Pro-Healing Nanomatrix-Coated Stent Analysis in an in Vitro Vascular Double-Layer System and in a Rabbit Model

Xixi Zhang, Jun Chen, Brigitta C. Brott, Peter G. Anderson, Patrick T.J. Hwang, Jennifer Sherwood, Gillian Huskin, Young Sup Yoon, Renu Virmani, Ho Wook Jun

Research output: Contribution to journalArticlepeer-review


Cardiovascular stent technologies have significantly improved over time. However, their optimal performance remains limited by restenosis, thrombosis, inflammation, and delayed re-endothelialization. Current stent designs primarily target inhibition of neointimal proliferation but do not promote functional arterial healing (pro-healing) in order to restore normal vascular reactivity. The endothelial lining that does develop with current stents appears to have loose intracellular junctions. We have developed a pro-healing nanomatrix coating for stents that enhances healing while limiting neointimal proliferation. This builds on our prior work evaluating the effects of the pro-healing nanomatrix coating on cultures of vascular endothelial cells (ECs), smooth muscle cells (SMCs), monocytes, and platelets. However, when a stent is deployed in an artery, multiple vascular cell types interact, and their interactions affect stent performance. Thus, in our current study, an in vitro vascular double-layer (VDL) system was used to observe stent effects on communication between different vascular cell types. Additionally, we assessed the pro-healing ability and vascular cell interactions after stent deployment in the VDL system and in a rabbit model, evaluating the nanomatrix-coated stent compared to a commercial bare metal stent (BMS) and a drug eluting stent (DES). In vitro results indicated that, in a layered vascular structure, the pro-healing nanomatrix-coated stent could (1) improve endothelialization and endothelial functions, (2) regulate SMC phenotype to reduce SMC proliferation and migration, (3) suppress inflammation through a multifactorial manner, and (4) reduce foam cell formation, extracellular matrix remodeling, and calcification. Consistent with this, in vivo results demonstrated that, compared with commercial BMS and DES, this pro-healing nanomatrix-coated stent enhanced re-endothelialization with negligible restenosis, inflammation, or thrombosis. Thus, these findings indicate the unique pro-healing features of this nanomatrix stent coating with superior efficacy over commercial BMS and DES.

Original languageEnglish
Pages (from-to)51728-51743
Number of pages16
JournalACS Applied Materials and Interfaces
Issue number46
Publication statusPublished - 2022 Nov 23

Bibliographical note

Funding Information:
This work was supported by National Institutes of Health (NIH) Grants R01HL163802 (PI: H.-W.J.), R44DK109789-05 (PI: P.H.), R43NS110114 (PI: P.H.), R43HL160311 (PI: J.S.), and R01HL150887 (PI: Y.Y.) as well as Alabama Research and Development Enhancement (ARDEF) grant ARDEF22 09 (PI: H.-W.J.).

Publisher Copyright:
© 2022 American Chemical Society. All rights reserved.

All Science Journal Classification (ASJC) codes

  • Materials Science(all)


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