Grafting reactions onto poly(organophosphazenes), 7. Light-induced grafting of poly(vinyl acetate) onto catena-poly[bis(4-methyl-, 4-ethyl- and 4-sec-butylphenoxy)-λ5-phosphazene] and successive hydrolysis to phosphazenegrafted poly(vinyl alcohol)

In this paper we describe the light-induced grafting reaction of poly(vinyl acetate) onto catena-poly[bis(4-sec-butylphenoxy)-λ⁵-phosphazene], catena-poly[bis(4-ethylphenoxy)-λ⁵-phosphazene] and catena-poly[bis(4-methylphenoxy)-λ⁵-phosphazene], and the successive acid- (and base-) catalyzed hydrolysis of the grafted macromolecule to poly-(vinyl alcohol). The process was found to be dependent on the irradiation time, reaction temperature, relative monomer/methanol concentration in the reaction mixture, type of substituents present on the exploited phosphazene polymers, and on the crystallinity of these macromolecules. The new phosphazene grafted copolymers thus prepared have been characterized by IR spectroscopy, gravimetric analysis and contact angle measurements.     

Dielectric properties of poly(dibenzyloxyphosphazene)s

Poly(dibenzyloxyphosphazene) (PBP), poly[bis(4-methylbenzyloxy)phosphazene] (PMBP) and poly[bis(4-chlorobenzyloxy)phosphazene] (PCIBP) were synthesized by reaction of poly(dichlorophosphazene) (PDCIP) and the corresponding sodium benzyl alkoxide. PDCIP was prepared by a ring-cleavage polymerization from hexachlorocyclotriphosphazene. The dielectric properties of the polymers were studied in the temperature range of 80 to 390 K at several frequencies between 0,1 and 100 kHz. Two relaxations, a relaxation above the glass transition temperature T_g and β relaxation below T_g, were observed in PBP and PMBP. The β relaxation was only observed in PCIBP. The a relaxations are related to a glass-rubber transition and the β relaxations to the local molecular motion of the short segments.     

In vitro culture of rat neuromicrovascular endothelial cells on polymeric scaffolds

Polyphosphazenes are polymers possessing a skeleton composed of alternating phosphorous and nitrogen atoms, and two side-moieties linked to each phosphorous atom. Polyphosphazenes with amino acid esters as side-moieties are biocompatible and biodegradable polymers. Two polyphosphazenes, poly[bis(ethyl alanate) phosphazene] and poly[(ethyl phenylalanate)0.8(ethyl alanate)0.8(ethyl glycinate)0.4 phosphazene] (PPAGP) were synthesized, and processed to form small fibers. Their ability to support rat neuromicrovascular endothelial cell (EC) adhesion and growth has been studied, using poly(D,L-lactic acid) as reference compound. Scanning electron microscopy revealed that both poly[bis(ethyl alanate) phosphazene] and PPAGP fibers were thinner than poly(D,L-lactic acid) fibers, and possessed a more irregular and porous surface. All polymers increased EC adhesion, compared with polystyrene, but only polyphosphazenes were able to improve EC growth. The highest increase in EC proliferation was induced by PPAGP, which, as revealed by environmental scanning electron microscopy, was also able to induce ECs to arrange into tubular structures. The conclusion is drawn that PPAGP may provide the best scaffold for engineered blood vessels, because it promotes adhesion, growth, and organization of ECs into capillary-like structures.     

Morphological and structural properties of poly[bis(p-phenylphenoxy)phosphazene]

Poly[bis(p-phenylphenoxy)phosphazene] (PB(4-Ph)PP) has been investigated employing X-ray diffraction technique and electron microscopy. Its unit cell dimensions were determined to be a = 4,18 nm, b = 1,83 nm and c = 0,957 nm with space group Pca2₁. At 21 5–220°C , PB(4-Ph)PP transforms into an anisotropic liquid-like phase corresponding to a new molecular ordering array. The thicker films are composed of the linked globules approximately 100 nm in diameter. Upon drawing, the globules transform into a rod-like morphology 15–40 nm in width and exhibit a highly oriented X-ray diffraction pattern. These unusual morphological features have been compared with features found in poly[bis(phenoxy)phosphazene] and poly[bis(halophenoxy)phosphazene] polymers. X-ray diffraction and crystallization results support a smectic-like side chain morphology.     

