This review summarizes recent research on the design of polymer material systems based on biomimetic concepts and reports on the medical devices that implement these systems. Biomolecules such as ...proteins, nucleic acids, and phospholipids, present in living organisms, play important roles in biological activities. These molecules are characterized by heterogenic nature with hydrophilicity and hydrophobicity, and a balance of positive and negative charges, which provide unique reaction fields, interfaces, and functionality. Incorporating these molecules into artificial systems is expected to advance material science considerably. This approach to material design is exceptionally practical for medical devices that are in contact with living organisms. Here, it is focused on zwitterionic polymers with intramolecularly balanced charges and introduce examples of their applications in medical devices. Their unique properties make these polymers potential surface modification materials to enhance the performance and safety of conventional medical devices. This review discusses these devices; moreover, new surface technologies have been summarized for developing human-friendly medical devices using zwitterionic polymers in the cardiovascular, cerebrovascular, orthopedic, and ophthalmology fields.
For long-lasting artificial hip joint implants, it is necessary to reduce the wear of the acetabular liner composed of ultra-high-molecular-weight polyethylene (UHMWPE) and to eliminate ...periprosthetic osteolysis. An articular cartilage-mimicking technology has been developed for nanoscale surface modification by grafting poly(2-methacryloyloxyethyl phosphorylcholine) (MPC) onto a highly cross-linked UHMWPE (X-UHMWPE) using photoinduced polymerization. The thickness of the poly(MPC) graft layer is 100-200 nm. This treatment increases the surface hydrophilicity. Other hydrophilic polymers grafted onto the X-UHMWPE are not suitable for long-term functioning under biological conditions. Studies of the tribological and biological effects with poly(MPC) grafted onto the X-UHMWPE substrate revealed that this grafting decreases the production of wear particles and bone resorption responses. The poly(MPC)-grafted X-UHMWPE has been introduced onto an artificial hip joint as a liner for lubrication. This artificial hip joint has been used clinically since 2011 and has been implanted in more than 20 000 patients. This technology has also been applied to the surface modification of PMPC on poly(ether ether ketone) (PEEK), using self-initiated photoinduced grafting, for the development of a new type of artificial joint. This articular cartilage-mimicking technology, which is applied to obtain highly lubricating surfaces, is therefore suitable for preparing artificial hip joint substrates.
This review article describes fundamental aspects of cell membrane-inspired phospholipid polymers and their usefulness in the development of medical devices. Since the early 1990s, polymers composed ...of 2-methacryloyloxyethyl phosphorylcholine (MPC) units have been considered in the preparation of biomaterials. MPC polymers can provide an artificial cell membrane structure at the surface and serve as excellent biointerfaces between artificial and biological systems. They have also been applied in the surface modification of some medical devices including long-term implantable artificial organs. An MPC polymer biointerface can suppress unfavorable biological reactions such as protein adsorption and cell adhesion - in other words, specific biomolecules immobilized on an MPC polymer surface retain their original functions. MPC polymers are also being increasingly used for creating biointerfaces with artificial cell membrane structures.
For the acquisition of blood-compatible materials, various hydrophilic polymers for surface modification have been examined. Among them, polymers with a representative phospholipid polar group, the ...phosphorylcholine (PC) group, are a successful example. These polymers were designed from inspiration of the cell membrane surface and provide protein adsorption resistance even following contact with plasma. This important property is based on the unique hydration state of water molecules surrounding hydrated polymer; in other words, water molecules weakly interact with the polymers and maintain their favorable cluster structure through hydrogen bonding. These polymers are not only hydrophilic, but also electrically neutral, important characteristics which make hydrogen bonding with water molecules less likely to occur and avoid hydrophobic interactions. Phosphorylcholine groups and other zwitterionic structures are significant as hydrophilic functional groups meeting these important requirements. In this review, blood compatibility of a polymer having a PC group is introduced in relation to its hydration structure, followed by a description of the applications of this polymer to cardiovascular medical devices.
Bioengineering with utilization of cells as one of the components of devices has been expected to advance developments of medical and pharmaceutical technologies. When cells are engineered, it is ...important to establish means for maintaining the activity of the cells, enhancing cell functions, and controlling cell responses. This review summarizes researches for cell encapsulation using synthetic phospholipid polymers composed of 2-methacryloyloxyethyl phosphorylcholine unit, which make hydrogel spontaneously in a cell culture environment and then cells are preserved in situ. The phospholipid polymer hydrogels show no adverse effects on the cell culture process and the mechanical properties of the hydrogels can regulate for controlling the function of cells. It also introduces molecular designs that can be easily recovered from the hydrogel matrix after the encapsulated cells have differentiated. Furthermore, the application of these hydrogels to a microdevice also describes advanced utilization of cultured cells. Phospholipid polymer hydrogels can exhibit its function even when they are applied in vivo, and as one application, introduces the prevention of adhesion with other tissues in the tissue healing process. That is, the potential application of the phospholipid polymer hydrogels in cell engineering are described.
