Biocompatible Nanostructured Surfaces

Enhanced Cellular Responses to Metal Implants

At a Glance

Cardiovascular implants are composed of materials that cause blood to clot. Activation of the blood clotting cascade can lead to thrombosis and embolism. The placement of cardiovascular implants also damages endothelial cells (ECs) in the blood vessel, and causes smooth muscle cells (SMCs) to proliferate. This can lead to blocking of blood vessels (stenosis or restenosis). To promote healthy EC-surface interactions, this invention modifies titanium surfaces of cardiovascular implants with nano-structured titania, followed by coating with biologically derived polymers. While this coating promotes EC proliferation and migration, it does not promote SMC proliferation. This technology can be used to reduce the risk of thrombosis (by endothelializing the surface) and reduce the risk of stenosis by preventing undesirable SMC proliferation.

Background

Cardiovascular diseases (CVD) are one of the highest causes of mortality in the world and the leading cause of mortality in the United States. The main CVD-related cause of death is coronary artery disease, which is mostly caused by atherosclerosis. Vascular stents are commonly used to treat severe cases of coronary artery disease. These stents introduce a foreign surface, which can cause thrombosis and embolism. Anticoagulant therapy used to mitigate this risk is systemic and can cause other bleeding complications. Another common complication of stents is restenosis. To combat this, drug-eluting stents (DES) were developed to prevent restenosis. Although DES elute a mitotic inhibitor to prevent in-stent restenosis, they are also responsible for inhibiting the endothelialization of the stent, thus increasing the risk of late stent thrombosis. This technology combines nanotextured surfaces with glycosaminoglycan chemistries to improve endothelization and to reduce the risk thrombosis at the stent surface, potentially reducing the need for systemic anticoagulant therapy, while also reducing the risk of restenosis.

Overview

The endothelialization of nanostructured titania surfaces modified with tannin/glycosaminoglycan-based polyelectrolyte multilayers (PEMs) was investigated using in vitro cell culture of ECs and SMCs. Assays show increased cell viability when compared to other surfaces. Further, the number of cells adhered to the surfaces was dramatically increased.

Benefits

  • Enhanced endothelial cell adhesion
  • Cellular proliferation and migration on medical devices without smooth muscle cell proliferation
  • Improved hemocompatibility

Applications

  • Medical device coatings

Publications

Sabino, R.M., Kipper, M.J., Martins, A.F. et al. Improved in vitro endothelialization on nanostructured titania with tannin/glycosaminoglycan-based polyelectrolyte multilayers. In vitro models 1, 249–259 (2022). https://doi.org/10.1007/s44164-022-00024-x

Last Updated: February 2023
picture of nanostructured surface
Opportunity

Available for Licensing
TRL: 4

IP Status

US Provisional Patent

Inventors

Matt Kipper
Alessandro Martins
Ketul Popat
Roberta Maia Sabino

Reference Number
2022-058
Licensing Manager

Steve Foster
Steve.Foster@colostate.edu
970-491-7100