Dielectric properties of poly[bis(trifluoroethoxy)phosphazene] and poly[bis(m-methylphenoxy)phosphazene]

Dielectric properties of poly[bis(trifluoroethoxy)phosphazene] (PFEP) and poly[bis(m-methylphenoxy)phosphazene] (PmMPP) were studied in a temperature range from ?195 to 120°C and at several frequencies between 0,1 and 100 kHz. In PFEP, two relaxations, an α relaxation above the glass transition temperature (T_g) and a β relaxation below T_g, which are related to a glass-rubber transition and a local molecular motion of short segments, respectively, were observed. However, PmMPP shows no β relaxation. From the above dielectric results, it was concluded that side groups play an important role in molecular motion of the polyphosphazenes. In PmMPP a γ′ relaxation was found below T_g by immersing the polymers into water. The γ′ relaxation is related to the molecular motin of absorbed water.     

Mechanical properties and osteocompatibility of novel biodegradable alanine based polyphosphazenes: Side group effects

The versatility of polymers for tissue regeneration lies in the feasibility to modulate the physical and biological properties by varying the side groups grafted to the polymers. Biodegradable polyphosphazenes are high-molecular-weight polymers with alternating nitrogen and phosphorus atoms in the backbone. This study is the first of its kind to systematically investigate the effect of side group structure on the compressive strength of novel biodegradable polyphosphazene based polymers as potential materials for tissue regeneration. The alanine polyphosphazene based polymers, poly(bis(ethyl alanato) phosphazene) (PNEA), poly((50% ethyl alanato) (50% methyl phenoxy) phosphazene) (PNEA₅₀mPh₅₀), poly((50% ethyl alanato) (50% phenyl phenoxy) phosphazene) (PNEA₅₀PhPh₅₀) were investigated to demonstrate their mechanical properties and osteocompatibility. Results of mechanical testing studies demonstrated that the nature and the ratio of the pendent groups attached to the polymer backbone play a significant role in determining the mechanical properties of the resulting polymer. The compressive strength of PNEA₅₀PhPh₅₀ was significantly higher than poly(lactide-co-glycolide) (85:15 PLAGA) (p < 0.05). Additional studies evaluated the cellular response and gene expression of primary rat osteoblast cells on PNEA, PNEA₅₀mPh₅₀ and PNEA₅₀PhPh₅₀ films as candidates for bone tissue engineering applications. Results of the in vitro osteocompatibility evaluation demonstrated that cells adhere, proliferate, and maintain their phenotype when seeded directly on the surface of PNEA, PNEA₅₀mPh₅₀, and PNEA₅₀PhPh₅₀. Moreover, cells on the surface of the polymers expressed type I collagen, alkaline phosphatase, osteocalcin, osteopontin, and bone sialoprotein, which are characteristic genes for osteoblast maturation, differentiation, and mineralization.     

Ion-conducting grafted polypropylene film, 2. Volume grafting of polypropylene and gradient composition of poly(propylene-g-acrylic acid)

Grafting of acrylic acid onto a pre-activated polypropylene film was investigated, varying the concentrations of monomer and Fe²⁺ -ions, the polymerization time and temperature. Experiments were planned according to a scheme of a latin square, and statistical analyses were performed for the optimization of the grafting variables. The concentration of ferrous ions was found to be the most significant variable for the graft level. At low concentration, ferrous ions act as activator of grafting but no grafting takes place at relatively high concentrations. The distribution of grafted poly(acrylic acid) within a PP film was examined by microphotometry of the coloured slides of the film. The grafted layer of PP reaches the center only at about 30% of grafted poly(acrylic acid) and up to 70% the distribution of grafted poly(acrylic acid) is still non-uniform with a decreasing amount of the polyacid from the surface to the center. The film samples containing 30% of grafted poly(acrylic acid) already show conductivity in alkaline media and are interesting ion conducting materials.     

