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Article ; Online: Gelation upon the Mixing of Amphiphilic Graft and Triblock Copolymers Containing Enantiomeric Polylactide Segments through Stereocomplex Formation.

Ohya, Yuichi / Yoshida, Yasuyuki / Kumagae, Taiki / Kuzuya, Akinori

2024 Volume 10, Issue 2

Abstract: Biodegradable injectable polymer (IP) systems that form hydrogels in situ when injected into the body have considerable potential as medical materials. In this paper, we report a new two-solution mixed biodegradable IP system that utilizes the ... ...

Abstract	Biodegradable injectable polymer (IP) systems that form hydrogels in situ when injected into the body have considerable potential as medical materials. In this paper, we report a new two-solution mixed biodegradable IP system that utilizes the stereocomplex (SC) formation of poly(l-lactide) (PLLA) and poly(d-lactide) (PDLA). We synthesized triblock copolymers of PLLA and poly(ethylene glycol), PLLA-
Language	English
Publishing date	2024-02-09
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2813982-3
ISSN	2310-2861 ; 2310-2861
ISSN (online)	2310-2861
ISSN	2310-2861
DOI	10.3390/gels10020139
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Development of immune cell delivery system using biodegradable injectable polymers for cancer immunotherapy.

Yoshizaki, Yuta / Horii, Kenta / Murase, Nobuo / Kuzuya, Akinori / Ohya, Yuichi

International journal of pharmaceutics

2024 Volume 652, Page(s) 123801

Abstract: Immune cell delivery using injectable hydrogel attracts much attention for improving its therapeutic effect. Specifically, dendritic cells (DCs) are the trigger cells for immune responses, and DC vaccines are studied for improving cancer immunotherapy. ... ...

Abstract	Immune cell delivery using injectable hydrogel attracts much attention for improving its therapeutic effect. Specifically, dendritic cells (DCs) are the trigger cells for immune responses, and DC vaccines are studied for improving cancer immunotherapy. Hydrogel-assisted cell delivery is expected to enhance the viability of the implanted cells. We recently reported temperature-responsive biodegradable injectable polymer (IP) formulation utilizing poly(ε-caprolactone-co-glycolide)-b-poly(ethylene glycol)(PEG)-b-poly(ε-caprolactone-co-glycolide) (tri-PCG). Tri-PCG-based IP was reported to exhibit immediate sol-to-gel transition in response to temperature increase, in vivo biodegradability, and excellent biocompatibility. In this study, tri-PCG-based IP was applied to DC delivery. IP encapsulated live DCs, and the DCs incorporated ovalbumin (OVA) as a model antigen and CpG-DNA (oligo DNA with adjuvant effect) in IP hydrogel. Results suggested that DCs encapsulated in IP hydrogel internalized OVA and CpG-DNA and DCs were maturated to present antigens to T cells. Moreover, subcutaneously injected tri-PCG-based IP prolonged the retention period of cell accumulation at injected sites. Tri-PCG IP hydrogel could release matured DCs as the degradation of the hydrogel progressed. Tri-PCG IP formulation improved treatment efficacy of OVA transfected mouse lymphoma (E.G7-OVA) tumor. Hence, tri-PCG IP is a promising platform for immune cell delivery.
MeSH term(s)	Mice ; Animals ; Polymers/metabolism ; Polyethylene Glycols ; Hydrogels ; Antigens ; DNA ; Dendritic Cells ; Immunotherapy ; Neoplasms/therapy ; Caproates ; Lactones
Chemical Substances	caprolactone (56RE988L1R) ; Polymers ; Polyethylene Glycols (3WJQ0SDW1A) ; Hydrogels ; Antigens ; DNA (9007-49-2) ; Caproates ; Lactones
Language	English
Publishing date	2024-01-19
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	428962-6
ISSN	1873-3476 ; 0378-5173
ISSN (online)	1873-3476
ISSN	0378-5173
DOI	10.1016/j.ijpharm.2024.123801
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Article ; Online: Temperature-responsive biodegradable injectable polymers with tissue adhesive properties.

