Bioengineering stents with proactive biocompatibility — ASN Events
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Bioengineering stents with proactive biocompatibility (#349)

Thamarasee Jeewandara 1 2 , Anna Waterhouse 3 , Steven Wise 1 3 , Yongbai Yin 4 , Marcela Bilek 4 , Anthony Weiss 3 , Martin Ng 1 2
  1. Heart Research Institute, Sydney, Non-U, Australia
  2. Faculty of Medicine, University of Sydney, Sydney, NSW, Australia
  3. School of Molecular and Microbial Biosciences, University of Sydney, Sydney, NSW, Australia
  4. Physics School, Applied and Plasma Physics Group, University of Sydney, Sydney, NSW, Australia

Introduction:
Commercially available stents are only sub-optimally biocompatible leading to intrinsic thrombogenicity, restenosis due to smooth muscle cell (SMC) hyperproliferation and reduced endothelialization1 . We aim to modify a 316 L stainless steel (SS) surface with a plasma activated coating (PAC), to covalently bind proteins such as tropoelastin (TE) in their active state and improve biofunctionalization, which can then be adapted to a 316L SS stent platform.

Methods:
i) Surface integrity: measured compressive stress, refractive index, contact angle, attachment of TE and percentage [N],[O] atomic composition of N2/Ar PAC compared to other PAC compositions (H2/Ar, O2/Ar). ii) Endothelialization: attachment and proliferation of endothelial cells on PAC+TE vs 316LSS assessed with crystal violet staining. iii) Thrombogenicity assays: In vitro modified chandler loop model rotated with heparinised whole blood (0.5U/mL and 0.1 U/mL for flat sheets and stents respectively) at 370C, clot formation assessed at 3 time points of 30, 60 and 90 mins for both flat sheets and stents.

Results:
i) Compressive stress (<0.25 GPa), refractive index (<1.75), wettability/contact angle (<600) and higher TE attachment after SDS washing for N2/Ar PAC compared to other coating compositions (P<0.05) ii) Endothelial cell proliferation markedly increased in PAC+TE compared to 316LSS (P<0.05). ) iii) After 30 mins there was clot formation on 316LSS, these features weren’t observed with PAC/PAC+TE flat sheets at any time point up to 60 mins2 . With stents, at 60 mins, the thrombus formation was dramatically low in PAC stents compared to BMS.

Discussion:
Lower compressive stress, lower refractive index account for higher elasticity and biointegration of material, contact angle of <600-800 indicates mild hydrophilicity for optimal cell/blood compatibility. Higher TE attachment after SDS washing on N2/Ar PAC indicates covalent attachment of TE which promotes endothelialization3 . Low thrombogenicity observed; decreases intrinsic and late stent thrombogenicity post-implantation and is a characteristic specifically important for cardiovascular devices. 

Conclusion:
Most favourable plasma coating is N2/Ar PAC and TE the best candidate for covalent attachment to the PAC flat sheet surface or stent to promote endothelialization and inhibit thrombogenicity. In vivo translational studies comparing the biocompatibility of BMS with PAC stents will be done in a porcine coronary stent model following the in vitro optimization studies of PAC  stents.  

  1. Garg S and Serruys P. Coronary Stents: Looking forward, Journal of American College of Cardiology vol. 56, S44-78. 2006
  2. Waterhouse A, Yin Y, Wise SG, Bax DV, McKenzie DR, Bilek MM, et al. The immobilization of recombinant human tropoelastin on metals using a plasma-activated coating to improve the biocompatibility of coronary stents. Biomaterials.31:8332-40. 2010.
  3. Waterhouse A, Bax DV, Wise SG, Yin YB, Dunn LL, Yeo GC, et al. Stability of a Therapeutic Layer of Immobilized Recombinant Human Tropoelastin on a Plasma-Activated Coated Surface. Pharm Res-Dordr.28:1415-21. 2011.