Masahiko Minoda

Apatite-forming ability of carboxyl group-containing polymer gels in a simulated body fluid

Carboxymethylated chitin, gellan gum, and curdlan gels were soaked in a simulated body fluid (SBF) having ion concentrations nearly equal to those of human blood plasma. Some of the gels had been soaked in a saturated Ca(OH)(2) solution, while others had not. The carboxymethylated chitin and gellan gum gels have carboxyl groups, while the curdlan gel has hydroxyl groups. None of the gels formed apatite on their surfaces in the SBF when they had not been subjected to the Ca(OH)(2) treatment, whereas the carboxymethylated chitin and gellan gum gels formed apatite on their surfaces when they had been subjected to the Ca(OH)(2) treatment. The curdlan gel did not form an apatite deposit even after the Ca(OH)(2) treatment. Apatite formation on the carboxymethylated chitin and gellan gum gels was attributed to the catalytic effect of their carboxyl groups for apatite nucleation, and acceleration of apatite nucleation from released Ca(2+) ions. This result provides a guiding principle for obtaining apatite-organic polymer fiber composites. This composite is expected to have an analogous structure to that of natural bone.

Bonelike apatite formation on ethylene-vinyl alcohol copolymer modified with silane coupling agent and calcium silicate solutions

An ethylene-vinyl alcohol copolymer (EVOH) was treated with a silane coupling agent and calcium silicate solutions, and then soaked in a simulated body fluid (SBF) with ion concentrations approximately equal to those of human blood plasma. A smooth and uniform bonelike apatite layer was successfully formed on both the EVOH plate and the EVOH-knitted fibers in SBF within 2 days. Part of the structure of the resulting apatite-EVOH fiber composite was similar to that of natural bone. If this kind of composite can be fabricated into a three-dimensional structure similar to natural bone, the resultant composite is expected to exhibit both mechanical properties analogous to those of natural bone and bone-bonding ability. Hence, it has great potential as a bone substitute.

Reaction characteristics of cellulose in the LiCl/1,3‐dimethyl‐2‐imidazolidinone solvent system

In order to elucidate the nature of the LiCl/1,3‐dimethy‐2‐imidazolidinone (DMI) solvent system as one of the homogeneous reaction media of cellulose, cellulose acetate (CA) and O‐methylcellulose (MC) were prepared using this solvent system, and the distribution of substituents within anhydroglucose units was examined by 13C‐NMR. It was found that (i) homogeneous cellulose solutions can be easily prepared by heating 2, 5–12 and 100 parts of weight of cellulose, LiCl, and DMI, respectively, and (ii) the relative reactivity of hydroxyl groups is in the order C‐6 > C‐2 > C‐3 for both CA and MC. A remarkable feature of this solvent system is that the reaction efficiency in etherification is very high compared with other homogeneous solvent systems.

Controlled synthesis of glycopolymers with pendant D-glucosamine residues by living cationic polymerization

D-Glucosamine-containing glycopolymers with well-controlled structure were synthesized by living cationic polymerization. To this end, D-glucosamine-containing vinyl ether(VE) of the type [CH 2 =CH(OCH 2 CH 2 OR)] was prepared, where R denotes a 3,4,6-tri-O-acetyl-2-deoxy-2-phthalimide-β-D-glucopyranoside, i.e., the hydroxyl and amino groups in D-glucosamine residues are protected by acetyl and phthaloyl groups, respectively. It was found that (1) the efficient living cationic polymerization of VE monomer is achieved by a combination of ethylaluminum dichloride (EtAlC1 2 ) with an adduct of trifluoroacetic acid (TFA) and isobutyl VE (IBVE) [CH 3 CH(OiBu)OCOCF 3 ] (i.e., TFA/EtAlC1 2 initiating system); and (2) the polymerization in toluene at the elevated temperature (0°C ) is most suitable to proceed the homogeneous polymerization over the whole conversion range. The molecular weight distribution of the resulting polymers was very narrow (M ω /M n ∼1.1). Quantitative deprotection of the resulting precursor polymers was successfully achieved with hydrazine monohydrate to afford the corresponding water-soluble polymers with pendant D-glucosamine residues.

Controlled synthesis of amphiphilic block copolymers with pendant glucose residues by living cationic polymerization

Amphiphilic block copolymers of vinyl ethers (VEs) of the type —[CH2CH(OCH2CH2OR)]m—[CH2CH(OiBu)]n—were synthesized by living cationic polymerization, where R is a D-glucose residue, and m and n are the degrees of polymerization (m = 20–50; n = 11–89). To obtain them, sequential living block copolymerization of isobutyl vinyl ether (IBVE) and the vinyl ether carrying 1,2:5,6-diisopropylidene-D-glucose residue was conducted by using the HCl adduct of IBVE, CH3CH(OiBu)Cl, as initiator in conjunction with zinc iodide. These precursor block copolymers had a narrow molecular weight distribution (Mw/Mn ∼ 1.1) and a controlled composition. Treatment of them with a trifluoroacetic acid/water mixture led to the target amphiphiles. The solubility of the amphiphilic block copolymers in various solvents depended strongly on composition or the m/n ratio. Their solvent-cast thin films were observed, under a transmission electron microscope, to exhibit various microphase-separated surface morphologies such as spheres, cylinders, and lamellae, depending on composition.

