The Experts below are selected from a list of 291 Experts worldwide ranked by ideXlab platform
Sadahito Aoshima - One of the best experts on this subject based on the ideXlab platform.
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Desilylation-Triggered Degradable SilylAcetal Polymers Synthesized via Controlled Cationic Copolymerization of Trimethylsilyl Vinyl Ether and Cyclic Acetals
ACS Macro Letters, 2019Co-Authors: Ryusei Kato, Arihiro Kanazawa, Sadahito Aoshima, Arihiro Kanazawa, Sadahito AoshimaAbstract:SilylAcetal was demonstrated to function as a promising cleavable moiety for preparing polymers degradable via desilylation under diverse, mild conditions. The silylAcetal moieties were installed in the main chain of the polymers via the controlled cationic copolymerization of trimethylsilyl vinyl ether (TMSVE) and a Cyclic Acetal under appropriately designed conditions. Importantly, desilylation reactions of the silylAcetal units occurred under weak acid, base, or fluoride ion conditions, which triggered the degradation of the polymer via the spontaneous cleavage of the unstable hemiAcetal moieties generated by the desilylation. Moreover, silylAcetal moieties were successfully incorporated at the desired positions in the main chain via the addition of a small portion of TMSVE during the controlled cationic copolymerization of a vinyl ether and Cyclic Acetal. The strategy devised in this study will allow the design of elaborate polymers that undergo degradation triggered by various stimuli.
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Polyaddition of vinyl ethers and phthalaldehydes via successive cyclotrimerization reactions: selective model reactions and synthesis of acid-degradable linear poly(Cyclic Acetal)s
Polymer Chemistry, 2019Co-Authors: Tadashi Naito, Arihiro Kanazawa, Sadahito AoshimaAbstract:A polyaddition reaction via the cyclotrimerization of one vinyl ether and two conjugated dialdehyde molecules successfully proceeded using EtAlCl2 as a Lewis acid catalyst, yielding a polymer with Cyclic Acetal structures in the main chain. The use of a low-reactive or non-polymerizable vinyl ether and the choice of adequate catalysts were extremely important for the effective cyclotrimerization reactions. Diphenylethylene was also efficiently polymerized with dialdehydes. The polymers obtained by the polyaddition reaction showed selective acid-degradability and high glass-transition temperatures based on the Cyclic Acetal structures in the main chain.
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Controlled cationic copolymerization of vinyl monomers and Cyclic Acetals via concurrent vinyl-addition and ring-opening mechanisms: the systematic study of structural effects on the copolymerization behavior
Polymer Chemistry, 2019Co-Authors: Kazuya Maruyama, Arihiro Kanazawa, Sadahito AoshimaAbstract:The effects of the structure of Cyclic Acetals on their copolymerization with vinyl ethers (VEs) via concurrent vinyl-addition and ring-opening mechanisms were revealed through a systematic study using five-, six-, and seven-membered Cyclic Acetals with no substituents or one or two methyl substituents. The controlled cationic copolymerization of 2-chloroethyl vinyl ether (CEVE) and various Cyclic Acetals successfully proceeded in a living manner. Importantly, the copolymerization times (10 s–70 h) and the sequences of the copolymers (multiblock, random, or approximately alternating) significantly differed depending on the Cyclic Acetal used. An increase in the number of methyl substituents at the 2-position of the Cyclic Acetal improved the stability of the generated carbocation, which led to copolymerization with both frequent crossover reactions and at high polymerization rates. The ring member was responsible for the amount of ring strain and its Lewis basicity, which were also related to the frequency of the crossover reactions and the polymerization rates. The controlled copolymerization of Cyclic Acetals with isobutyl vinyl ether, which is a more reactive VE than CEVE, also proceeded, and the frequencies of the crossover reactions were lower. The key factors affecting the crossover reactions are discussed on the basis of the reactivities of the vinyl monomers and Cyclic Acetals.