Effect of Grafted PP on the Properties of Thermoplastic Elastomers Based on PP‐EPDM Blends

The functionalization of isotactic poly(propylene) (iPP) through grafting with two itaconic acid derivatives, monomethyl and dimethyl itaconate (MMI and DMI, respectively), was performed in the melt using a Brabender plasticorder. The grafting reaction was carried out at 190°C using two different initial monomer concentrations and 2,5‐dimethyl‐2,5‐bis(tert‐butylperoxy)hexane as radical initiator. Two samples of PP grafted with different amounts of either DMI or MMI (0.5 and 1.4 wt.‐%) were used in this work. In order to evaluate the characteristics of these materials, different thermoplastic elastomers based on poly(propylene) and ethylene‐propylene diene rubber blends (50/50) were processed and their properties were analyzed. A comparative study of materials prepared with unmodified PP is also reported. The flow properties analyzed by torque values, melt index and rheological studies showed that the blends prepared with modified PP have a better processability, showing a lower viscosity, with this effect being more significant DMI‐modified PP. Dynamic mechanical analysis and tensile properties revealed that the grafting reaction promotes the interaction between both polymeric phases, giving rise to a more rigid structure. Furthermore, it was observed that the functional polar monomers not only act as compatibilizers but also behave as nucleating agents for PP crystallization, showing a substantial decrease of the half‐time of crystallization, which could be attributed to the presence of a greater number of nuclei during the crystallization process. These results are in agreement with observations carried out by scanning electron microscopy (SEM), where a better interaction between both polymeric phases is observed when PP is functionalized with both itaconic acid derivatives.     

Grafting of proteins onto polymer surfaces with the use of oxidized starch.

A study has been carried out on the coupling of proteins onto crosslinked poly(vinyl alcohol) hydrogel membranes and ethylene-vinyl alcohol copolymer(EVA) films previously grafted with oxidized starches having many pendant aldehyde groups. The coupling reaction of proteins is based on the Schiff's base formation between the amino groups of proteins and the aldehyde groups of the oxidized starches which have been grafted onto the substrate membrane or film through acetalization of the aldehyde of starch with hydroxyl groups of the substrate polymers. The grafting of oxidized starches onto the EVA films seems to be restricted to the film surface, since no detectable change is observed in the weight and the attenuated total reflection infrared spectrum of the grafted films. The amount of grafted protein, determined by the ninhydrin method, reveals that, at least, plasma proteins such as serum albumin and fibrinogen are grafted to the film surface in a monomolecular layer without undergoing a marked denaturation. The alpha-amylase grafted onto the EVA film showed a distinct enzymatic activity in hydrolysis of amylose and starch, but the activity was very low compared with that of the ungrafted, soluble alpha-amylase.     

Interactions of poly(ethylene glycol)-grafted cellulose membranes with proteins and platelets.

The interactions of proteins and platelets with cellulose membranes grafted with poly(ethylene glycol) were studied. The poly(ethylene glycol) grafting was carried out using poly(ethylene glycol)-monoacid and poly(ethylene glycol)-diacid, which have one and two terminal carboxyl groups, respectively. The grafting operates through esterification between the carboxyl groups of poly(ethylene glycol) and the hydroxyl groups on the membrane surface. Both of the poly(ethylene glycol) grafted membranes reduced the complement activation. Adsorption of bovine serum albumin and gamma-globulin increased when the membrane was grafted with poly(ethylene glycol)-diacid, but did not change when it was grafted with poly(ethylene glycol)-monoacid. When platelets were incubated with serum proteins, the platelet adhesion to the membranes slightly decreased by grafting both the poly(ethylene glycol)-diacid and poly(ethylene glycol)-monoacid. The poly(ethylene glycol)-diacid grafted surface showed more clotting than the poly(ethylene glycol)-monoacid grafted and original surfaces.     

