Water-soluble Phospholipid Polymer Research Articles

Effect of liposome surface modification with water-soluble phospholipid polymer chain-conjugated lipids on interaction with human plasma proteins.

Alternative liposome surface coatings for PEGylation to evade the immune system, particularly the complement system, have garnered significant interest. We previously reported poly(2-methacryloyloxyethyl phosphorylcholine) (MPC)-based lipids (PMPC-lipids) and investigated the surface modification of liposomes. In this study, we synthesize PMPC-lipids with polymerization degrees of 10 (MPC10-lipid), 20 (MPC20-lipid), 50 (MPC50-lipid), and 100 (MPC100-lipid), and coated liposomes with 1, 5, or 10 mol% PMPC-lipids (PMPC-liposomes). Non-modified and PEGylated liposomes are used as controls. We investigate the liposome size, surface charge, polydispersity index, and adsorption of plasma proteins to the liposomes post incubation in human plasma containing N,N,N',N'-ethylenediamine tetraacetic acid (EDTA) or lepirudin by some methods such as sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE), western blotting, and automated capillary western blot, with emphasis on the binding of complement protein C3. It is shown that the coating of liposome PMPC-lipids can suppress protein adsorption more effectively with an increase in the molecular weight and molar ratio (1-10 mol%). Apolipoprotein A-I is detected on PMPC-liposomes with a higher molecular weight and higher molar ratio of PMPC-lipids, whereas α2-macroglobulin is detected on non-modified, PEGylated, and PMPC-liposomes with a shorter polymer chain. In addition, a correlation is shown among the PMPC molecular weight, molar ratio, and C3 binding. The MPC10-lipid cannot inhibit C3 binding efficiently, whereas surface modifications with 10 mol% MPC20-lipid and 5 mol% and 10 mol% MPC50-lipid suppress both total protein and C3 binding. Hence, liposome modification with PMPC-lipids can be a possible strategy for avoiding complement activation.

Chemical Structural Effects of Amphipathic and Water-soluble Phospholipid Polymers on Formulation of Solid Dispersions.

For the polymeric carriers of solid dispersions, it is important that carriers themselves dissolve quickly and maintain the supersaturated state of amorphous drugs during their dissolution period to improve bioavailability. Amphipathic 2-methacryloyloxyethyl phosphorylcholine (MPC) polymers can be dissolved in water, owing to the extremely high hydrophilicity of the MPC units, and are used as an ideal feeder for drug molecules to form aggregates in aqueous conditions. We synthesized amphipathic MPC copolymers with different hydrophobic side chains and molar ratios of MPC units, and evaluated the effect of the polymers on dissolution rate and supersaturation maintenance of solid dispersions of indomethacin. In most of the water-soluble amphipathic MPC copolymers, "spring-parachute"-like dissolution behavior was observed, where the drug initially became supersaturated followed by slow precipitation. In particular, MPC copolymers with aromatic rings in their side chains or polymers with a high percentage of hydrophobic units remained in a supersaturated state for a longer period. In contrast, urethane groups, which form hydrogen bonds with drug molecules, could also interact with water and were not conducive to maintaining supersaturation. In addition, water solubility of the polymer is important for rapid dissolution.

Direct photoreactive immobilization of water-soluble phospholipid polymers on substrates in an aqueous environment