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synthesis of highly defined graft copolymers using a Cyclic Acetal moiety as a two stage latent initiating site for successive living cationic polymerization and ring opening anionic polymerization
Macromolecules, 2018Co-Authors: Norifumi Yokoyama, Arihiro Kanazawa, Shokyoku Kanaoka, Sadahito AoshimaAbstract:The synthesis of well-defined graft copolymers with designed intervals between branches was achieved using Cyclic Acetal moieties as two-stage latent initiating sites. A Cyclic Acetal was shown to initiate the living cationic polymerization of vinyl ethers (VEs), yielding a polymer with a hydroxy group at the α-end derived from the Cyclic Acetal. The newly generated hydroxy group was able to efficiently induce the subsequent ring-opening anionic polymerization of l-lactide (LLA), and a diblock copolymer with a narrow molecular weight distribution (MWD) was obtained. For the synthesis of a graft copolymer, a five-membered Cyclic Acetal moiety was introduced at the ω-chain ends of poly(VE)s, which was employed as the initiating site for the living cationic polymerization of VEs. Repeated polymerization and Acetalization generated a macroinitiator with several hydroxy groups on the side chain of a poly(VE) backbone. Graft copolymers possessing branches with narrow MWDs and regular spaces between the branches...
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Synthesis of Highly Defined Graft Copolymers Using a Cyclic Acetal Moiety as a Two-Stage Latent Initiating Site for Successive Living Cationic Polymerization and Ring-Opening Anionic Polymerization
2018Co-Authors: Norifumi Yokoyama, Arihiro Kanazawa, Shokyoku Kanaoka, Sadahito AoshimaAbstract:The synthesis of well-defined graft copolymers with designed intervals between branches was achieved using Cyclic Acetal moieties as two-stage latent initiating sites. A Cyclic Acetal was shown to initiate the living cationic polymerization of vinyl ethers (VEs), yielding a polymer with a hydroxy group at the α-end derived from the Cyclic Acetal. The newly generated hydroxy group was able to efficiently induce the subsequent ring-opening anionic polymerization of l-lactide (LLA), and a diblock copolymer with a narrow molecular weight distribution (MWD) was obtained. For the synthesis of a graft copolymer, a five-membered Cyclic Acetal moiety was introduced at the ω-chain ends of poly(VE)s, which was employed as the initiating site for the living cationic polymerization of VEs. Repeated polymerization and Acetalization generated a macroinitiator with several hydroxy groups on the side chain of a poly(VE) backbone. Graft copolymers possessing branches with narrow MWDs and regular spaces between the branches were synthesized by the ring-opening polymerization of LLA using this macroinitiator
Arihiro Kanazawa - One of the best experts on this subject based on the ideXlab platform.
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Desilylation-Triggered Degradable SilylAcetal Polymers Synthesized via Controlled Cationic Copolymerization of Trimethylsilyl Vinyl Ether and Cyclic Acetals
ACS Macro Letters, 2019Co-Authors: Ryusei Kato, Arihiro Kanazawa, Sadahito Aoshima, Arihiro Kanazawa, Sadahito AoshimaAbstract:SilylAcetal was demonstrated to function as a promising cleavable moiety for preparing polymers degradable via desilylation under diverse, mild conditions. The silylAcetal moieties were installed in the main chain of the polymers via the controlled cationic copolymerization of trimethylsilyl vinyl ether (TMSVE) and a Cyclic Acetal under appropriately designed conditions. Importantly, desilylation reactions of the silylAcetal units occurred under weak acid, base, or fluoride ion conditions, which triggered the degradation of the polymer via the spontaneous cleavage of the unstable hemiAcetal moieties generated by the desilylation. Moreover, silylAcetal moieties were successfully incorporated at the desired positions in the main chain via the addition of a small portion of TMSVE during the controlled cationic copolymerization of a vinyl ether and Cyclic Acetal. The strategy devised in this study will allow the design of elaborate polymers that undergo degradation triggered by various stimuli.