Fujiwara, Soichiro / Yoshizaki, Yuta / Kuzuya, Akinori / Ohya, Yuichi

Acta biomaterialia

2021 Volume 135, Page(s) 318–330

Abstract: Injectable polymers (IPs) exhibiting in situ hydrogel formation have attracted attention as vascular embolization and postoperative adhesion prevention materials. While utilizing hydrogels for such purposes, it is essential to ensure that they have ... ...

Abstract	Injectable polymers (IPs) exhibiting in situ hydrogel formation have attracted attention as vascular embolization and postoperative adhesion prevention materials. While utilizing hydrogels for such purposes, it is essential to ensure that they have appropriate and controllable tissue adhesion property, as it is crucial for them to not detach from their deposited location in the blood vessel or abdominal cavity. Additionally, it is important to maintain gel state in vivo for the desired period at such locations, where large amounts of body fluid exist. We had previously reported on a biodegradable IP system exhibiting temperature-responsive gelation and subsequent covalent cross-link formation. We had utilized triblock copolymers of aliphatic polyester and poly(ethylene glycol) (tri-PCGs) and its derivative containing acrylate group at the termini (tri-PCG-Acryl), exhibiting a longer and more controllable duration time of the gel state. In this study, the introduction of aldehyde groups by the addition of aldehyde-modified Pluronic (PL-CHO) was performed for conferring controllable and appropriate tissue adhesive properties on these IP systems. The IP systems containing PL-CHO, which were not covalently incorporated into the hydrogel network, exhibited tissue adhesive properties through Schiff base formation. The adhesion strength could be controlled by the amount of PL-CHO added. The IP system showed good vascular embolization performance and pressure resistance in the blood vessels. The IP hydrogel remained at the administration site in the abdominal space for 2 days and displayed effective adhesion prevention performance. STATEMENT OF SIGNIFICANCE: Injectable polymers (IPs), which exhibit in situ hydrogel formation, are expected to be utilized as vascular embolization and postoperative adhesion prevention materials. The tissue adhesion properties of hydrogels are important for such applications. We succeeded in conferring tissue adhesion properties onto a previously reported IP system by mixing it with Pluronic modified with aldehyde groups (PL-CHO). The aldehyde groups allowed for the formation of Schiff bases at the tissue surfaces. The tissue adhesion property could be conveniently controlled by altering the amount of PL-CHO. We revealed that the in vitro embolization properties of IPs in blood vessels could be substantially improved by mixing with PL-CHO. The IP system containing PL-CHO also exhibited good in vivo performance for postoperative adhesion prevention.
MeSH term(s)	Hydrogels/pharmacology ; Polyethylene Glycols ; Polymers ; Temperature ; Tissue Adhesives
Chemical Substances	Hydrogels ; Polymers ; Tissue Adhesives ; Polyethylene Glycols (3WJQ0SDW1A)
Language	English
Publishing date	2021-08-28
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2173841-5
ISSN	1878-7568 ; 1742-7061
ISSN (online)	1878-7568
ISSN	1742-7061
DOI	10.1016/j.actbio.2021.08.033
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Article: Preparation of hyaluronic acid-coated polymeric micelles for nasal vaccine delivery

Suzuki, Kengo / Yoshizaki, Yuta / Horii, Kenta / Murase, Nobuo / Kuzuya, Akinori / Ohya, Yuichi

Biomaterials science. 2022 Apr. 12, v. 10, no. 8

2022

Abstract: Hyaluronic acid (HA)-coated biodegradable polymeric micelles were developed as nanoparticulate vaccine delivery systems to establish an effective nasal vaccine. We previously reported HA-coated micelles prepared by forming a polyion complex (PIC) of poly( ...

