• Biomaterials and Biomechanics in Bioengineering
• /
• v.1 no.1
• /
• pp.1-12
• /
• 2014

Polymer multilayered hydrogels were prepared on a titanium alloy (Ti) substrate using a layer-by-layer (LBL) process to load a cell growth factor. Two water-soluble polymers were used to fabricate the multilayered hydrogels, a phospholipid polymer with both N, N-dimethylaminoethyl methacrylate (DMAEMA) units and 4-vinylphenylboronic acid (VPBA) units [poly(MPC-co-DMAEMA-co-VPBA) (PMDV)], and the polysaccharide alginate (ALG). PMDV interacted with ALG through a selective reaction between the VPBA units in PMDV and the hydroxyl groups in ALG and through electrostatic interactions between the DMAEMA units in PMDA and the anionic carboxyl groups in ALG. First, the Ti substrate was covered with photoreactive poly vinyl alcohol, and then the Ti alloy was alternately immersed in the respective polymer solutions to form the PMDV/ALG multilayered hydrogels. In this multilayered hydrogel, vascular endothelial growth factor (VEGF) was introduced in different layers during the LbL process under mild conditions. Release of VEGF from the multilayered hydrogels was dependent on the location; however, release continued for 2 weeks. Endothelial cells adhered to the hydrogel and proliferated, and these corresponded to the VEGF release profile from the hydrogel. We concluded that multilayered hydrogels composed of PMDV and ALG could be loaded with cell growth factors that have high activity and can control cell functions. Therefore, this system provides a cell function controllable substrate based on the controlled release of biologically active proteins.

• Biomaterials and Biomechanics in Bioengineering
• /
• v.1 no.3
• /
• pp.163-174
• /
• 2014

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 $40-50{\mu}m$ diameter pores and more than 90 wt% swelling. The permeation of proteins through the hydrogel increases dramatically with an increase in pore size. To induce cell adhesion, the cell-attaching oligopeptide, RGDS, is immobilized onto the hydrogel using MEONP residue. Bovine pulmonary artery endothelial cells (BPAECs) are cultured on the hydrogel matrix and are able to migrate into the artificial matrix. Hence, the RGDS-modified PMBN hydrogel matrix with cross-linked APEO functions as an artificial ECM for growing cells for applications in tissue engineering.

• Macromolecular Research
• /
• v.11 no.2
• /
• pp.115-121
• /
• 2003

In this research, the in vitro anti-thrombogenecity of artificial materials was evaluated using hydrophilic/hydrophobic copolymers containing oiligosaccharide as hydrophilic moiety and phospholipid as hydrophobic moiety respectively. N-(p-vinylbenzyl)-[O-$\alpha$-D-glucopyranosyl-(1longrightarrow4)]$_{n-1}$-D-glucoamide(VM7A) was (VM7 A) was adopted as hydrophilic oligosaccharide and 2-acryloxybutyl-2-(triethylammonium)ethyl phosphoric acid (HBA-choline) was adopted as hydrophobic phospholipid. Copolymers having various monomer feeding molar ratios were synthesized through radical polymerization. The synthesized copolymers were identified using FT-IR, $^1$H-NMR, XPS, and DSC. The surface energy of the copolymers were evaluated by dynamic contact angle (DCA) method and checked different roles of VM7A as hydrophilic moiety and HBA-choline as hydrophobic moiety on surface. The surface morphological differences between hydrated and unhydrated surfaces of copolymers were observed and evaluated using Am. The platelets were separated from canine whole blood by centrifugation and adopted to the anti-thromobogenecity test of the copolymers. From the results, we find out that as VM7A ratio increases, so did anti-thrombogenecity. Such results show the possibility of using these copolymers as blood compatible materials in living body.y.

• Biomaterials and Biomechanics in Bioengineering
• /
• v.1 no.2
• /
• pp.95-104
• /
• 2014

