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Biomedical subjects

Yuichi Ohya

Publications and source records attributed to Yuichi Ohya.

13 recordsLinked to original sources

Suppression of cell and platelet adhesion to star-shaped 8-armed poly(ethylene glycol)-poly(L-lactide) block copolymer films.

To explore the potential of a star-shaped 8-armed poly(ethylene glycol)35K-block-poly(L-lactide)37K (8-armed PEG35K-b-PLLA37K: M(n) of PEG = 35 000, M(n) of PLLA = 37 000) film as a novel bioabsorbable adhesion-prevention membrane, the water structure, surface contact angle, protein adsorption, and cell and platelet anti-adhesion properties of such a hydrated film are investigated. Based on the results, it is found that the 8-armed PEG35K-b-PLLA37K film exhibits a biologically inert surface, which is the result of a large number of PEG chains and a free water layer on the film surface. This leads to a reduction in protein absorption and cell and platelet adhesion onto the film surface. This implies that the star-shaped 8-armed PEG35K-b-PLLA37K film can be utilized as a novel bioabsorbable adhesion-prevention membrane.

Absorption↗

Thermosensitive biodegradable polydepsipeptide.

A poly(N-isopropylacrylamide) (PNIPAAm)-like biodegradable thermosensitive polydepsipeptide, poly[Glc-Asn(N-isopropyl)], was synthesized by introducing an isopropyl amide group into poly[Glc-Asn]. Poly[Glc-Asn(N-isopropyl)] was degraded in vitro by cleavage of the ester bonds in the main chain in water at room temperature. The non-toxic nature of the polymer and its degradation products, coupled with a cloud point at 29 degrees C in water, make this polymer attractive for biomedical implant applications.

Animals↗

Suppression of cell attachment and protein adsorption onto amphiphilic polylactide-grafted dextran films.

To develop novel biodegradable biomedical materials, polylactide-grafted dextrans (Dex-g-PLA)s having various lengths, numbers of graft chains and sugar units were synthesized using the trimethylsilyl (TMS) protection method. To explore the possibility of using Dex-g-PLA as a biomedical soft-material, the contact angle, cell attachment and protein adsorption properties of the films prepared from these biodegradable and amphiphilic graft co-polymers were investigated. The poly-L-lactide (PLLA) film did not absorb water at all because of its high hydrophobicity, while the graft co-polymer films started immediately to swell after immersion in PBS. The percentage of water absorption at equilibrium increased with increasing sugar unit content. The receding contact angle of the Dex-g-PLA films against water was smaller than that of the PLLA film. The receding contact angle of Dex-g-PLA films against water decreased with increasing the sugar unit content. The top surface of the Dex-g-PLA film was suggested to be covered with hydrophilic Dex segments by means of annealing in water and to afford the wettable surface. Such a wettable surface led to the suppression of cell attachment and protein adsorption onto the film.

Adsorption↗

Preparation of a hyaluronic acid hydrogel through polyion complex formation using cationic polylactide-based microspheres as a biodegradable cross-linking agent.

A novel hyaluronic acid (HA)-based hydrogel was prepared through polyion complex (PIC) formation between cationic polylactide (PLA)-based microspheres (MS+) and hyaluronic acid (HA-) as an anionic polyelectrolyte. The MS+ and HA formed a biodegradable PIC hydrogel (HA-/MS+) when mixed in aqueous media. The swelling behavior and mechanical properties of the PIC hydrogel could be controlled by changing the charge ratio between HA- and MS+. In addition, the HA-/MS+ PIC hydrogel resulted in a lower inflammatory response compared with a collagen hydrogel in vivo.

Animals↗

Encapsulation and/or release behavior of bovine serum albumin within and from polylactide-grafted dextran microspheres.

Polylactide (PLA)-grafted dextran (Dex-graft-PLA) of various contents of sugar units was synthesized by anionic polymerization of L-lactide (L-LA) using the alkoxide of partially trimethylsilylated dextran (TMSDex) and subsequently removing the trimethylsilyl (TMS) groups. The copolymer showed different solubility from L-LA homopolymer with increasing the content of sugar units. We prepared bovine serum albumin (BSA)-loaded microspheres (MS)s according to a water-in-oil-in-water emulsion-solvent evaporation/extraction method using methylene chloride/DMSO as an organic cosolvent. MSs prepared from Dex-graft-PLA [MS(Dex-graft-PLA)s] exhibited higher loading efficiency of BSA than MSs prepared from PLLA [MS(PLLA)s]. The in vitro release rate of BSA from MS(Dex-graft-PLA) was faster than that from MS(PLLA). BSA released from MS(Dex-graft-PLA) maintained the secondary structure of native BSA to a great extent, compared with BSA released from MS(PLLA).