2-Methacryloyloxyethyl phosphorylcholine (MPC) is methacrylate bearing a phosphorylcholine group in the side chain. The phosphorylcholine group generates several unique properties arising from its ...zwitterionic structure, consisting of a phosphate anion and a trimethylammonium cation. Despite these charged groups, the total electrical charge of the species is zero because of the formation of an inner salt. The polymerization of MPC proceeds both conventional and living radical polymerizations. And, using these method, the corresponding polymer can be obtained efficiently. The product, poly(MPC), is soluble in aqueous media, even if the ionic strength of the solution is high, such as in the presence of 5.0 mol/L NaCl. The polymer does not show any surface active properties, even when the polymer concentration is greater than 1.0 g/dL. Hydration of poly(MPC) mainly occurs by hydrophobic hydration of the three methyl groups in the trimethylammonium group. Thus, this hydration induces an increase in a clathrate cage structure of surrounding water molecules, i.e. an ice-like water state is formed. Because of this unique hydration, poly(MPC) cannot make strong interactions with proteins and cells. Some biomedical applications have used poly(MPC) as a protein and solid-surface modification agents.
To investigate the effect of antibody orientation on its immunological activities, we developed a novel and versatile platform consisting of a well-defined phospholipid polymer surface on which ...staphylococcal protein A (SpA) was site-selectively immobilized. The application of a biocompatible phospholipid-based platform ensured minimal denaturation of immobilized antibodies, and the site-selective immobilization of SpA clarified the effect of antibody orientation on immunological activities. The phospholipid polymer platform was prepared on silicon substrates using the surface-initiated atom transfer radical polymerization (SI-ATRP) technique. An enzymatic reaction was performed for orientation-selective coupling of SpA molecules to the polymer brush surface. Orientation-controlled antibodies were achieved using enzymatic reactions, and these antibodies captured 1.8 ± 0.1 antigens on average, implying that at least 80% of immobilized antibodies reacted with two antigens. Theoretical multivalent binding analysis further revealed that orientation-controlled antibodies had antigen−antibody reaction equilibrium dissociation constants (K d) as low as 8.6 × 10−10 mol/L, whereas randomly oriented and partially oriented antibodies showed K d values of 2.0 × 10−7 and 1.2 × 10−7 mol/L, respectively. Strict control of antibody orientation not only formed an approximately 100-fold stronger antigen−antibody complex than the controls but also sustained the native antibody K d (10−10−10−9 mol/L). These findings support the significance of antibody orientation because controlling the orientation resulted in high reactivity and theoretical binding capacity.
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•Polymer brush surfaces were suitable for analyzing protein adsorption force.•Fibronectin adsorption depended on the chemical structure of polymer.•Conformation change of fibronectin ...adsorbed was important for inducing cell adhesion.•Zwitterionic polymer could prevent both protein adsorption and cell adhesion.•Cationic polymer brush surface inhibited cell proliferation.
The effects of protein adsorption on the polymer brush surfaces with well-defined chemical structures and physical properties were examined with respect to initial protein adsorption, structural changes to the adsorbed proteins, and subsequent cell adhesion. Four polymer brush surfaces with different hydrophilicities and charge states were prepared. The molecular interaction forces during adsorption-desorption processes of protein on the polymer brush surfaces depending on the chemical structure of the polymer were determined. Crucially, these molecular interactions affected the adsorption behavior and structural changes of fibronectin (FN), a cell-adhesive protein, used in this study. Adsorption of FN onto the zwitterionic polymer and anionic polymer surfaces was difficult, however significant protein adsorption to the hydrophobic and cationic surfaces was observed. Further, the structural changes to the adhered FN on these surfaces were significant. Subsequent cell adhesion experiments revealed that the adhered cell density was correlated with the amount of adsorbed FN and the degree of FN structural change. In addition, the cationic surface inhibited cell proliferation behavior. These results indicate that cellular responses can be indirectly regulated by controlling the molecular interactions which induced the structural change of adsorbed proteins via the material surface properties.
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