The objective of this study was to evaluate the cytotoxicity of poly (lactic acid) (PLA) nanoparticles. We used a water-soluble, amphiphilic phospholipid polymer, poly (2-methacryloyloxyethyl phosphorylcholine-co-n-butyl methacrylate) (PMB30W), as a stabilizer for the PLA nanoparticles. The PLA nanoparticles and PMB30W-modified PLA (PLA/PMB30W) nanoparticles were prepared by evaporating tetrahydrofuran (THF) from its aqueous solution. Precipitation of the polymers from the aqueous solution produced PLA and PLA/PMB30W nanoparticles with a size distribution of $0.4-0.5{\mu}m$. The partial coverage of PMB30W on the surface of the PLA/PMB30W nanoparticles was confirmed by X-ray photoelectron spectroscopy (XPS) and dynamic light-scattering (DLS). A high-content automated screening assay (240 random fields per group) revealed that the PLA nanoparticles induced apoptosis in a mouse macrophage-like cell line (apoptotic population: 73.9% in 0.8 mg PLA/mL), while the PLA/PMB30W nanoparticles remained relatively non-hazardous in vitro (apoptotic population: 13.8% in 0.8 mg PLA/mL). The reduction of the apoptotic population was attributed to the phosphorylcholine groups in the PMB30W bound to the surface of the nanoparticle. In conclusion, precipitation of PLA in THF aqueous solution enabled the preparation of PLA nanoparticles with similar shapes and size distribution but different surface characteristics. PMB30W was an effective stabilizer and surface modifier, which reduced the cytotoxicity of PLA nanoparticles by enabling their avoidance of the mononuclear phagocyte system.

• Journal of Microbiology and Biotechnology
• /
• v.12 no.6
• /
• pp.957-961
• /
• 2002

The hypolipidemic effect of exe-polymer produced in submerged mycelial culture of Hericium erinaceus (HE), Auricularia auricula-judue (AA), Flammulina veluripes (FV), Phellinus pini (PP), and Grifola frondosa (GF) was investigated in dietary-induced hyperlipidemic rats. The animals were administered with exe-polymers at the level of 100 mg/kg body weight daily for four weeks. Hypolipidemic effect was achieved in all the experimental groups, however, HE exo-polymer proved to be the most potent one, which significantly reduced the plasma triglyceride ($28.9\%$), total cholesterol ($29.7\%$), low-density lipoprotein (LDL) cholesterol ($39.6\%$), phospholipid ($16.0\%$), and liver total cholesterol ($28.9\%$) level, when compared to the saline administered (control) group. The results of the present investigation strongly demonstrate the potential of HE exe-polymer in combating hyperlipidemia in the experimental animals.

• Archives of Pharmacal Research
• /
• v.27 no.11
• /
• pp.1177-1182
• /
• 2004

The effect of poly[2-methacryloyloxyethyl phosphorylcholine] (pMPC) on the skin permeation property was investigated by performing in vitro skin permeation study of a model drug, nicotinic acid (NA). Effect of pMPC polymer in donor solution on skin permeation rates was evaluated using side-by-side diffusion cells. Also, the structural alterations in the stratum corneum (SC), inter-lamellar bilayer (ILB) and dermis layers in pMPC-treated and -untreated skin sections were investigated with transmission electron microscopy (TEM). The permeation profile of NA without pMPC in donor solution showed biphasic mode: initial $1^{st} phase and 2^{nd}$ hydration phase. The sudden, more than 10-fold increase in flux from the initial steady state (43.5 $\mu g/cm^2$/hr) to the $2^{nd}$ hydration phase (457.3 $\mu g/cm^2$/hr) suggests the disruption of skin barrier function due to extensive hydration. The permeation profile of NA with 3% pMPC in the donor solution showed monophasic pattern: the steady state flux (10.9 $\mu g/cm^2$/hr) without abrupt increase of the flux. The degree of NA permeation rate decreased in a concentration-dependent manner of pMPC. TEM of skin equilibrated with water or 2% pMPC for 12 h showed that corneocytes are still cohesive and epidermis is tightly bound to dermis in 2% pMPC-treated skin, while wider separation between corneocytes and focal dilations in inter-cellular spaces were observed in water-treated skin. This result suggests that pMPC could protect the barrier property of the stratum corneum by preventing the disruption of ILB structure caused by extensive skin hydration during skin permeation study.

• Biomaterials and Biomechanics in Bioengineering
• /
• v.3 no.1
• /
• pp.37-46
• /
• 2016

To maintain activity in a coenzyme/enzyme mixture system, such as ${\beta}$-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 $37^{\circ}C$ 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 ($MSO_3$)] ($PMMSO_3$). The poly($MSO_3$) was used as a reference. For the PMQ and $PMSO_3$ 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($MPC-co-MSO_3$) ($PMMSO_3$) 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 $PMMSO_3$ compared with that in the $PMSO_3$ solution. The mixture of two polymers, poly(MPC) and poly($MSO_3$), did not produce any stabilization. Thus, both the MPC and $MSO_3$ units in the polymer chain had important and cooperative effects for stabilizing the NADH/LDH mixture.

