Amphiphilic Macromolecule Self-Assembled Monolayers Suppress Smooth Muscle Cell Proliferation

A significant limitation of cardiovascular stents is restenosis, where excessive smooth muscle cell (SMC) proliferation following stent implantation causes blood vessel reocclusion. While drug-eluting stents minimize SMC proliferation through releasing cytotoxic or immunosuppressive drugs from polymer carriers, significant issues remain with delayed healing, inflammation, and hypersensitivity reactions associated with drug and polymer coatings. Amphiphilic macromolecules (AMs) comprising a sugar-based hydrophobic domain and a hydrophilic poly­(ethylene glycol) tail are noncytotoxic and recently demonstrated a concentration-dependent ability to suppress SMC proliferation. In this study, we designed a series of AMs and studied their coating properties (chemical composition, thickness, grafting density, and coating uniformity) to determine the effect of headgroup chemistry on bioactive AM grafting and release properties from stainless steel substrates. One carboxyl-terminated AM (<b>1cM</b>) and two phosphonate- (<b>Me-1pM</b> and <b>Pr-1pM</b>) terminated AMs, with varying linker lengths preceding the hydrophobic domain, were grafted to stainless steel substrates using the tethering by aggregation and growth (T-BAG) approach. The AMs formed headgroup-dependent, yet uniform, biocompatible adlayers. <b>Pr-1pM</b> and <b>1cM</b> demonstrated higher grafting density and an extended release from the substrate over 21 days compared to <b>Me-1pM</b>, which exhibited lower grafting density and complete release within 7 days. Coinciding with their release profiles, <b>Me-1pM</b> and <b>1cM</b> coatings initially suppressed SMC proliferation in vitro, but their efficacy decreased within 7 and 14 days, respectively, while <b>Pr-1pM</b> coatings suppressed SMC proliferation over 21 days. Thus, AMs with phosphonate headgroups and propyl linkers are capable of sustained release from the substrate and have the ability to suppress SMC proliferation during the restenosis that occurs in the 3–4 weeks after stent implantation, demonstrating the potential for AM coatings to provide sustained delivery via desorption from coated coronary stents and other metal-based implants

Fluorescence studies of the SaB-BSA system coexisting with other components in SFDHI.

<p>Fluorescence studies of the SaB-BSA system coexisting with other components in SFDHI.</p

Docking orienations of SaB for binding on BSAand HSA.

<p>Docking orienations of SaB for binding on BSAand HSA.</p

Results for Site marker competitive experiments.

<p>Results for Site marker competitive experiments.</p

The calculated fluorescence parameters of single tested component with BSA, at 310 K and pH 7.2.

<p>The calculated fluorescence parameters of single tested component with BSA, at 310 K and pH 7.2.</p

Modified Stern-Volmer plots of SaB-BSA system andHYSA-BSA system.

<p>Modified Stern-Volmer plots of SaB-BSA system andHYSA-BSA system.</p

Binding parameters of SaB-BSA system in the absence and presence of SFDHI, at 310 K, pH 7.2.

<p>K’_b is the K_b of SaB-BSA system in the presence of coexisted components.</p><p>Binding parameters of SaB-BSA system in the absence and presence of SFDHI, at 310 K, pH 7.2.</p

Chemical structures of HSAand BSA.

<p>Chemical structures of HSAand BSA.</p

Binding parameters of competitive experiments of SaB-BSA system, at 310 K, pH 7.2.

<p>Binding parameters of competitive experiments of SaB-BSA system, at 310 K, pH 7.2.</p

Modified Scatchard plos of SaB-BSA system and HYSA-BSA system.

<p>Modified Scatchard plos of SaB-BSA system and HYSA-BSA system.</p