Tailor-made functional surfaces: potential elastomeric biomaterials I

In the present investigation, different functional monomers, like hydroxyethyl methacrylate, acrylic acid, N-vinyl pyrrolidone and glycidyl methacrylate, have been grafted onto the surface of EPDM film (approx. 200 microm) using simultaneous photo-grafting (lambda > or = 290 nm) and cold plasma-grafting techniques, to alter the surface properties, such as hydrophilicity and, therefore, biocompatibility. Here, we have carried out simultaneous plasma-grafting, unlike the conventional post plasma-grafting. The effect of different surface grafting techniques on the degree of surface modification and resultant biocompatibility has been investigated. The chemical changes on the polymer backbone are followed from the results of attenuated total reflection Fourier transform infrared (ATR-FT-IR) spectroscopy and X-ray photoelectron spectroscopy (XPS), which shows the peaks corresponding to the functional groups of the monomers grafted onto the film surface. The morphology of the modified surfaces was investigated using scanning electron microscopy (SEM) technique. The induced hydrophilicity and resultant cell compatibility were followed from the water contact angle measurements and in vitro human carcinoma cell adhesion/proliferation tests, respectively. All the grafted samples exhibited variable cell compatibilities depending upon the type of monomer and their degree of grafting; however, always better than the neat samples. Hydroxyethyl methacrylate and acrylic acid showed exceptionally high cell compatibility in terms of cell adhesion and proliferation.     

Protein-Resistant Materials via Surface-Initiated Atom Transfer Radical Polymerization of 2-Methacryloyloxyethyl Phosphorylcholine

Poly(2-methacryloyloxyethyl phosphorylcholine) (poly(MPC)) was grafted from various polymeric substrates to prepare protein-resistant materials. The poly(MPC) chain length was adjusted via the ratio of monomer to sacrificial initiator in solution. The surfaces were characterized by water contact angle and X-ray photoelectron spectroscopy (XPS). The protein-resistant properties of the poly(MPC)-grafted surfaces were evaluated by single adsorption experiments with fibrinogen and lysozyme. It was shown that the simple three-step grafting method could be applied to modify various biomaterial surfaces including polyurethane and silicones. The adsorption of fibrinogen and lysozyme to the modified surfaces was greatly reduced compared to the unmodified surfaces, and adsorption decreased with increasing poly(MPC) chain length. On polyurethane film grafted with poly(MPC) of chain length 100, the reduction in adsorption was approx. 96% for lysozyme and approx. 99% for fibrinogen.     

Tailor-made functional surfaces: potential elastomeric biomaterials I

In the present investigation, different functional monomers, like hydroxyethyl methacrylate, acrylic acid, N-vinyl pyrrolidone and glycidyl methacrylate, have been grafted onto the surface of EPDM film (approx. 200 μm) using simultaneous photo-grafting (λ ≥ 290 nm) and cold plasma-grafting techniques, to alter the surface properties, such as hydrophilicity and, therefore, biocompatibility. Here, we have carried out simultaneous plasma-grafting, unlike the conventional post plasma-grafting. The effect of different surface grafting techniques on the degree of surface modification and resultant biocompatibility has been investigated. The chemical changes on the polymer backbone are followed from the results of attenuated total reflection Fourier transform infrared (ATR-FT-IR) spectroscopy and X-ray photoelectron spectroscopy (XPS), which shows the peaks corresponding to the functional groups of the monomers grafted onto the film surface. The morphology of the modified surfaces was investigated using scanning electron microscopy (SEM) technique. The induced hydrophilicity and resultant cell compatibility were followed from the water contact angle measurements and in vitro human carcinoma cell adhesion/proliferation tests, respectively. All the grafted samples exhibited variable cell compatibilities depending upon the type of monomer and their degree of grafting; however, always better than the neat samples. Hydroxyethyl methacrylate and acrylic acid showed exceptionally high cell compatibility in terms of cell adhesion and proliferation.     

