Ultrathin Zwitterionic Polymer Coatings to Improve Hemocompatibility of Silicon-based Implantable Medical Devices
Silicon-based bio-microelectromechanical systems (bioMEMS) have become increasingly attractive for medical implants due to their relative low cost and capacity for fabrication of intricate micro- and nanofeatures. However, when silicon surfaces encounter blood, device failure can occur as plasma proteins adhere to the surface and the coagulation cascade is activated leading to thrombosis. Modifying silicon surfaces with hemocompatible coatings may reduce protein adsorption and platelet activation, increasing the lifetime of the implant.
Using bioMEMS technology, our group has developed silicon nanopore membranes (SNMs) for application in bioartificial organs. Highly uniform pores of controllable size make SNMs attractive for immunoisolation and blood filtration. To improve hemocompatibility of SNMs, this dissertation investigates sub-5 nm biomimetic polymer surface coatings. Specifically, two ultrathin zwitterionic coatings, poly(sulfobetaine methacrylate) (pSBMA) and poly(2-methacryloyloxyethyl phosphorylcholine) (pMPC), were developed and characterized via x-ray photoelectron spectroscopy, contact angle, atomic force microscopy and ellipsometry. The coatings were tested under biological shear conditions and after exposure to five standard sterilization methods. Anti-fouling and hemocompatible characteristics of the coatings were evaluated by measuring protein adsorption from single protein solutions of human serum albumin and fibrinogen, and examining platelet activation after exposure to fresh human blood and implantation in porcine model for up to 26 days.
Characterization results showed successful sub-5 nm pSBMA and pMPC surface modifications. In this thickness range, SNMs remained patent and modified silicon substrates resisted bio-fouling from single protein solutions of human albumin and fibrinogen, with pSBMA reducing protein adsorption by >80% compared to uncoated silicon. Shear data suggests the coatings are robust and functional following shear rates up to 2000/s over 24 hours. Additionally, they withstood sterilization procedures, with best performance of pSBMA and pMPC after electron-beam sterilization and ethylene oxide gas treatment, respectively. Scanning electron microscopy and immunohistochemistry following exposure to fresh human blood flow demonstrated pSBMA-silicon reduced platelet adhesion and activation by >97%. Porcine implants with pSBMA-silicon substrates remained patent over 26 days, with no gross clots in the flow path and minimal presence of blood activation. These promising in vitro and in vivo results will lead to further studies coupling SNM filtration and surface coatings, as well as clinical testing to determine the human response for use in bioartificial kidney and pancreas device applications.