The purpose of this study is to achieve a simpler and safer surface modification of substrates using a photoreactive polymer in an aqueous environment. We synthesized water-soluble photoreactive polymers with both phenylazide groups and phosphorylcholine groups, poly(2-methacryloyloxyethyl phosphorylcholine-co-4-methacryl tetra(ethylene glycol)oxycarbonyl-4-phenylazide) (PMEPAz), via reversible addition fragmentation chain transfer polymerization. PMEPAz with different polymerization degrees were synthesized with a well-defined structure. To immobilize PMEPAz on the substrate surface by photoreaction, it is necessary to adsorb the polymer on the substrate surface in an aqueous solution because the phenylazide groups chemically bind to the substrate via a hydrogen abstract reaction. The relationship between the polymer solubilization state in the aqueous solution and the adsorption behavior at the surface was investigated. PMEPAz began to form unstable molecular aggregates at a concentration of 10−2 mg/mL and formed stable aggregates at 100 mg/mL. At a concentration of 10−1 mg/mL, unstable molecular aggregates of PMEPAz were formed in the aqueous solution, resulting in the maximization of the amount of adsorbed polymer and effective photoreaction with the substrate. The thickness of the reacted polymer layer on the substrate increased with an increase in the polymerization degree, a uniform polymer layer with a thickness of 3.4 nm was formed when the polymerization degree was 400. After surface modification, the hydrophobic surfaces of the original substrates became hydrophilic. Additionally, fibrinogen adsorption and platelet adhesion were effectively suppressed based on the characteristics of the phosphorylcholine unit.

Water-Soluble and Cytocompatible Phospholipid Polymers for Molecular Complexation to Enhance Biomolecule Transportation to Cells in Vitro.

Water-soluble and cytocompatible polymers were investigated to enhance a transporting efficiency of biomolecules into cells in vitro. The polymers composed of a 2-methacryloyloxyethyl phosphorylcholine (MPC) unit, a hydrophobic monomer unit, and a cationic monomer unit bearing an amino group were synthesized for complexation with model biomolecules, siRNA. The cationic MPC polymer was shown to interact with both siRNA and the cell membrane and was successively transported siRNA into cells. When introducing 20–50 mol% hydrophobic units into the cationic MPC polymer, transport of siRNA into cells. The MPC units (10–20 mol%) in the cationic MPC polymer were able to impart cytocompatibility, while maintaining interaction with siRNA and the cell membrane. The level of gene suppression of the siRNA/MPC polymer complex was evaluated in vitro and it was as the same level as that of a conventional siRNA transfection reagent, whereas its cytotoxicity was significantly lower. We concluded that these cytocompatible MPC polymers may be promising complexation reagent for introducing biomolecules into cells, with the potential to contribute to future fields of biotechnology, such as in vitro evaluation of gene functionality, and the production of engineered cells with biological functions.

Determination of association constants between water-soluble phospholipid polymer bearing phenylboronic acid group and polyol compounds for reversible formation of three-dimensional networks

To develop a reversible forming polymer network system, a polymer complexation was conducted between water-soluble and cytocompatible polymers, namely poly(2-methacryloyloxyethyl phosphorylcholine-co-n-butyl methacrylate-co-p-vinylphenylboronic acid) (PMBV) and poly(vinyl alcohol) (PVA). The two polymers spontaneously form hydrogel upon mixing. The association constant depended on the chemical structure of the polyol compounds and the aggregation of the PMBV. Compared to the association constants of PVA to PMBV, d-glucose and D-sorbitol have smaller and larger association constants, respectively, which is in good accord with the dissociation phenomenon of PMBV/PVA hydrogels. In conclusion, consideration of the association constants between the PMBV and polyol compounds is important for obtaining good reversibility of a polymer hydrogel system.

Solubilization and penetration enhancement of water-soluble and amphiphilic phospholipid polymer aggregate for poorly soluble drugs

Solubilization and penetration enhancement of water-soluble and amphiphilic phospholipid polymer aggregate for poorly soluble drugs

Enhanced stability of NADH/dehydrogenase mixture system by water-soluble phospholipid polymers