Grafting copolymerization of 2-methacryloyloxyethyl phosphorylcholine (MPC) onto pre-irradiated cellulose films

Grafting of 2-methacryloyloxyethyl phosphorylcholine (MPC) and poly(ethylene glycol mathacrylate) (PEGMA) onto cellulose films was performed using the pre-irradiation grafting method. The effects of monomer concentration, solvent system and co-solvent composition, and reaction time on the degree of grafting were determined. The grafted samples were confirmed by FT-IR-ATR spectra. The blood compatibilities of the grafted cellulose were evaluated by platelet-rich plasma contact studies and viewed by scanning electron microscopy; non-grafted cellulose film sample was used as references. As a result, MPC and MPC/PEGMA were grafted on the surface of cellulose films. It was found that fewer platelets adhered to the MPC-grafted surfaces and that they showed less shape variation than the ungrafted references.     

Platelet adhesive resistance of segmented polyurethane film surface-grafted with vinyl benzyl sulfo monomer of ammonium zwitterions

Platelet from human plasma adhered on the segmented poly(ether urethane) (SPEU) film grafted with N,N-dimethyl-N-(p-vinylbenyl)-N-(3-sulfopropyl) ammonium (DMVSA) was studied. SPEU films were hydroxylated by potassium peroxosulfate (KPS) and then grafted with DMVSA using ceric ammonium nitrate (CAN) as initiator. The mixing time of hydroxylated SPEU/CAN and the monomer concentration effect on graft polymerization yield were determined by ATR-FTIR. Surface analysis of the grafted films by ATR-FTIR and ESCA confirmed that DMVSA was successfully grafted onto the SPEU film surface. The grafted film possessed a relatively hydrophilic surface, as revealed by water contact angle measurement. The improved blood compatibility of the grafted films was preliminarily evaluated by a platelet-rich plasma adhesion study and scanning electron microscopy, using original SPEU and hydroxylated SPEU films as the controls. The results showed that platelet attachment was decreased greatly on the segmented polyurethane films grafted with DMVSA. This kind of new biomaterials grafted with sulfo ammonium zwitterionic monomers might have potential for biomedical applications.     

温敏型智能化靶向式药物载体研究（I）——具有温敏开关的多孔膜

研究了膜孔内接枝聚异丙基丙烯酰胺 (PNIPAM)“开关”的温敏型智能膜的制备 ,并对其进行了温度感应开关性能实验。实验中采用等离子体接枝填孔聚合法将 PNIPAM接枝在多孔平板膜的膜孔中 ,结果表明 ,这种接枝了 PNIPAM“开关”的多孔膜具有温度感应特性 ,其利用膜孔内 PNIPAM接枝链的膨胀 -收缩特性实现了感温性开关性能。当环境温度低于 PNIPAM的低临界溶解温度 (L CST)时 ,膜孔内 PNIPAM分子链膨胀而使膜孔呈“关闭”状态 ;而当环境温度高于 L CST时 ,PNIPAM分子链变为收缩状态而使膜孔“开启”。温敏开关的 L CST可通过添加丙烯酰胺 (AAM)与异丙基丙烯酰胺 (NIPAM)共聚来调节 ,AAM与 NIPAM共聚开关的 L CST随 AAM添加量的增加而单调上升。     

Chemical structure of vinyl alcohol/acrylamide graft copolymers prepared by the cerium(IV) ion method

Graft copolymerization of acrylamide onto poly(vinyl alcohol) (PVA) samples with different 1,2-diol content was carried out by the Ce(IV) ion method. The poly(acrylamide) (PAAd) side chains were separated by oxidative degradation of the PVA backbone with nitric acid at which treatment the PAAd side chains reacted to poly(acrylic acid) (PAA) chains without a change of the degree of polymerization. The chemical structure of the graft copolymers was clarified on the basis of the number average molecular weights of the pure graft copolymer, of separated branches, and of the mother PVA molecules and the chemical composition of the graft copolymers. It was found that the number of branches per molecule was greater than one and increased with increasing content of 1,2-diol structures in the PVA mother molecule. A number of grafted branches as high as 12 caused the graft copolymer to be insoluble in water.     