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Polyaddition of vinyl ethers and phthalaldehydes via successive cyclotrimerization reactions: selective model reactions and synthesis of acid-degradable linear poly(Cyclic Acetal)s
Polymer Chemistry, 2019Co-Authors: Tadashi Naito, Arihiro Kanazawa, Sadahito AoshimaAbstract:A polyaddition reaction via the cyclotrimerization of one vinyl ether and two conjugated dialdehyde molecules successfully proceeded using EtAlCl2 as a Lewis acid catalyst, yielding a polymer with Cyclic Acetal structures in the main chain. The use of a low-reactive or non-polymerizable vinyl ether and the choice of adequate catalysts were extremely important for the effective cyclotrimerization reactions. Diphenylethylene was also efficiently polymerized with dialdehydes. The polymers obtained by the polyaddition reaction showed selective acid-degradability and high glass-transition temperatures based on the Cyclic Acetal structures in the main chain.
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Controlled cationic copolymerization of vinyl monomers and Cyclic Acetals via concurrent vinyl-addition and ring-opening mechanisms: the systematic study of structural effects on the copolymerization behavior
Polymer Chemistry, 2019Co-Authors: Kazuya Maruyama, Arihiro Kanazawa, Sadahito AoshimaAbstract:The effects of the structure of Cyclic Acetals on their copolymerization with vinyl ethers (VEs) via concurrent vinyl-addition and ring-opening mechanisms were revealed through a systematic study using five-, six-, and seven-membered Cyclic Acetals with no substituents or one or two methyl substituents. The controlled cationic copolymerization of 2-chloroethyl vinyl ether (CEVE) and various Cyclic Acetals successfully proceeded in a living manner. Importantly, the copolymerization times (10 s–70 h) and the sequences of the copolymers (multiblock, random, or approximately alternating) significantly differed depending on the Cyclic Acetal used. An increase in the number of methyl substituents at the 2-position of the Cyclic Acetal improved the stability of the generated carbocation, which led to copolymerization with both frequent crossover reactions and at high polymerization rates. The ring member was responsible for the amount of ring strain and its Lewis basicity, which were also related to the frequency of the crossover reactions and the polymerization rates. The controlled copolymerization of Cyclic Acetals with isobutyl vinyl ether, which is a more reactive VE than CEVE, also proceeded, and the frequencies of the crossover reactions were lower. The key factors affecting the crossover reactions are discussed on the basis of the reactivities of the vinyl monomers and Cyclic Acetals.
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synthesis of highly defined graft copolymers using a Cyclic Acetal moiety as a two stage latent initiating site for successive living cationic polymerization and ring opening anionic polymerization
Macromolecules, 2018Co-Authors: Norifumi Yokoyama, Arihiro Kanazawa, Shokyoku Kanaoka, Sadahito AoshimaAbstract:The synthesis of well-defined graft copolymers with designed intervals between branches was achieved using Cyclic Acetal moieties as two-stage latent initiating sites. A Cyclic Acetal was shown to initiate the living cationic polymerization of vinyl ethers (VEs), yielding a polymer with a hydroxy group at the α-end derived from the Cyclic Acetal. The newly generated hydroxy group was able to efficiently induce the subsequent ring-opening anionic polymerization of l-lactide (LLA), and a diblock copolymer with a narrow molecular weight distribution (MWD) was obtained. For the synthesis of a graft copolymer, a five-membered Cyclic Acetal moiety was introduced at the ω-chain ends of poly(VE)s, which was employed as the initiating site for the living cationic polymerization of VEs. Repeated polymerization and Acetalization generated a macroinitiator with several hydroxy groups on the side chain of a poly(VE) backbone. Graft copolymers possessing branches with narrow MWDs and regular spaces between the branches...