Abstract	Hyaluronic acid (HA)-coated biodegradable polymeric micelles were developed as nanoparticulate vaccine delivery systems to establish an effective nasal vaccine. We previously reported HA-coated micelles prepared by forming a polyion complex (PIC) of poly(l-lysine)-b-polylactide (PLys⁺-b-PLA) micelles and HA. The HA-coated micelles exhibited specific accumulation in HA receptor-expressing cells and extremely high colloidal stability under diluted blood conditions. In this study, a model antigen, ovalbumin (OVA), and an adjuvant oligonucleotide containing the CG motif (CpG–DNA) were efficiently loaded in HA-coated micelles via electrostatic interactions. HA-coated micelles delivered OVA and CpG–DNA in mouse bone marrow-derived dendritic cells (BMDCs) and resulted in the upregulation of mRNA encoding IFN-γ and IL-4 in BMDCs. In addition, HA-coated micelles enhanced the expression of the major histocompatibility complex (MHC) class II on BMDCs. We investigated the immune response of HA-coated micelles following intranasal administration. HA-coated micelles induced higher OVA-specific IgG in the blood and OVA-specific IgA in the nasal wash than control (carboxymethyl dextran-coated) micelles. These results suggest that HA-coated micelles efficiently deliver antigens and adjuvants to mucosal-resident immune cells. Therefore, HA-coated micelles are promising platforms for developing nasal vaccines against infectious diseases.
Keywords	adjuvants ; antigens ; biocompatible materials ; biodegradability ; blood ; hyaluronic acid ; immune response ; interleukin-4 ; intranasal administration ; lysine ; major histocompatibility complex ; mice ; micelles ; nose ; oligonucleotides ; ovalbumin ; polymers ; vaccines
Language	English
Dates of publication	2022-0412
Size	p. 1920-1928.
Publishing place	The Royal Society of Chemistry
Document type	Article
ZDB-ID	2693928-9
ISSN	2047-4849 ; 2047-4830
ISSN (online)	2047-4849
ISSN	2047-4830
DOI	10.1039/d1bm01985f
Database	NAL-Catalogue (AGRICOLA)

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Article: Versatile Cell-Specific Ligand Arrangement System onto Desired Compartments of Biodegradable Matrices for Site-Selective Cell Adhesion Using DNA Tags

Sumida, Hiromichi / Yoshizaki, Yuta / Kuzuya, Akinori / Ohya, Yuichi

Biomacromolecules. 2020 July 27, v. 21, no. 9

2020

Abstract: A promising approach for the regeneration of tissues or organs with three-dimensional hierarchical structures is the preparation of scaffold-cell complexes that mimic these hierarchical structures. This requires an effective technique for immobilizing ... ...

Abstract	A promising approach for the regeneration of tissues or organs with three-dimensional hierarchical structures is the preparation of scaffold-cell complexes that mimic these hierarchical structures. This requires an effective technique for immobilizing cell-specific ligands at arbitrarily chosen positions on matrices. Here, we report a versatile system for arranging cell-specific ligands onto desired compartments of biodegradable matrices for site-selective cell arrangement. We utilized the specific binding abilities of specific DNAs, immobilizing them as tags to arrange cell-recognition ligands at desired areas of the matrices by specific binding with cell-recognition ligand–DNA conjugates. We synthesized poly(l-lactide) (PLLA), a biodegradable polymer, with an oligo-DNA (trimer of deoxyguanosine: dG₃) attached via a poly(ethylene glycol) (PEG) spacer to generate dG₃-PEG-b-PLLA. The peptides Arg-Gly-Asp-Ser (RGDS) and Arg-Glu-Asp-Val (REDV) were chosen as cell-recognition ligands and were attached to an adapter DNA (aDNA), which can specifically bind to the dG₃ moiety through G-quadruplex formation. The obtained dG₃-PEG-b-PLLA was deposited on a small spot of the PLLA film, and the aDNA–RGDS or aDNA–REDV conjugate was added on the film to immobilize these ligands at the spot. We confirmed the specific adhesion of L929 cells (a mouse fibroblast cell line) and human umbilical vein endothelial cells (HUVECs) on the small areas coated with dG₃-PEG-b-PLLA in the presence of aDNA–RGDS and aDNA–REDV, respectively, even after applying shear stress by flowing medium across the spot. Cell-specific attachment of the target cells was effectively achieved in a spatially controlled manner. This technique has the potential for the construction of cell–scaffold complexes that mimic the hierarchical structures of natural organs and may represent a breakthrough in realizing regenerative medicine and tissue engineering of complex organs.
Keywords	DNA ; adhesion ; biodegradability ; cell adhesion ; cell lines ; fibroblasts ; ligands ; medicine ; mice ; moieties ; peptides ; shear stress
Language	English
Dates of publication	2020-0727
Size	p. 3713-3723.
Publishing place	American Chemical Society
Document type	Article
Note	NAL-AP-2-clean
ISSN	1526-4602
DOI	10.1021/acs.biomac.0c00814
Database	NAL-Catalogue (AGRICOLA)