To maintain activity in a coenzyme/enzyme mixture system, such as β-nicotinamide adenine dinucleotide (NADH)/dehydrogenase, the water-soluble 2-methacryloyloxyethyl phosphorylcholine (MPC) polymers as an additive were synthesized and investigated for their stabilizing function. The inhibitor for the NADH/dehydrogenase reaction was spontaneously formed when the NADH was stored in the dehydrogenase solution. Therefore, we hypothesized that if the additive polymer could interact with an inhibitor without any adverse effect on the dehydrogenase, the activity in the NADH/dehydrogenase mixture could be maintained. We selected lactose dehydrogenase (LDH) as the enzyme, and the NADH was dissolved and incubated at 37°C in the LDH solution containing the polymers. The phospholipid polymers used in this study were poly(MPC) (PMPC), poly(MPC-co-3-trimethylammonium-2-hydroxypropyl methacrylate chloride) (PMQ) and poly[MPC-co-potassium 3-methacryloyloxypropyl sulfonate (MSO3)] (PMMSO3). The poly(MSO3) was used as a reference. For the PMQ and PMSO3 aqueous solutions, the activity of the NADH/LDH mixture system decreased with incubation time as the same level or lower than that in the Tris buffered solution in the absence of the polymers. However, for the poly(MPC-co-MSO3) (PMMSO3) aqueous solution, the activity of the NADH/LDH mixed system was six times higher than that in the buffered solution even after a 3-days incubation. The LDH activity was 1.5-1.8 times higher in the presence of the PMMSO3 compared with that in the PMSO3 solution. The mixture of two polymers, poly(MPC) and poly(MSO3), did not produce any stabilization. Thus, both the MPC and MSO3 units in the polymer chain had important and cooperative effects for stabilizing the NADH/LDH mixture.

Cytocompatible and spontaneously forming phospholipid polymer hydrogels

Given the importance of regulating living cell functions in three-dimensional (3D) environments, we have designed a cytocompatible and spontaneously forming polymer hydrogel matrix. Water-soluble phospholipid polymers bearing a phenylboronic acid unit, poly(2-methacryloyloxyethyl phosphorylcholine-co-n-butyl methacrylate-co-p-vinylphenylboronic acid) (PMBV), and poly(vinyl alcohol) (PVA), are candidate systems for preparing the hydrogel matrices. Aqueous solutions of PMBV and PVA can be used to form hydrogels based on reversible complexation between the phenylboronic acid groups in PMBV and the diol groups in PVA, even under cell culture conditions. Uniform cell encapsulation is easily achieved with hydrogel formation, and cells survived well in the hydrogel. By applying a spinning-assisted layer-by-layer (LbL) process, multilayered PMBV/PVA hydrogels containing living cells can be assembled. This multilayered hydrogel, which mimics the stratified structure of in vivo tissues, allows the layer-specific encapsulation of cells and temporary storage of bioactive molecules. Distance-dependent cell–cell interactions are investigated using the multilayered hydrogel where two cell-laden layers are separated by a finely controlled multilayered hydrogel. In addition, dual-crosslinked multilayered hydrogels are also assembled by alternative depositions of PMBV and photoreactive-PVA solutions, followed by photoirradiation. The dual-crosslinked hydrogel has a lower diffusivity of bioactive molecules than that of single-crosslinked hydrogel and therefore acts as a diffusion-controlling barrier. We demonstrate the utility of this dual-crosslinked hydrogel by examining ways to regulate the diffusion of bioactive molecules in the hydrogel and investigating the diffusion-dependent effects on cell behavior. In conclusion, these hydrogel matrices can provide insights into the regulation of cell behavior in 3D matrices. In turn, our results may contribute to the future design of 3D cell culture systems and tissue regenerated medicine based on cell engineering.