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Synthesis of Highly Defined Graft Copolymers Using a Cyclic Acetal Moiety as a Two-Stage Latent Initiating Site for Successive Living Cationic Polymerization and Ring-Opening Anionic Polymerization
2018Co-Authors: Norifumi Yokoyama, Arihiro Kanazawa, Shokyoku Kanaoka, Sadahito AoshimaAbstract:The synthesis of well-defined graft copolymers with designed intervals between branches was achieved using Cyclic Acetal moieties as two-stage latent initiating sites. A Cyclic Acetal was shown to initiate the living cationic polymerization of vinyl ethers (VEs), yielding a polymer with a hydroxy group at the α-end derived from the Cyclic Acetal. The newly generated hydroxy group was able to efficiently induce the subsequent ring-opening anionic polymerization of l-lactide (LLA), and a diblock copolymer with a narrow molecular weight distribution (MWD) was obtained. For the synthesis of a graft copolymer, a five-membered Cyclic Acetal moiety was introduced at the ω-chain ends of poly(VE)s, which was employed as the initiating site for the living cationic polymerization of VEs. Repeated polymerization and Acetalization generated a macroinitiator with several hydroxy groups on the side chain of a poly(VE) backbone. Graft copolymers possessing branches with narrow MWDs and regular spaces between the branches were synthesized by the ring-opening polymerization of LLA using this macroinitiator
John Fisher - One of the best experts on this subject based on the ideXlab platform.
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Characterization of Cyclic Acetal hydroxyapatite nanocomposites for craniofacial tissue engineering.
Journal of biomedical materials research. Part A, 2010Co-Authors: Minal Patel, Ketan J. Patel, John F. Caccamese, Domenick P. Coletti, John J. Sauk, John FisherAbstract:Cyclic Acetal hydrogels are a novel group of biomaterials which may facilitate osteogenic differentiation of encapsulated bone marrow stromal cells (BMSCs) because of their neutral degradation products. Here, we have incorporated hydroxyapatite nanoparticles within Cyclic Acetal hydrogels to create Cyclic Acetal nanocomposites for craniofacial tissue engineering applications. We hypothesized that inclusion of nanosized hydroxyapatite particles within Cyclic Acetal hydrogels would upregulate osteogenic signal expression of encapsulated BMSCs, due to enhanced cell adhesion, and therefore promote osteodifferentiation. Experimental nanocomposite groups consisted of lower (5 ng/mL) and higher (50 ng/mL) concentrations of nanoparticles. The nanocomposites were characterized by scanning electron microscopy, transmission electron microscopy, and energy dispersive spectroscopy. Swelling parameters of hydrogels in the presence of nanoparticles was studied. Osteoblastic differentiation was characterized by alkaline phosphatase (ALP) and osteocalcin (OC) expression, whereas endogenous osteogenic signal expression was characterized by morphogenetic protein-2 (BMP-2) expression. Finally, immunohistochemistry was performed to detect the presence of OC at the protein level. Results indicated that hydroxyapatite nanoparticles were uniformly distributed throughout the hydrogels and did not affect material properties of the gels. Viability of cells was not affected by nanoparticle concentration, and BMP-2 and OC mRNA expression was enhanced in the presence of nanoparticles. However, a difference in BMP-2, ALP, and OC mRNA expression was not noted between the lower and higher concentrations of nanoparticles. This work demonstrates that inclusion of hydroxyapatite nanoparticles within a Cyclic Acetal nanocomposite hydrogel may enhance BMSC differentiation by promoting endogenous osteogenic signal expression. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res 2010
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Cyclic Acetal hydroxyapatite nanocomposites for orbital bone regeneration.
Tissue engineering. Part A, 2010Co-Authors: Minal Patel, Ketan J. Patel, John F. Caccamese, Domenick P. Coletti, John J. Sauk, Martha W. Betz, Elyse Geibel, John FisherAbstract:We have incorporated hydroxyapatite nanoparticles within Cyclic Acetal hydrogels to create nanocomposites that can be used to repair surgically created orbital floor defects in a rabbit animal model. Nanosized hydroxyapatite particles may improve tissue engineering scaffold properties because they have similar length scale of many cellular and molecular components and therefore can enhance cellular adhesion and migration. We hypothesize that inclusion of nanosized hydroxyapatite particles (20–70 nm) within Cyclic Acetal hydrogels would support bone defect repair. The objectives of our study include (1) characterization of nanocomposites in vitro, (2) investigation of tissue response and capsule tissue surrounding nanocomposites in vivo, and (3) investigation of the potential of nanocomposites to facilitate bone formation at 7- and 28-day time points in vivo. Experimental nanocomposite groups consisted of 0, 10, and 50 ng/mL nanosized hydroxyapatite. In vitro results indicated uniform dispersion of nanopar...
