidal silica, and silicone oil 350 cP were purchased from Sigma-Aldrich, St. Louis, MO. (1H,1H,2H,2H-tetrahydrotridecafluorooctyl)-trichlorosilane was procured from Oakwood Chemical, Estill, South Carolina. All scanning electron microscope (SEM) images were taken using a Zeiss Gemini 360 (Oberkochen, Germany). Structured free-standing films were fabricated using photolithography, wet chemical etching of the sacrificial layer of copper, and magnetron sputtering, further details described in Bechtold et al. (Shape Mem. Superelasticity, 2015).

Layer-by-Layer Coating

TiNi surface was negatively charged by oxygen plasma for 5 minutes. It was then submerged into 0.1 wt% solution of PDADMAC for 10 minutes, deionized water for 1 minute, 0.1 wt% Ludox nanoparticles for 10 minutes, and deionized water for 1 minute. This cycle was repeated to ultimately achieve 20 multilayers. PDADMAC was removed by calcination at 500 °C leaving a porous surface composed of nanoparticles. Silicone oil (50 μl cm–2) was added to the substrate uniformly.

Contact Angle Measurements

Goniometer was used to measure the static contact angle, sliding contact angle, and contact angle hysteresis of 20 μL of deionized water and dimethyl sulfoxide (DMSO). All measurements were averaged over 3 droplets. The sliding angle was censored after a 25° tilt. 

Mechanical Testing 

Instron tensile machine was used to obtain stress-strain curves of TiNi material with and without layer-by-layer coating. SEM images were taken before and after strain to confirm the stability of the coating. 

Results, Conclusions, and Discussions::

Confirmation of Coating Process on TiNi Substrate

The first step of the experiment was to confirm that the multilayer deposition could be stable on the TiNi substrate. SEM images of the substrates after each step of the procedure (deposition of nanoparticle/polymer multilayers, calcination, functionalization, 1-hour bake) are shown in Figure 1. The results were expected as the nanoparticles and polymer are arranged in an amorphous, porous structure, indicating that SLIPS can be performed on TiNi. The average particle size was 13.620 nm +/- 2.431 nm (n=15) with 18.46% free space. 

Multilayer Conformal SLIPS on TiNi Substrate

To assess the surface's ability to repel pathogens, microorganisms, and cellular debris, we conducted measurements of static contact angle, contact angle hysteresis, and sliding angle using deionized water and DMSO as test liquids. The non-SLIPS TiNi samples showed significant pinning as they lacked the lubrication necessary for superhydrophobic properties. This resulted in high contact angle hysteresis and the inability to remove the droplet after a tilt angle of 25°. Deionized water had a 112.6 +/- 10.0 contact angle and was greater than 36.6° +/- 12.7° for contact angle hysteresis (CAH). In contrast, the TiNi substrate post-lubrication with silicone oil (350 cP) had 94.9° +/- 7.3° contact angle, 4.2° +/- 5.3° CAH, and 4.4° +/- 5.2° sliding angle, confirming the high degree of repellency.

Conclusion & Discussion 

We have developed a way to introduce the SLIPS coating to a biocompatible superelastic alloy. Stent-related complications, specifically restenosis and thrombosis, are extremely common as there is a foreign body response to any unknown material. This stent combines the advantages of both technologies, SLIPS and superelasticity, and could be utilized in a broad range of applications including coronary and carotid stents.

Acknowledgements (Optional): :

References (Optional): : Bechtold, C., Lima de Miranda, R. & Quandt, E. Capability of Sputtered Micro-patterned NiTi Thick Films. Shap. Mem. Superelasticity 1, 286–293 (2015). https://doi.org/10.1007/s40830-015-0029-9