Redox-active cytocompatible phospholipid polymer hydrogels for three-dimensional electrical control of encapsulated living cells

Three-dimensional encapsulation of a living human cervical cancer HeLa cell in a redox-active cytocompatible phospholipid polymer hydrogel and the regulation of cell functions with simple bioelectrical stimulation were investigated. A redox-active and cytocompatible polymer based on the water-soluble phospholipid polymer, poly(2-methacryloyloxyethyl phosphorylcholine (MPC)-co-n-butyl methacrylate (BMA)-co-p-vinylphenylboronic acid (VPBA)-co-vinylferrocene (VFc)) (PMBVF) was synthesized by conventional radical polymerization method. A HeLa-Fucci cell, a human cervical cancer HeLa cell stably expressing fluorescent ubiquitination-based cell cycle indicator (Fucci) were cultured and suspended into the medium, in which a PMBVF polymer were pre-dissolved with desired concentration. Poly(vinyl alcohol) (PVA) solution was added to this PMBVF/HeLa-Fucci medium solution with gently mixing at room temperature, in which case, a reversible PMBVF/PVA hydrogel with encapsulated HeLa-Fucci cells was obtained. The morphologies of the PMBVF/PVA hydrogel and the three-dimensional encapsulated HeLa-Fucci cells were confirmed with microscopy. Cyclic voltammograms results indicated that PMBVF/PVA hydrogel still had excellent electrochemical properties even in the presence of living HeLa-Fucci cells. A constant voltage (0.4 V vs. Ag/AgCl) was applied to the extracellular environment of encapsulated cells as electrical stimulation and the cell cycle progression was calculated base on the analysis of fluorescent images. Compared with that without electrical stimulation, a delay of the cell cycle progression could be observed between 8 h and 18 h while the cells were encapsulated in the hydrogel with electrical stimulation. The investigation of cell functions based on a three-dimensional electrical stimulation with a redox-active cytocompatible phospholipid polymer hydrogel will promote the development of electrochemical therapy of cancer and tumor.

Cross-linkable and water-soluble phospholipid polymer as artificial extracellular matrix

The objective of this study is to prepare an artificial extracellular matrix (ECM) for cell culture by using polymer hydrogels. The polymer used is a cytocompatible water-soluble phospholipid polymer: poly[2-methacryloyloxyethyl phosphorylcholine (MPC)-n-butyl methacrylate-p-nitrophenyloxycarbonyl poly(ethylene oxide) methacrylate (MEONP)] (PMBN). The hydrogels are prepared using a cross-linking reaction between PMBN and diamine compounds, which can easily react to the MEONP moiety under mild conditions. The most favorable diamine is the bis(3-aminopropyl) poly(ethylene oxide) (APEO). The effects of cross-linking density and the chemical structure of cross-linking molecules on the mechanical properties of the hydrogel are evaluated. The storage modulus of the hydrogel is tailored by tuning the PMBN concentration and the MEONP/amino group ratio. The porous structure of the hydrogel networks depends not only on these parameters but also on the reaction temperature. We prepare a hydrogel with 40–50

Encapsulation of <i>shewanella</i> in the redox phospholipid polymer hydrogel for microbial fuel cell fabrication

In this research, encapsulation of Shewanella oneidensis MR-1 in the phospholipid polymer hydrogel and electrochemical property of the hydrogel with immobilized shewanella was investigated. Cytocompatible and electron transfer mediated polymer based on the water-soluble phospholipid polymer, poly(2-methacryloyloxyethyl phosphorylcholine (MPC)-co-n-butyl methacrylate (BMA)-co-p-vinylphenylboronic acid (VPBA)-co-vinylferrocene (VFc)) (PMBVF) was synthesized by conventional radical polymerization method. Shewanella which have the ability to generate and transfer extracellular electron without any external mediator, have significant potential on the fabrication of microbial fuel cell. The water-soluble PMBVF was dissolved in the cell culture medium containing shewanella cells. Poly(vinyl alcohol) (PVA) solution was added to the PMBVF solution with gently mixing, in which case, a reversible PMBVF/PVA hydrogel with encapsulated shewanella was obtained. The viability of the encapsulated shewanella was calculated by the fluorescence microscopy. The electrochemical property of the PMBVF/PVA hydrogel containing shewanella was measured by cyclic voltammograms (CV) and amperometric i-t curve. PMBVF/PVA hydrogel can provide mild environment for the shewanella and maintain the cellular function for longtime. The generated current was higher than that cultured with normal medium.

