Interactive Hemocompatible Nanocoating to Prevent Surface‐Induced Coagulation in Medical Devices

Abstract

Interfacing blood with any artificial surface instantly triggers the activation of coagulation at the interface, posing a risk of adverse thromboembolic complications. Immediately upon contact, blood proteins adsorb to the surface turning it into an active prothrombogenic and proinflammatory interface promoting the activation of platelets and the coagulation cascade. Here, an interactive hemocompatible nanocoating is designed that synergistically combines antifouling polymer brushes with the activity of an anti‐FXIIa antibody to tackle the two main causes of surface‐induced coagulation. The brushes provide a passive layer rendering the surface stealth and non‐thrombogenic against blood activation. Furthermore, as soon as traces of FXIIa arise, the coating immediately and specifically scavenges it, thus actively switching‐off contact activation right at the beginning. Moreover, a means is developed to translate this coating to a broad range of polymeric surfaces commonly used in medical devices. The coated surfaces prevent protein adsorption and provide a barrier to bacterial colonization while being capable of capturing biologically relevant concentrations of FXIIa. Notably, the coating completely prevents the formation of clots on the surface when exposed to blood. Thus, the interactive anti‐FXIIa nanocoating provides a new avenue to improve the hemocompatibility of medical devices in a safe and efficient manner.

A guide to functionalisation and bioconjugation strategies to surface-initiated polymer brushes

“…45,194,211 Recently, a biosensing platform for detection of SARS-CoV-2 was also proposed based on antibodies conjugated to poly(N-(2-hydroxypropyl) methacrylamide)-r-poly(carboxybetaine methacrylamide)-r-poly(sulfobetaine methacrylamide) brushes, using the same EDC/NHS functionalisation strategy. 56 This approach has also found application for the coupling of proteins involved in the breakdown of blood clots 57 and antibodies recognising the coagulation Factor XII (FXIIa) 227 for hemocompatible coatings design. Similarly, IgG antibodies were coupled to terpolymer brushes via EDC/NHS and displayed surface densities in the range of 150-220 ng cm À2 .…”

Synthetic Evolution of a Supramolecular Harpooning Mechanism to Immobilize Vesicles at Antifouling Interfaces

“…Arguably, BP is the most challenging bodily fluid as it contains a high concentration of proteins of varying charge and hydrophilicity as well as extracellular vesicles, and lipids. Moreover, some of the proteins may have a high affinity for surfaces and act directly as activators (FXIIa, complement C3) [53,81] or indirectly as a helper for the adhesion of other proteins. [82] The controls poly(HPMA) brushes and the poly(HPMA-co-BPMAA) surface-attached hydrogel prevented the fouling almost completely (Γ BP = 3 ng cm −2 and Γ BP = 4 ng cm −2 respectively).…”

Tackling the Root Cause of Surface‐Induced Coagulation: Inhibition of FXII Activation to Mitigate Coagulation Propagation and Prevent Clotting

“…In this work, we grafted poly(HPMA-co-CBMAA) brushes having 85% of the first comonomer and 15% of the second comonomer. These brushes have been previously shown to have excellent repellency to plasma protein, [46,47] a prerequisite to build hemo-compatible surfaces that do not activate the contact system due to conformational changes of the adsorbed proteins signaling to coagulation factors or platelets. Additionally, the copolymer was selected to allow functionalization of the brushes through the carboxyl group of CBMAA, while not interfering with the overall antifouling behavior of the brushes stemming from both, HPMA and CBMAA.…”

“…[37,38] Moreover, polymer brushes made from, e.g., carboxybetaines exhibit kosmotropic groups, which prevent conformational changes of proteins, [39][40][41][42][43][44][45] allowing their functionalization with enzymes or their inhibitors. [46][47][48] The modulatory level is designed by functionalization of the passive level with C1INH, which was shown to reduce FXII activation in previous work. [49] C1INH on the surface leads to local capture and deactivation of 𝛽-FXIIa and PK, the promoters of surface-induced coagulation.…”

“…As previously described, the antifouling poly(HPMA-co-CBMAA) brushes prohibit fouling from blood plasma (BP) and FXII. [46,47] The immobilization of C1INH will improve the hemocompatibility, while the capturing of 𝛽-FXIIa and PK do not interfere with the overall hemostasis. The translation of nature's blueprints to regulate the activation of FXII to a nonthrombogenic surface is a promising approach to enhancing the hemocompatibility of blood-contacting medical devices.…”