Capsules↗

Preparation of a biodegradable matrix through polyion complex formation by mixing polylactide-based microspheres having oppositely charged surfaces.

The aggregation of polyions into microsphere (MS) complexes was studied as a preparative method for the construction of a biodegradable matrix. Aqueous suspensions of polylactide (PLA)-based MSs with positively and negatively charged surfaces, MS(K(3)(4+)-PLA) and MS(E(3)(4-)-PLA), respectively, immediately formed aggregates when mixed. The effects of the stoichiometry of the charged groups on the surfaces of the MSs and the ionic strength of the medium on aggregate formation, as well as the degradation behavior of the polyion complex (PIC) matrix over time, were investigated.

Absorption↗

Design of attachment type of drug delivery system by complex formation of avidin with biotinyl drug model and biotinyl saccharide.

Recent studies have focused on the active targeting of drug delivery by combining a homing device and antitumor drug. For this purpose, synthesis of a well-designed vehicle (such as polymer/drug conjugates or nanoparticles) carrying a drug and a homing device requires many steps. We propose a new type of drug delivery system (DDS) by formation of a complex containing avidin (Av) plus biotinyl drug with a biotinyl homing device, which easily accommodates the combination of various drugs and homing devices. The targetable drug complex can be prepared by selecting an appropriate biotinyl drug derivative and a biotinyl homing device and mixing them with avidin. Fluorescent dye with 5-(and-6)-carboxytetramethylrhodamine (TAMRA) was used as a drug model, and galactose (Gal) recognized by liver parenchymal cells was used as a homing device. TAMRA and galactose were attached to biotin (Bio) through a triethyleneglycol (TEG) spacer group to give Bio-TEG-TAMRA conjugate and Bio-TEG-Gal conjugate, respectively. Confocal laser scanning microscopic studies suggest that the complexes prepared by mixing Bio-TEG-Gal conjugate and fluorescein isothiocyanate (FITC)-labeled Av (feed molar ratio 4:1), and mixing Bio-TEG-Gal conjugate, Bio-TEG-TAMRA conjugate and FITC-labeled Av are internalized into the hepatoma cells through a receptor-mediated endocytosis mechanism.

Avidin↗

Cell growth on the porous sponges prepared from poly(depsipeptide-co-lactide) having various functional groups.

In tissue engineering, excellent biodegradable materials are desired as temporary scaffolds to support cell growth and disappear with the progress of tissue regeneration. We previously synthesized biodegradable poly(depsipeptide-co-lactide), poly[(Glc-Asp)-co-LA] and poly[(Glc-Lys)-co-LA], having reactive side-chain groups. Then, the effects of reactive and ionic side-chain groups on cell attachment and growth were investigated using co-polymer films with various amounts of carboxyl or amino groups. In this study, to evaluate the utility of these co-polymers as functional scaffolds for tissue regeneration, 3-dimensional porous sponges were prepared by freeze-drying method and the effects of reactive and ionic side-chain groups on cell growth and degradation behavior were investigated using co-polymer sponges with various amounts of carboxyl or amino groups. Good cell growth was observed on the co-polymer sponges. During cell culture, the co-polymer sponges exhibited various degradation rates related to the depsipeptide unit content. Three-dimensional biodegradable polymer matrices with reactive surface, controllable degradation behavior and good cell growth were successfully prepared using these co-polymers. Such kinds of co-polymer matrices are good candidate for scaffold for tissue engineering.

Absorbable Implants↗

Cell attachment and growth on films prepared from poly(depsipeptide-co-lactide) having various functional groups.

In tissue engineering related to the regeneration of damaged or lost tissue, excellent biodegradable materials are desired as temporary scaffolds to support cell growth and then disappear with the progress of tissue regeneration. We previously synthesized biodegradable poly(depsipeptide-co-lactide), poly[(Glc-Asp)-co-LA], and poly[(Glc-Lys)-co-LA] with reactive side-chain groups. In this study, to evaluate the utility of these copolymers as functional scaffolds for tissue regeneration, the effects of reactive and ionic side-chain groups on cell attachment and growth were investigated using copolymer films with various numbers of carboxyl or amino groups. Poly[(Glc-Lys)-co-LA] and poly[(Glc-Asp)-co-LA] films having appropriate positive or negative charges exhibited higher cell attachment ability than did poly-L-lactide. Good cell growth was observed on the copolymer films. During cell culture, the copolymer films exhibited higher degradation rates related to the depsipeptide content. Biodegradable polymer matrices with reactive surfaces for cell growth successfully were prepared using copolymers with various numbers of depsipeptide units. Varying the depsipeptide unit numbers in the copolymer could change the degradation rate of these matrices.

Animals↗

Multistep fluorescence resonance energy transfer in sequential chromophore array constructed on oligo-DNA assemblies.