Regulation of cell proliferation by multi-layered phospholipid polymer hydrogel coatings through controlled release of paclitaxel

We fabricated multi-layered hydrogels on titanium alloy (Ti) surfaces by applying alternating layers of a water-soluble phospholipid polymer (PMBV) and polyvinyl alcohol (PVA). This was accomplished by a layer-by-layer (LbL) process that is based on the formation of reversible covalent bonds between the boronic acid subunits in the PMBV and the hydroxyl groups in the PVA. When placed in an aqueous medium, PMBV acquires a polymeric aggregate structure with hydrophobic domains that can effectively solubilize hydrophobic molecules such as the anticancer drug paclitaxel (PTX) used in this study. The PTX-containing PMBV layer acted as a reservoir in the multi-layered hydrogels. To obtain diverse release profiles, the PTX was loaded in either the top layer (top-type) or the bottom layer (bottom-type) of the hydrogels; additional layers of PMBV and PVA, without PTX, functioned as a diffusion-barrier. In cell culture experiments, top-type hydrogels demonstrated excessive suppression of human epidermal carcinoma A431 cell proliferation over 5 days due to the initial high concentration of released PTX. However, bottom-type hydrogels were able to maintain a constant cell number profile. The release of PTX from multi-layered hydrogels was governed by both diffusion through the diffusion-barrier and dissociation of the hydrogel through an exchange reaction of phenylboronic acid subunits with the low-molecular weight d-glucose in the cell culture medium. In the cell culture experiments, the cell cycle was arrested in S and G2/M phases, as expected following PTX-mediated growth inhibition; control hydrogels did not demonstrate any appreciable cell cycle arrest. We concluded that cell proliferation could be controlled by the concentration of PTX released from the multi-layered hydrogels prepared through the LbL process. This system when used to solubilize bioactive agents at an appropriate layer within the hydrogel has potential for localized and surface-mediated delivery of bioactive molecules from biomedical devices.

Effects of 3,4-dihydrophenyl groups in water-soluble phospholipid polymer on stable surface modification of titanium alloy

The surface of a titanium (Ti) alloy substrate was modified by a simple and quick process using a water-soluble polymer, and the effects of 3,4-dihydroxyphenyl (DHP) groups in the polymer side chain on the modification process were examined. The polymers (PMDP) composed of both 2-methacryloyloxyethyl phosphorylcholine (MPC) unit and 3,4-dihydroxyphenyl methacrylate unit were synthesized for surface anchoring. The Ti alloy substrate was coated with PMDP using an aqueous solution of the polymer. A PMDP layer with a thickness of 20 nm was formed on the Ti alloy substrate simply by dip coating for 10s without drying. Even when the Ti alloy substrate with PMDP coating was immersed in the aqueous medium for 1 week, no change in the thickness was observed, i.e., the PMDP layer was bound to the surface very stably. Oxidation of the DHP groups reduced the stability of the polymer layer significantly. Thus, the DHP groups play a significant role in achieving stable binding. Protein was adsorbed on the Ti alloy substrate; however, this was not observed for the PMDP-coated Ti alloy substrate. In conclusion, we confirmed the effects of DHP groups in PMDP on the stability of the coating on the Ti alloy substrate. Moreover, we found that surface treatment using PMDP was simple, quick, and reliable, and thus, it has great potential for improving biofouling of Ti alloy substrates used in medical devices.