Study of the structure of polyethylene and poly(tetrafluoroethylene) radiation grafted ion-exchange copolymers

Cation- and anion-exchange copolymers were synthesized by radiation induced copolymerization of acrylic acid and 4-vinylpyridine onto polyethylene and poly(tetrafluoroethylene) (PTFE) films. The grafting was carried out by the direct method of single or multiple (discrete) irradiation by γ-rays from a ⁶⁰Co source. The grafting degree was from 10 to 121% for polyethylene and from 2.5 to 50% for poly(tetrafluoroethylene), depending on the irradiation dose (1–50 kGy). The calorimetric curves of the copolymers synthesized showed a glass transition temperature (T_g) at 333 ± 10 K. The enthalpies of melting and crystallization decreased with increasing degree of grafting. The data from wide angle X-ray analysis indicated an increase of the amorphous part with degree of grafting. At lower grafting degrees of poly(acrylic acid) and poly(4-vinylpyridine) (up to 15%) onto PTFE matrix, the size of the crystallites was found to increase. The penetration of the grafted functional monomer leads to partial deorientation of the initial LDPE film.     

Biodegradable polymers. II. Degradation characteristics of hydrolysis-sensitive poly[(organo)phosphazenes].

Polyphosphazenes with hydrolytic labile substituents have potential as biodegradable materials. By proper choice of the substituents, polymers can be prepared which can degrade to harmless products. The rate of biodegradation and the nature of the degradation products can be widely varied by changing the chemical composition of the polymers. The degradation properties of a series of new polyphosphazene derivatives are discussed. The synthesis of phosphazene polymers with variable amounts of ethyl 2-(O-glycyl)lactate or ethyl 2-(O-alanyl)lactate as cosubstituents was described previously. These polymers were prepared by partial reaction of poly[(dichloro)phosphazene] with the corresponding amine compound. Total halogen replacement was achieved by subsequent introduction of glycine ethyl ester cosubstituents. The degradation characteristics of these polymers in organic solution or in vitro was investigated. It was demonstrated that the introduction of hydrolysis-sensitive side-groups along the polymer chain results in an increased degradability of the poly[(amino acid ester)phosphazenes]. A plausible mechanism for the hydrolysis of these materials is proposed. The main hydrolysis pathway of poly[(amino acid ester)phosphazene] devices in vitro involves release of the amino acid ester side-group followed by hydrolysis of the ester with formation of the amino acid and ethanol. Initial hydrolysis of the ester bond with subsequent release of glycine cannot be excluded but is probably predominant.     

Grafting sulfobetaine monomer onto the segmented poly(ether-urethane) surface to improve hemocompatibility

Polyurethanes are widely used as blood-contacting biomaterials, due to their good biocompatibility and mechanical properties. Nevertheless, their blood compatibility is still not adequate for more demanding applications. Surface modification is an effective way to improve the hemocompatibility for biomaterials. The purpose of the present study was to synthesize a novel nonthrombogenic biomaterial by modifying the surface of polyurethane. Ozonization was used to introduce active peroxide groups onto the segmented poly(ether-urethane) (SPEU) film surface and graft polymerization of N,N'-dimethyl (methacryloyloxyethyl) ammonium propanesulfonate (DMAPS), a sulfobetaine structure, onto the ozone-activated SPEU surface was conducted. The SPEU-g-PDMAPS film was characterized by ATR-FTIR, XPS, and contact angle measurements. ATR-FTIR and XPS confirmed the graft polymerization. The grafted film possessed a relatively hydrophilic surface, as revealed by contact angle measurement. The blood compatibility of the grafted films was evaluated by a platelet-rich plasma (PRP) adhesion study and scanning electron microscopy, using SPEU film as the reference. No platelet adhesion was observed for the grafted films incubated with PRP at 37 degrees C for 60 and 180 min. This new sulfobetaine structure grafted biomaterial might have potential for biomedical applications.