Sequential arrays of chromophores at regulated distances were constructed on a noncovalent DNA molecular assembly system in aqueous media. Photoinduced fluorescence resonance energy transfer (FRET) behaviors were then observed. We designed a number of chromophore/oligo-DNA conjugates with varying sequences. The chromophores eosin (Eo), TexasRed (TR), and tetramethylrhodamine (Rho) were employed as the energy donor, acceptor, and mediator, respectively, based on overlapping excitation and emission spectra. The chromophores were attached via aminolinkers to the 5'-terminals of 10mer oligo-DNAs consisting of AT rich sequences. The arrangement of Eo-Rho or Rho-TR with 10-residue (1 pitch of duplex) distances was ensured by duplex formation of the conjugates with a 20mer matrix oligo-DNA composed of complementary sequences to the conjugates. Single-step FRET from Eo to Rho and from Rho to TR was confirmed on the duplex. The three chromophore conjugates were then mixed with longer matrix oligo-DNAs (30 or 40mer) consisting of complementary sequences to the conjugates, producing Eo-(Rho)(n)-TR (n = 1 or 2) arrays with 10-residue distances. Multistep FRET from Eo to TR through the Rho mediator(s) was observed on the molecular assemblies. This photoenergy transmission system offers a good model for a photoenergy transmission system mimicking photosynthetic systems.

Base Sequence↗

Preparation of poly(L-lactide)-based microspheres having a cationic or anionic surface using biodegradable surfactants.

Poly(L-lactide)-based microspheres having cationic or anionic surfaces were prepared using polydepsipeptide-block-poly(L-lactide)s as surfactants. Polydepsipeptide-block-poly(L-lactide)s having amino or carboxylic acid groups on their side chains were synthesized through anionic ring-opening polymerizations of L-lactide using the corresponding protected polydepsipeptides as macroinitiators and consequent deprotections. Since these amphiphilic copolymers consisting of hydrophobic segments and hydrophilic segments with amino or carboxylic acid groups could be converted to cationic or anionic block copolymers, they could act as surfactants preparing poly(L-lactide)-based microspheres by an oil-in-water emulsion method. The amount of ionic groups located on the surfaces of the obtained microspheres was found to increase with increasing the feed of charged polydepsipeptide-block-poly(L-lactide)s in the blend of poly(L-lactide) and block copolymers. The average diameters of the dried microspheres estimated by scanning electron microscopy were found to decrease with an increase in feed of block copolymers in polymer blends.

Anions↗

Synthesis of poly(L-lactide) end-capped with lactose residue.

The synthesis of poly(L-lactide) (polyLA) end-capped with lactose residue was studied from the standpoint of development of a new bioabsorbable material. After the hydroxyl group of t-butoxycarbonyl(Boc)-aminoethanol was converted to Boc-aminoethanol-OK by using potassium/naphthalene, L-lactide was polymerized in tetrahydrofuran using Boc-aminoethanol-OK as an initiator at room temperature to prepare polyLA-NHBoc. Subsequently, the removal of the Boc group in terminal Boc-aminoethanol residue was performed by treatment of formic acid to obtain the amino group end-capped polyLA (polyLA-NH(2)) as a reactive polyLA derivative. The coupling reactions of lactose with polyLA-NH(2) were investigated by two methods; the synthetic method through reductive amination of lactose with polyLA-NH(2) in the presence of sodium cyanoborohydride as a reducing agent did not give high degree of substitution of end-capped lactose residue per polyLA molecule, whereas the synthetic method through the ester interchange reaction of lactonolactone with polyLA-NH(2) gave Lac-polyLA perfectly end-capped with lactose residue.

Amination↗

Formation of core-shell type biodegradable polymeric micelles from amphiphilic poly(aspartic acid)-block-polylactide diblock copolymer.

Poly(aspartic acid)-block-polylactide diblock copolymers (PAsp-b-PLAs) having both hydrophilic and hydrophobic segments of various lengths were synthesized. These PAsp-b-PLA diblock copolymers formed polymeric micelles consisting of a hydrophobic PLA core and a hydrophilic, pH-sensitive PAsp shell in aqueous solution. The effects of the segment length of both the PLA and the PAsp portions and the pH of the solution on the shapes and sizes of the PAsp-b-PLA polymeric micelles were investigated. The results indicated a balance between the effects of electrostatic repulsion, hydrogen bonding in the PAsp shell layer, and hydrophobic interactions in the PLA core determine the sizes of the PAsp-b-PLA polymeric micelles. Moreover, the PAsp-b-PLA polymeric micelles did not possess any cytotoxic activity against L929 fibroblast cells. The obtained polymeric micelle should be useful for biodegradable biomedical materials such as drug delivery vehicle.

Biocompatible Materials↗