Apatite formation on ethylene-vinyl alcohol copolymer modified with silanol groups

The surfaces of ethylene-vinyl alcohol copolymer (EVOH) substrates were modified with silanol (Si-OH) groups, and their apatite forming ability was examined in a simulated body fluid (SBF) with ion concentrations nearly equal to those of human blood plasma or in a solution with ion concentrations 1.5 times those of SBF (1.5SBF). The surface modification of EVOH was carried out by reacting 3-isocyanatopropyltriethoxysilane, followed by hydrolysis of the ethoxysilyl groups into Si-OH groups. However, no apatite formation was observed on the EVOH substrate thus modified, even after 3 weeks in SBF and 1.5SBF. The Si-OH modified EVOH substrate was further modified by hydrolysis and polycondensation of tetraethyoxysilane (TEOS). It was found that the apatite forms on the TEOS-modified substrate within 3 weeks in 1.5SBF. These results suggest that the presence of a large amount of Si-OH groups (i.e., a cluster of Si-OH groups) on the substrate is prerequisite to apatite formation in the body environment. Apatite-EVOH composites prepared by this process might be useful as hard tissues substitutes.

Apatite-forming ability of alginate fibers treated with calcium hydroxide solution.

Calcium alginate fibers were prepared by extruding an aqueous sodium alginate solution into an aqueous calcium chloride solution. The fibers were treated with a saturated aqueous calcium hydroxide solution for various periods and their apatite-forming ability was examined in a simulated body fluid (SBF). The calcium alginate fibers were treated with the aqueous calcium hydroxide solution for periods longer than five days formed apatite on their surfaces in SBF, and their apatite-forming ability improved with increasing calcium hydroxide treatment time. The amount of calcium ions released from the fibers also increased with increasing calcium hydroxide treatment time, resulting in acceleration of nucleation and growth of apatite on the fiber surfaces. The resultant apatite–alginate fiber composite is expected to be useful as a flexible bioactive bone-repairing material.

Biomimetic apatite formation on polyethylene photografted with vinyltrimethoxysilane and hydrolyzed

A photografting technique to produce functional groups of silanol able to induce apatite nucleation was attempted on polyethylene substrate for biomimetic formation of bone-mineral-like apatite layer on its surface. The polyethylene surface was subjected to vapor-phase photografting of vinyltrimethoxysilane and subsequently to hydrolysis. The photografting formed methoxysilyl groups on the polyethylene substrate, which was changed into silanol groups successively by the hydrolysis in a hydrochloric solution. The polyethylene modified in this way formed a dense and homogeneous bone-mineral-like apatite layer in a solution with ion concentrations 1.5 times that of human blood plasma. This result indicates that the biomimetic process in combination with a polymeric grafting technique might provide a homogeneous bone-mineral-like apatite coating even on polymer fibers to be woven into an apatite-polymer composite with three-dimensional structure analogous to that of natural bone.

Amphiphilic block and statistical copolymers with pendant glucose residues: Controlled synthesis by living cationic polymerization and the effect of copolymer architecture on their properties

Amphiphilic block and statistical copolymers of vinyl ethers (VEs) with pendant glucose residues were synthesized by the living cationic polymerization of isobutyl VE (IBVE) and a VE carrying 1,2:5,6-di-O-isopropylidene-D-glucose (IpGlcVE), followed by deprotection. The block copolymer was prepared by a two-stage sequential block copolymerization, whereas the statistical copolymer was obtained by the copolymerization of a mixture of the two monomers. The monomer reactivity ratios estimated with the statistical copolymerization were r 1 (IBVE) = 1.65 and r 2 (IpGlcVE) = 1.15. The obtained statistical copolymers were nearly uniform with the comonomer composition along the main chain. Both the block and statistical copolymers had narrow molecular weight distributions (weight-average molecular weight/number-average molecular weight ∼ 1.1). Gel permeation chromatography, static light scattering, and spin-lattice relaxation time measurements in a selective solvent revealed that the block copolymer formed multimolecular micelles, possibly with a hydrophobic poly(IBVE) core and a glucose-carrying poly(VE) shell, whereas the statistical copolymer with nearly the same molecular weight and segment composition was molecularly dispersed in solution. The surface properties of the solvent-cast films of the block and statistical copolymer were also investigated with the contact-angle measurement.

Living cationic polymerization of a vinyl ether with a triester pendant

SummaryCationic polymerization of CH2=CH-O-CH2CH2C(COOC2H5)3, a vinyl ether with three pendent esters, initiated by the HI/I2 system in toluene at −40 °C afforded living polymers with a controlled molecular weight (