Blood compatible materials are required for a wide variety of medical devices. Despite many years of intensive effort, however, the blood compatibility problem, in particular the ability to prevent thrombosis, remains unsolved. Based on the knowledge that the vascular endothelium, the ultimate blood contacting surface, draws on several mechanisms to maintain blood fluidity, it seems reasonable that analogous multifunctionality should be the goal for blood compatible biomaterials. In the present work, a polyurethane surface was modified with the terpolymer poly(2-hydroxyethyl methacrylate-co-6-amino-2-(2-methacylamido)-hexanoic acid-co-1-adamantan-1-ylmethyl methacrylate) (poly(HEMA-co-LysMA-co-AdaMA)), referred to as PU-PHLA. Poly(HEMA) and poly(LysMA) were intended to provide, respectively, resistance to non-specific protein adsorption and the ability to lyse incipient clots. The heparin-like moiety, sulfonated β-cyclodextrin was immobilized on the PU-PHLA via host–guest interactions with the poly(AdaMA). This component is expected to inhibit coagulation and smooth muscle cell proliferation and to promote endothelialization. The resulting materials were shown to have multifunctionalities including fibrinolytic activity, anticoagulant activity and the ability to promote endothelial cell adhesion and inhibit smooth muscle cell adhesion. This work provides a new strategy for the development of multifunctional, endothelial-mimicking, biomaterials for blood contacting applications.

Thrombus formation remains a serious problem in developing blood compatible materials. Despite continuous, intensive efforts over many years to prepare surfaces that prevent clotting, such surfaces have not been achieved; indeed it seems that surface-induced clotting is inevitable. An alternative approach is to accept that clotting will occur and to design surfaces so that small, nascent clots will be lysed before they can cause harm. The generation of plasmin, as in the fibrinolytic system, may be adopted for this purpose. The vascular endothelium (the inner surface of intact blood vessels) releases nitric oxide (NO) on a continuous basis. NO protects against platelet activation and aggregation, and also has an anti-proliferative effect on smooth muscle cells (SMCs). Based on these two important functions of the vascular system, the approach of constructing a fibrinolytic surface that generates NO is developed in the present work. Poly(oligo(ethylene glycol) methyl ether methacrylate-co-6-amino-2-(2-methacylamido)-hexanoic acid) (poly(OEGMA-co-LysMA)) was attached to a vinyl-functionalized polyurethane (PU) surface by graft polymerization giving a surface (PU-POL) with protein-resistant properties (via poly(OEGMA)) and clot lysing properties (via poly(LysMA)). Selenocystamine, which catalyzes S-nitrosothiol decomposition to generate NO in the vasculature, was then immobilized on the PU-POL surface via covalent attachment. A dual functioning surface with fibrinolytic activity (lysis of nascent clots) and NO releasing ability (inhibition of platelet adhesion and SMC adhesion as well as proliferation) was thereby constructed.

•The mechanism of GAGs regulating stem cell differentiation is discussed.•Various GAG-based materials that induce stem cell differentiation are summarized.•GAG-mimetic materials that influence stem cell differentiation are categorized.Glycosaminoglycans (GAGs) are linear sulfated polysaccharides that exist in most mammalian cells. By undergoing conjugation with various proteins, GAGs play important roles in a variety of bioactivities, including promoting stem cell differentiation. However, they have their own intrinsic disadvantages that limit their further applications for cell therapy and tissue engineering. Therefore, more and more GAG-mimetic materials have been studied as natural GAG analogs for emerging applications. This review explains the mechanism of how GAGs regulate stem cell differentiation and elaborates on the current progress of the applications of GAG-based materials on regulating stem cell differentiation. The types and applications of GAG-mimetic materials on regulating stem cell differentiation are introduced as well. Finally, the challenges and perspectives for GAGs and their mimetics in regulating stem cell differentiation are discussed.Download high-res image (235KB)Download full-size image

