Thermoresponsive Heparin Bioconjugate as Novel Aqueous Antithrombogenic Coating Material

Abstract

A novel thermoresponsive aqueous antithrombogenic coating material comprising a heparin bioconjugate with a six-branched, star-shaped poly(2-(dimethylaminoethyl)methacrylate) (6B-PDMAEMA), which has both thermoresponsive and cationic characters, was developed to reduce the thrombogenic potential of blood-contacting materials such as synthetic polymers or tissue-engineered tissues in cardiovascular devices. 6B-PDMAEMA with M(n) of ca. 24 kDa was designed as a prototype compound by initiator-transfer agent-terminator (iniferter)-based living radical photopolymerization from hexakis(N,N-diethyldithiocarbamylmethyl)benzene. Bioconjugation of heparin with 6B-PDMAEMA occurred as soon as both aqueous solutions were simply mixed to form particles. The particle size at 25 °C was less than several hundred nanometers in diameter under a heparin/6B-PDMAEMA mixing weight ratio of over 2.5. The particles were very stable because of the prevention of hydrolysis of 6B-PDMAEMA in its bioconjugated form. Because the lower critical solution temperature of the bioconjugate ranges from approximately 20 to 36 °C for the formation of microparticles, the coating could be done in an aqueous solution at low temperatures. The excellent adsorptivity and high durability of the coating above 37 °C was demonstrated on silicone and polyethylene films by surface chemical compositional analysis. Blood coagulation was significantly reduced on the bioconjugate-coated surfaces. Therefore, the thermoresponsive bioconjugate developed here appears to satisfy the initial requirements for a biocompatible aqueous coating material.

Enhanced Transfection Efficiency of Poly(N,N-dimethylaminoethyl methacrylate)-Based Deposition Transfection by Combination with Tris(hydroxymethyl)aminomethane

“…In addition to its cationic properties, PDMAEMA is also a thermoresponsive polymer with a low LCST that ranges from 34 to 37 °C. 21 This unique combination of properties makes PDMAEMA suitable for bioconjugation with DNA for polyplex formation and amenable to conversion to a water-insoluble form for deposition of polyplexes on a culture dish surface. However, very little biomedical research has been carried out on the dual characteristics of this polymer.…”

Amphiphilic Core Cross-Linked Star Polymers for the Delivery of Hydrophilic Drugs from Hydrophobic Matrices

“…21 However, its hydrophilic nature makes incorporation into hydrophobic matrices difficult, thereby requiring a delivery vehicle to increase loading and to allow prolonged delivery. Although numerous nano-and microparticle drug delivery systems have been studied for heparin release, including reverse micelles, 22 bioconjugates, 23,24 liposomes, 25 nanospheres, 26 and dendrimers, 27,28 few studies have examined the development of carriers for the loading of hydrophilic drugs (i.e., heparin) into bulk hydrophobic materials for sustained release. In this work, we propose that an amphiphilic star polymer with a hydrophilic core will promote drug loading while the hydrophobic arms will improve integration into the hydrophobic polymer matrix, a long-standing challenge in the synthesis of polymer−nanoparticle composites.…”

“…However, its hydrophilic nature makes incorporation into hydrophobic matrices difficult, thereby requiring a delivery vehicle to increase loading and to allow prolonged delivery. Although numerous nano- and microparticle drug delivery systems have been studied for heparin release, including reverse micelles, bioconjugates, , liposomes, nanospheres, and dendrimers, , few studies have examined the development of carriers for the loading of hydrophilic drugs ( i.e. , heparin) into bulk hydrophobic materials for sustained release.…”

Host Responses to Biomaterials and Anti‐Inflammatory Design—a Brief Review

“…Furthermore, biomolecule strategies by decoration biomaterials with endogenously expressed proteins to modulate the immune system are gaining considerable interests recently . The bioactive molecules include ECM proteins, cell membrane proteins, or cytokines that can directly interact with immune cells, as well as proteins that indirectly modulate immune cells by preventing complement and coagulation activation (Figure C). In addition, biomaterials decorated with such biomolecules are closer to the natural environment of cells and may enable more specific interactions.…”