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Article: Small-Diameter Synthetic Vascular Graft Immobilized with the REDV Peptide Reduces Early-Stage Fibrin Clot Deposition and Results in Graft Patency in Rats

Mahara, Atsushi / Li, Minglun / Ohya, Yuichi / Yamaoka, Tetsuji

Biomacromolecules. 2020 July 10, v. 21, no. 8

2020

Abstract: Early-stage hemocompatibility is indispensable for manufacturing tissue-engineered vascular grafts used in regenerative medicine. In this study, we report the in vivo blood response and patency of small-diameter synthetic vascular grafts modified with ... ...

Abstract	Early-stage hemocompatibility is indispensable for manufacturing tissue-engineered vascular grafts used in regenerative medicine. In this study, we report the in vivo blood response and patency of small-diameter synthetic vascular grafts modified with the Arg-Glu-Asp-Val (REDV) peptide. Vascular grafts were prepared by casting REDV-conjugated poly(depsipeptide-co-caprolactone) on a stainless-steel mandril (diameter: 1.8 mm). After implanting the grafts into the abdominal aorta of rats for 24 h, all three control grafts without the peptide and three out of the four REDV (control sequence) peptide-modified grafts showed occlusion. The luminal surfaces of these grafts were covered with thick thrombi. In contrast, all the grafts containing the REDV peptide were patent, and their luminal surfaces were covered with a thin layer of fibrin. These results indicated that the REDV peptide on the luminal surface effectively reduced early-stage fibrin clot deposition and formed the pseudo-endothelium layer in a peptide sequence-specific manner, resulting in graft patency.
Keywords	aorta ; biocompatibility ; fibrin ; medicine ; peptides ; stainless steel
Language	English
Dates of publication	2020-0710
Size	p. 3092-3101.
Publishing place	American Chemical Society
Document type	Article
Note	NAL-AP-2-clean
ISSN	1526-4602
DOI	10.1021/acs.biomac.0c00457
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Versatile Cell-Specific Ligand Arrangement System onto Desired Compartments of Biodegradable Matrices for Site-Selective Cell Adhesion Using DNA Tags.

Sumida, Hiromichi / Yoshizaki, Yuta / Kuzuya, Akinori / Ohya, Yuichi

Biomacromolecules

2020 Volume 21, Issue 9, Page(s) 3713–3723

Abstract	A promising approach for the regeneration of tissues or organs with three-dimensional hierarchical structures is the preparation of scaffold-cell complexes that mimic these hierarchical structures. This requires an effective technique for immobilizing cell-specific ligands at arbitrarily chosen positions on matrices. Here, we report a versatile system for arranging cell-specific ligands onto desired compartments of biodegradable matrices for site-selective cell arrangement. We utilized the specific binding abilities of specific DNAs, immobilizing them as tags to arrange cell-recognition ligands at desired areas of the matrices by specific binding with cell-recognition ligand-DNA conjugates. We synthesized poly(l-lactide) (PLLA), a biodegradable polymer, with an oligo-DNA (trimer of deoxyguanosine: dG
MeSH term(s)	Animals ; Cell Adhesion ; DNA ; Ligands ; Mice ; Polyethylene Glycols ; Tissue Engineering
Chemical Substances	Ligands ; Polyethylene Glycols (3WJQ0SDW1A) ; DNA (9007-49-2)
Language	English
Publishing date	2020-08-06
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1526-4602
ISSN (online)	1526-4602
DOI	10.1021/acs.biomac.0c00814
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Small-Diameter Synthetic Vascular Graft Immobilized with the REDV Peptide Reduces Early-Stage Fibrin Clot Deposition and Results in Graft Patency in Rats.