For potential applications in the isolation and enrichment of circulating tumor cells (CTCs), we have developed gold nanoparticle layers (GNPLs) of different roughness modified with TD05 aptamers (GNPL-APT). In serum-free binary cell mixtures containing Ramos cancer cells and CEM cells, the density of Ramos cells adherent to highly rough GNPL-APT was 19 times that of CEM cells. However, in serum-containing conditions, the specificity of GNPL-APT for Ramos cells was much reduced. To improve Ramos specificity in the presence of serum, we attached the TD05 aptamer to the layers via poly(oligo(ethylene glycol) methacrylate) (POEGMA) as an antifouling spacer (GNPL-POEGMA-APT). In serum-containing environment GNPL-POEGMA-APT showed an enhanced selectivity for Ramos cells, which increased with increasing surface roughness. The results of this study indicate that surfaces combining appropriate chemical composition and micro/nano roughness structures may be useful for cell separation, including the isolation of cancer cells for diagnosis.Keywords: aptamer; cancer cells; selective capture; serum; surface roughness;

Thrombus formation remains a serious problem in developing blood compatible materials. Despite continuous, intensive efforts over many years to prepare surfaces that prevent clotting, such surfaces have not been achieved; indeed it seems that surface-induced clotting is inevitable. An alternative approach is to accept that clotting will occur and to design surfaces so that small, nascent clots will be lysed before they can cause harm. The generation of plasmin, as in the fibrinolytic system, may be adopted for this purpose. The vascular endothelium (the inner surface of intact blood vessels) releases nitric oxide (NO) on a continuous basis. NO protects against platelet activation and aggregation, and also has an anti-proliferative effect on smooth muscle cells (SMCs). Based on these two important functions of the vascular system, the approach of constructing a fibrinolytic surface that generates NO is developed in the present work. Poly(oligo(ethylene glycol) methyl ether methacrylate-co-6-amino-2-(2-methacylamido)-hexanoic acid) (poly(OEGMA-co-LysMA)) was attached to a vinyl-functionalized polyurethane (PU) surface by graft polymerization giving a surface (PU-POL) with protein-resistant properties (via poly(OEGMA)) and clot lysing properties (via poly(LysMA)). Selenocystamine, which catalyzes S-nitrosothiol decomposition to generate NO in the vasculature, was then immobilized on the PU-POL surface via covalent attachment. A dual functioning surface with fibrinolytic activity (lysis of nascent clots) and NO releasing ability (inhibition of platelet adhesion and SMC adhesion as well as proliferation) was thereby constructed.

Blood compatible materials are required for a wide variety of medical devices. Despite many years of intensive effort, however, the blood compatibility problem, in particular the ability to prevent thrombosis, remains unsolved. Based on the knowledge that the vascular endothelium, the ultimate blood contacting surface, draws on several mechanisms to maintain blood fluidity, it seems reasonable that analogous multifunctionality should be the goal for blood compatible biomaterials. In the present work, a polyurethane surface was modified with the terpolymer poly(2-hydroxyethyl methacrylate-co-6-amino-2-(2-methacylamido)-hexanoic acid-co-1-adamantan-1-ylmethyl methacrylate) (poly(HEMA-co-LysMA-co-AdaMA)), referred to as PU-PHLA. Poly(HEMA) and poly(LysMA) were intended to provide, respectively, resistance to non-specific protein adsorption and the ability to lyse incipient clots. The heparin-like moiety, sulfonated β-cyclodextrin was immobilized on the PU-PHLA via host–guest interactions with the poly(AdaMA). This component is expected to inhibit coagulation and smooth muscle cell proliferation and to promote endothelialization. The resulting materials were shown to have multifunctionalities including fibrinolytic activity, anticoagulant activity and the ability to promote endothelial cell adhesion and inhibit smooth muscle cell adhesion. This work provides a new strategy for the development of multifunctional, endothelial-mimicking, biomaterials for blood contacting applications.