Well-Controlled Cationic Water-Soluble Phospholipid Polymer−DNA Nanocomplexes for Gene Delivery

The facile synthesis of biocompatible and nontoxic gene delivery vectors has been the focus of research in recent years due to the high potential in treating genetic diseases. 2-Methacryloxyethyl phosphorylcholine (MPC) copolymers were recently studied for their ability to produce nontoxic and biocompatible materials. The synthesis of well-defined and water-soluble MPC polymer based cationic vectors for gene delivery purposes was therefore attractive, due to the potential excellent biocompatibility of the resulting copolymers. Herein, cationic MPC copolymers of varying architectures (block versus random) were produced by the reversible addition--fragmentation chain transfer (RAFT) polymerization technique. The copolymers produced were evaluated for their gene delivery efficacy in the presence and absence of serum. It was found that copolymer architectures and molecular weights do affect their gene delivery efficacy. The statistical copolymers produced larger particles, and showed poor gene transfection efficiency as compared to the diblock copolymers. The diblock copolymers served as efficient gene delivery vectors, in both the presence and absence of serum in vitro. To the best of our knowledge, this is the first report where the effect of architecture of MPC based copolymer on gene delivery efficacy has been studied.

Spontaneous Formation of a Hydrogel Composed of Water-Soluble Phospholipid Polymers Grafted with Enantiomeric Oligo(lactic acid) Chains

We designed and synthesized water-soluble biocompatible and biodegradable polymers composed of 2-methacryroyloxyethyl phosphorylcholine and oligo(L- or D-lactic acid) macromonomers to develop an injectable hydrogel matrix. Aqueous solutions containing the polymers with oligo(L-lactic acid) (OLLA) and oligo(D-lactic acid) (ODLA) chains underwent spontaneous gelation when mixed together. This was due to the formation of a stereocomplex between the OLLA and ODLA side-chains, which act as cross-linking components in the hydrogel. Therefore, the hydrogel could be re-dissolved in a buffer solution by hydrolysis of the oligo(lactic acid) chains. We obtained an injectable, biocompatible and degradable hydrogel, and we anticipate that it will be used in applications involving the controlled release of bioactive molecules and cell-based tissue engineering.

Conformational recovery and preservation of protein nature from heat-induced denaturation by water-soluble phospholipid polymer conjugation

The effect of water-soluble phospholipid polymer conjugated to a protein on conformational change during heat-quenched stress was investigated in this study. Well-defined pyridine disulfide end-functional poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) was synthesized by well controlled atom transfer radical polymerization method. Synthesized PMPC was the site specifically conjugated to a protein, and the effect on conformational change during heat-quenched stress was estimated by circular dichroism and fluorescence study. As a result, a single phospholipid polymer chain conjugated to a protein give a great effect on conformational preservation in both secondary and tertiary structures even after the heat-quenced process. Moreover, even the conformational recovery which gave the completely reversible conformational preservation was observed in circular dichroism study. The resulting protein activity was also confirmed, and no significant decline was induced by heat-quenched stress.

Smart controlled preparation of multilayered hydrogel for releasing bioactive molecules

We focused on layer-by-layer (LBL) method which has emerged as a versatile and efficient technique. The preparation of multilayered hydrogel can resolve the problems. We fabricated and characterized pH-controlled preparation of polymer multilayer via LbL method on titanium alloy surface for releasing the growth factor. To achieve this purpose, we synthesized water-soluble phospholipid polymer (PMDV) having both N, N-dimethylaminoethyl methacrylate (DMAEMA) as pH-sensitive unit and 4-vinylphenylboronic acid (VPBA) moiety as sugar binding units. To construct the multilayered hydrogel, alginate (ALG), which possesses a polysaccharide comprised of two repeating carboxylated monosaccharide units was used. We could construct multilayered hydrogel easily by using two interaction types. The first is the electrostatic interaction between positively charged DMAEMA and negatively charged carboxyl group of ALG, and the second is the covalent bonding between VPBA and diol of ALG. Multilayered PMDV and ALG hydrogel was characterized by contact angle measurement, surface plasmon resonance. The results demonstrate that the surface composition of the multilayered hydrogel can be simply constructed via LbL process and VEGF release can be released during 1 week. We expect this system will be applied in biomedical and drug delivery system.