Mahara, Atsushi / Li, Minglun / Ohya, Yuichi / Yamaoka, Tetsuji

Biomacromolecules

2020 Volume 21, Issue 8, Page(s) 3092–3101

Abstract: Early-stage hemocompatibility is indispensable for manufacturing tissue-engineered vascular grafts used in regenerative medicine. In this study, we report ... ...

Abstract	Early-stage hemocompatibility is indispensable for manufacturing tissue-engineered vascular grafts used in regenerative medicine. In this study, we report the
MeSH term(s)	Animals ; Blood Vessel Prosthesis ; Fibrin ; Peptides/pharmacology ; Rats ; Thrombosis/drug therapy ; Vascular Grafting
Chemical Substances	Peptides ; Fibrin (9001-31-4)
Language	English
Publishing date	2020-07-22
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1526-4602
ISSN (online)	1526-4602
DOI	10.1021/acs.biomac.0c00457
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Article ; Online: Preparation of hyaluronic acid-coated polymeric micelles for nasal vaccine delivery.

Suzuki, Kengo / Yoshizaki, Yuta / Horii, Kenta / Murase, Nobuo / Kuzuya, Akinori / Ohya, Yuichi

Biomaterials science

2022 Volume 10, Issue 8, Page(s) 1920–1928

Abstract	Hyaluronic acid (HA)-coated biodegradable polymeric micelles were developed as nanoparticulate vaccine delivery systems to establish an effective nasal vaccine. We previously reported HA-coated micelles prepared by forming a polyion complex (PIC) of poly(L-lysine)-
MeSH term(s)	Adjuvants, Immunologic/pharmacology ; Animals ; Antigens ; DNA/pharmacology ; Dendritic Cells ; Histocompatibility Antigens Class II ; Hyaluronic Acid/pharmacology ; Mice ; Micelles ; Ovalbumin ; Polymers/pharmacology ; Vaccines
Chemical Substances	Adjuvants, Immunologic ; Antigens ; Histocompatibility Antigens Class II ; Micelles ; Polymers ; Vaccines ; Hyaluronic Acid (9004-61-9) ; Ovalbumin (9006-59-1) ; DNA (9007-49-2)
Language	English
Publishing date	2022-04-12
Publishing country	England
Document type	Journal Article
ZDB-ID	2693928-9
ISSN	2047-4849 ; 2047-4830
ISSN (online)	2047-4849
ISSN	2047-4830
DOI	10.1039/d1bm01985f
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Synthesis of Topological Gels by Penetrating Polymerization Using a Molecular Net.

Ohya, Yuichi / Dohi, Ryota / Seko, Fumika / Nakazawa, Yuto / Mizuguchi, Ken-Ichiro / Shinzaki, Kosei / Yasui, Takahiko / Ogawa, Hiroaki / Kato, Shizuka / Yoshizaki, Yuta / Murase, Nobuo / Kuzuya, Akinori

Angewandte Chemie (International ed. in English)

2024 Volume 63, Issue 11, Page(s) e202317045

Abstract: Topological gels possess structures that are cross-linked only via physical constraints; ideally, no attractive intermolecular interactions act between their components, which yields interesting physical properties. However, most reported previous ... ...

Abstract	Topological gels possess structures that are cross-linked only via physical constraints; ideally, no attractive intermolecular interactions act between their components, which yields interesting physical properties. However, most reported previous topological gels were synthesized based on supramolecular interlocked structures such as polyrotaxane, for which attractive intermolecular interactions are essential. Here, we synthesize a water-soluble "molecular net" (MN) with a large molecular weight and three-dimensional network structure using poly(ethylene glycol). When a water-soluble monomer (N-isopropylacrylamide) is polymerized in the presence of the MNs, the extending polymer chains penetrates the MNs to form an ideal topological MN gel with no specific attractive interactions between its components. The MN gels show unique physical properties as well a significantly high degree of swelling and high extensibility due to slipping of the physical cross-linking. We postulate this method to yield a new paradigm in gel science with unprecedented physical properties.
Language	English
Publishing date	2024-01-24
Publishing country	Germany
Document type	Journal Article
ZDB-ID	2011836-3
ISSN	1521-3773 ; 1433-7851
ISSN (online)	1521-3773
ISSN	1433-7851
DOI	10.1002/anie.202317045
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