The
emergence of “superbugs” is not only problematic
and potentially lethal for infected subjects but also poses serious
challenges for the healthcare system. Although existing antibacterial
agents have been effective in some cases, the side effects and biocompatibility
generally present difficulties. The development of new antibacterial
agents is therefore urgently required. In this work, we have adapted
a strategy for the improvement of poly(hexamethylene guanidine) hydrochloride
(PHMG), a common antibacterial agent. This involves copolymerization
of separate monomer units in varying ratios to find the optimum ratio
of the hydrocarbon to guanidine units for antibacterial activity.
A series of these copolymers, designated as PGB, was synthesized.
By varying the guanidine/hydrophobic ratio and the copolymer molecular
weight, a structure-optimized PGB was identified that showed broad-spectrum
antibacterial activity and excellent biocompatibility in solution.
In an antibacterial assay, the copolymer with the optimum composition
(hydrophobic unit content 25%) inhibited >99% Staphylococcus
aureus and was compatible with mammalian cells. A
polyurethane emulsion containing this PGB component formed transparent,
flexible films (PGB-PU films) on a wide range of substrate surfaces,
including soft polymers and metals. The PGB-PU films showed excellent
bacteriostatic efficiency against nosocomial drug-resistant bacteria,
such as Pseudomonas aeruginosa and
methicillin-resistant S. aureus (MRSA).
It is concluded that our PGB polymers can be used as bacteriostatic
agents generally and in particular for the design of antibacterial
surfaces in medical devices.
Heparin-mimicking polymers have emerged as an alternative to heparin to construct effective and safe anticoagulant surfaces. However, the present heparin-mimicking polymers are usually limited to the combinations of glucose and sulfonic acid units, and the structure origin of their anticoagulant properties remains vague. Inspired by the structure of natural heparin, we synthesized a series of novel heparin-mimicking polymers (named GSAs) composed of three units, glucose, sulfonic acid, and carboxylic acid. Then, we constructed artificial extracellular matrices composed of GSAs and two typical cationic polymers, polyethyleneimine and chitosan, to investigate the anticoagulation and endothelialization of GSAs. By changing the ratio of the three units, their functions in the matrices were studied systematically. We found that an increase in the sulfonic acid content enhanced surface anticoagulant activity, an increase in glucose and sulfonic acid content promoted the proliferation of human umbilical vein vascular endothelial cells, and an increase in the carboxylic acid content inhibited the adherence of human umbilical vein vascular smooth muscle cells. This work uncovers the important role of the GSAs structure to the anticoagulation properties, which sheds new light on the design and preparation of heparin-mimicking polymers for practical engineering applications.
The overuse of antibiotics has triggered a new infection crisis, and natural antimicrobial peptides (AMPs) have been extensively studied as an alternative to fight microorganisms. Polypeptoids, or polypeptide-biomimetics, offer similar...
In analogy with adsorbed protein films, we have fabricated a family of 2D nanofilms composed of poly(N-vinyl caprolactam-co-vinylimidazole) (PNVCL) nanogels. NVCL was copolymerized with 1-vinylimidazole (VIM), then cross-linked with α,ω-dibromoalkanes...
Anticoagulant
surface modification of blood-contacting materials
has been shown to be effective in preventing thrombosis and reducing
the dose of anticoagulant drugs that patients take. However, commercially
available anticoagulant coatings, that is, both bioinert and bioactive
coatings, are typically based on a single anticoagulation strategy.
This puts the anticoagulation function of the coating at risk of failure
during long-term use. Considering the several pathways of the human
coagulation system, the synergy of multiple anticoagulation theories
may provide separate, targeted effects at different stages of thrombosis.
Based on this presumption, in this work, negatively charged poly(sodium p-styrenesulfonate-co-oligo(ethylene glycol)
methyl ether methacrylate) and positively charged poly(lysine-co-1-adamantan-1-ylmethyl methacrylate) were synthesized
to construct matrix layers on the substrate by electrostatic layer-by-layer
self-assembly (LBL). Amino-functionalized β-cyclodextrin (β-CD-PEI)
was subsequently immobilized on the surface by host–guest interactions,
and heparin was grafted. By adjusting the content of poly(oligo(ethylene
glycol) methyl ether methacrylate) (POEGMA), the interactions between
modified surfaces and plasma proteins/cells were regulated. This multistage
anticoagulant surface exhibits inertness at the initial stage of implantation,
resisting nonspecific protein adsorption (POEGMA). When coagulation
reactions occur, heparin exerts its active anticoagulant function
in a timely manner, blocking the pathway of thrombosis. If thrombus
formation is inevitable, lysine can play a fibrinolytic role in dissolving
fibrin clots. Finally, during implantation, endothelial cells continue
to adhere and proliferate on the surface, forming an endothelial layer,
which meets the blood compatibility requirements. This method provides
a new approach to construct a multistage anticoagulant surface for
blood-contacting materials.
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