Biodegradable polymer films for releasing nanovehicles containing sirolimus

To obtain novel biodegradable sirolimus-releasing polymer films that could release nanovehicles incorporating sirolimus, polyester, a water-soluble amphiphilic phospholipid polymer, and sirolimus were blended. The sirolimus-releasing polymer films were characterized by scanning electron microscopy and differential scanning calorimetry. Nanovehicles were formed with the phospholipid polymer chains and could be released from the sirolimus-releasing polymer films. The hydrodynamic diameter of the nanovehicles in phosphate-buffered saline was smaller than 20 nm. The nanovehicles substantially enhanced the carrier-mediated delivery of sirolimus and attenuated its degradation product. This study demonstrates that the delivery of sirolimus was enhanced by nanovehicles released from sirolimus-eluting materials.

Surface immobilization of biocompatible phospholipid polymer multilayered hydrogel on titanium alloy

The aim of this study is to improve the biocompatibility of titanium alloy (Ti) implants by immobilization of multilayered phospholipid polymer hydrogel able to reduce protein adsorption and cell adhesion. We fabricated and characterized a multilayered hydrogel on Ti substrate via a layer-by-layer self-assembly deposition method using a phospholipid polymer bearing a phenylboronic acid moiety and poly(vinyl alcohol) (PVA). The water-soluble phospholipid polymer (PMBV) was synthesized from 2-methacrylocyloxyethyl phosphorylcholine, n-butyl methacrylate, and 4-vinylphenylboronic acid (VPBA). The PMBV reacted with PVA and formed a hydrogel due to covalent linkage between the VPBA units and hydroxyl groups of PVA. The hydrogel layer growth on the Ti surface was initialized by the deposition of one layer of photoreactive PVA bonded by UV irradiation to the Ti surface, which was modified with an alkylsilane compound. The multilayered hydrogel was built up by alternating the deposition of the PMBV and PVA; this was monitored by several methods: static contact angle measurement, X-ray photoelectron spectroscopy, and attenuated Fourier-transform infrared spectroscopy. The results revealed clearly the progressive construction of the multilayered hydrogel on the Ti substrate. The PMBV/PVA multilayer prepared on the Ti substrate reduced the adhesion of L929 cells compared with that on an untreated Ti substrate. Thus, we concluded that the formation of the multilayered hydrogel is effective to improve the biocompatibility on Ti-based medical devices.

Temporal and spatially controllable cell encapsulation using a water-soluble phospholipid polymer with phenylboronic acid moiety

Temporal and spatially controllable cell encapsulation based on a water-soluble phospholipid polymer is reported in this study. Phospholipid polymers, i.e., poly(2-methacryloyloxyethyl phosphorylcholine- co- n-butyl methacrylate- co- p-vinylphenylboronic acid) (PMBV), were synthesized. A series of hydrogels was prepared between the water-soluble PMBV and other water-soluble polymers having multi-valent alcoholic groups, such as poly(vinyl alcohol) (PVA). The PMBV/PVA hydrogels were formed not only in water, but also in a cell culture medium, and dissociated by the excess addition of low molecular weight di-valent hydroxyl compounds, such as d-glucose. The PMBV/PVA hydrogel was applied as a cell-container which has three-dimensional matrices for the reversible encapsulation of living cells without any response in it. Uniform cell seeding can be achieved using the hydrogels due to the homogenous gel formation of PMBV and PVA in the cell culture medium. Fibroblast cells were encapsulated in the PMBV/PVA hydrogel and maintained for 1 week. After dissociation of the PMBV/PVA hydrogel, the cells were seeded on conventional tissue culture polystyrene. The cells adhered and proliferated as usual on the plate. That is, the PMBV/PVA hydrogel will be useful as a cell-container, which can maintain the cells without any significant adverse effect on the entrapped cells.