• Proceedings of the Membrane Society of Korea Conference
• /
• 1992.10a
• /
• pp.47-48
• /
• 1992

Polymer containing monomers with pendant phospholipid polar group, 2-(metha-cryloyoxy) ethyl-2-(trimethylammonium) ethyl phosphate(MTP) were synthesized and blood compatibility of the copolymers was evaluated. Good permeability of biocomponents of molecular weight below 10$^4$ through cellulosic membrane coated with the copolymer of 2-(methacryloyoxy) ethyl-2-(tri-methylammonium)ethyl phosphate, butylmethacrylate(BMA), and glycidyl methacrylate(GMA) was observed, (Fig.1).

• Macromolecular Research
• /
• v.16 no.7
• /
• pp.596-603
• /
• 2008

To improve the mechanical properties, dimensional stability and blood compatibility, the biomedical material $Pellethene^{(R)}$ was blended with multiblock polyurethane (MPU) containing phospopholipid/long alkyl chain (C-18) at the various MPU contents and crosslinked using dicumyl peroxide as a crosslinking agent. The maximum MPU content for stable $Pellethene^{(R)}$/MPU blended films was approximately 30 wt%. The optimum crosslinking agent content and crosslinking time with respect to the mechanical properties were 4 wt% and 3 h, respectively. The mechanical properties (tensile strength and elongation at break) and water absorption of the crosslinked blend film increased with increasing MPU content. The test of platelet adhesion on the surfaces of the crosslinked blend film showed a decrease in the level of platelet adhesion from 70% to 6% with increasing MPU content from 0 to 30 wt%. These results suggest that the crosslinked $Pellethene^{(R)}$/MPU-30 (MPU content: 30 wt%) sample has strong potential as a novel material for blood compatible material applications.

• Macromolecular Research
• /
• v.9 no.2
• /
• pp.107-115
• /
• 2001

Poly(L-lactide-co-glycolide)(PLGA) was blended with poly[$\omega$-methacryloyloxyethyl phospho-rylcholine-co-ethylhexylmethacrylate (PMEH)] (PLGA/PMEH) to endow with new functionality i.e., to improve the cell-, tissue- and blood-compatibility. The characteristics of surface properties were investigated by measurement of contact angle goniometer, Fourier-transform infrared spectroscopy with attenuated total reflectance (FTIR-ATR) and electron spectroscopy for chemical analysis (ESCA). NIH/3T3 fibroblast and bovine aortic endothelial cell were cultured on control and PLGA/PMEH surfaces for the evaluation of ceil attachment and proliferation in terms of surface functionality such as the concentration of phosphoryl-choline. Also, the behavior of platelet adhesion on PLGA/PMEH was observed in terms of the surface functionality. The contact angles on control and PLGA/PMEH surfaces decreased with increasing PMEH content from 75$^{\circ}$ to about 43$^{\circ}$. It was observed from the FTIR-ATR spectra that phosphorylcholine groups are gradually increased with increasing blended amount of MPC. The experimental P percent values from ESCA analysis were more 3.28∼7.4 times than that of the theoretical P percent for each blend films. These results clearly indicated that the MPC units were concentrated on the surface of PLGA/PMEH blend. The control and PLGA/PMEH films with 0.5 to 10.0 wt% concentration of PMEH were used to evaluate cell adhesion and growth in terms of phosphorylcholine functionality and wettability. Cell adhesion and growth on PLGA/PMEH surfaces were less active than those of control and both cell number decreased with increasing PMEH contents without the effect of surface wettability. It can be explained that the fibronectin adsorption decreased with an increase in the surface density of phosphorylcholine functional group. One can conclude the amount of the protein adsorption and the adhesion number of cells can be controlled and nonspecifically reduced by the introduction with phosphorylcholine group. Morphology of the adhered platelets on the PLGA/PMEH surface showed lower activating than control and the number of adhered platelets on the PLGA/PMEH sample decreased with increasing the phosphorylcholine contents. The amount of fibrinogen adsorbed on the PLGA/PMEH surface demonstrated that the phospholipid polar group played an important role in reducing protein adsorption on the surface. In conclusion, this surface modification technique might be effectively used PLGA film and scaffolds for controlling the adhesion and growth of cell and tissue, furthermore, blood compatibility of the PLGA was improved by blending of the MPC polymer for the application of tissue engineering fields.