Poly(phosphorylcholine) (PPC), which mimics zwitterionic phosphorylcholine moieties outside cell membranes, has been extensively studied and used as a biomimetic fouling-resistant material in many applications over the past decades ( 12).
Blood bowl 2 fouling series#
In recent decades, zwitterionic materials that contain an equal number of oppositely charged ions (zwitterions) have been emerging as a new series of hydrophilic biomaterials for nonfouling purposes as they can strongly hold water molecules via electrostatically induced hydration ( 10, 11). As any nonspecific interaction moieties can be detected by the immune system, the hydrophobic character of PEG would be amplified under in vivo conditions, particularly when it is conjugated with highly immunogenic proteins, generating PEG-specific antibodies ( 8, 9). Although commonly considered hydrophilic, PEG containing a hydrophobic C─C backbone along with a hydrophobic −O(CH 3) terminal group is amphiphilic, as evidenced by its good solubility in many organic solvents in addition to water. The attachment of PEG to surfaces, known as “PEGylation,” has been a “gold standard” strategy to resist nonspecific protein adsorption. Poly(ethylene glycol) (PEG) is the most widely used stealth material. At present, there are few highly hydrophilic materials that can meet the nonfouling demand of practical applications, particularly in complex biological media. However, the hydration capability of most hydrophilic materials is often not sufficient to produce a nonfouling surface. These materials have been shown to create a hydration shell that repels biomolecules or cells from contacting surfaces, making the underlying substrates “stealthy” ( 7). To achieve a nonfouling surface, a number of hydrophilic materials have been used, where the surface hydration plays a pivotal role ( 6). Therefore, reducing or eliminating undesirable “biofouling” is of paramount importance to the safety and function of medical devices or drugs. Likewise, drug-delivering carriers are also susceptible to the nonspecific attachment of proteins and cells, which may result in the rapid clearance of therapeutic drugs and adverse immune responses ( 4, 5). As a result, a variety of iatrogenic complications including inflammation, infection, tissue fibrosis, and capsulate formation will be triggered, leading to the failure of biomaterials. For example, biomaterials tend to be covered with a layer of host proteins shortly after implantation, which thereafter will provoke an irrevocable foreign body reaction (FBR) ( 2, 3). Unwanted adsorption of biomolecules, cells, and microorganisms represents a great challenge in many applications from medical devices to drug delivery systems ( 1, 2). The discovery of PTMAO polymers demonstrates the power of molecular understanding in the design of new biomimetic materials and provides the biomaterials community with another class of nonfouling zwitterionic materials. The mechanism accounting for the extraordinary hydration of PTMAO was elucidated by molecular dynamics simulations.
The nonfouling properties of PTMAO were demonstrated under highly challenging conditions. Inspired by trimethylamine N-oxide (TMAO), a zwitterionic osmolyte and the most effective protein stabilizer, we here report TMAO-derived zwitterionic polymers (PTMAO) as a new class of ultralow fouling biomaterials. Unfortunately, there are only three major classes of zwitterionic materials based on poly(phosphorylcholine), poly(sulfobetaine), and poly(carboxybetaine) currently available. Zwitterionic polymers emerge as a class of highly effective ultralow fouling materials due to their superhydrophilicity, outperforming other hydrophilic materials such as poly(ethylene glycol). However, few are able to achieve ultralow fouling in complex biological milieu. Materials that resist nonspecific protein adsorption are needed for many applications.
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