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Cellular responses to degradable Cyclic Acetal modified PEG hydrogels
Journal of biomedical materials research. Part A, 2009Co-Authors: Sachiko Kaihara, Shuichi Matsumura, John FisherAbstract:In this study, high viability of bone marrow stromal stem cells (BMSCs) encapsulated in a synthetic, poly[poly(ethylene glycol)-co-Cyclic Acetal] (PECA) hydrogel has been reported. This novel degradable hydrogel, which contains Cyclic Acetal as degradable segments and poly(ethylene glycol) (PEG) as hydrophilic segments, has been designed to limit the release of acidic products during hydrolytic degradation. PECAs with three different molecular weights (PECA 600, 1000, and 2000) were prepared to evaluate the effect of polymer main chain molecular weight on the viability and morphology of BMSCs embedded in PECA hydrogels as well as the viability of BMSCs exposed to PECA degradation products. Results demonstrated high BMSC viability when incubated in control media with PECA, while a significant decrease in viability was noted after 4 days when incubated in media augmented with PEG diacrylate. There was no effect of PECA molecular weight on the differentiation and cytotoxicity of degradation products up to 4 days, indicating that the degradation products' terminal carbonyl groups do not significantly affect cell viability and differentiation. BMSC viability when embedded on PECA hydrogels was evaluated by a LIVE/DEAD assay, and confirmed high viability up to 14 days. Gene expression analysis confirmed that BMSCs embedded in PECA hydrogels undergo osteogenic differentiation. Histological analysis also showed that cell morphology was significantly influenced by hydrogel swelling degree, which is itself controllable by the molecular weights of PECA main chains. These results indicate that PECA hydrogels may be utilized as scaffolds for regeneration of bone-like tissues.
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Cyclic Acetal hydrogel system for bone marrow stromal cell encapsulation and osteodifferentiation
Journal of biomedical materials research. Part A, 2008Co-Authors: Martha W. Betz, John F. Caccamese, Domenick P. Coletti, John J. Sauk, Parth Modi, John FisherAbstract:Many systems have been proposed for the encapsulation of bone marrow stromal cells (BMSCs) within degradable hydrogels. Here, we use a novel Cyclic Acetal-based biomaterial formed from 5-ethyl-5-(hydroxymethyl)-β,β-dimethyl-1,3-dioxane-2-ethanol diacrylate (EHD) and poly(ethylene glycol) diacrylate (PEGDA). A Cyclic Acetal-based hydrogel may be preferred as Cyclic Acetals hydrolytically degraded into diols and carbonyls as primary degradation products, which may not affect local acidity, unlike other widely investigated polymers. The EHD monomer and PEGDA polymer may be fabricated into a EH-PEG hydrogel by radical polymerization initiated by the ammonium persulfate (APS) and N,N,N′,N′-tetramethylethylenediamine (TEMED) system. The objective of this work is to determine whether the components utilized in the fabrication of EH-PEG hydrogels as well as the EH-PEG hydrogels permit BMSC viability, metabolic activity, and osteodifferentiation. Cell viability and metabolic activity were assessed after 30 min, 1 h, and 3 h of exposure to pertinent concentrations of the initiator system (10–20 mM). Osteodifferentiation was assessed by alkaline phosphatase and osteocalcin expression after a short exposure to the initiator system to simulate the encapsulation process. Lastly, cell viability was assessed immediately after encapsulation and after 7 days of culture within the EH-PEG hydrogels. Results indicate that the metabolic activity and viability of BMSCs are minimally affected, and that osteodifferentiation is not significantly affected by the APS-TEMED initiator system. Also, encapsulated BMSCs maintained viability within EH-PEG hydrogels for 7 days. This work demonstrates that the EH-PEG hydrogel is a viable option for the encapsulation and osteodifferentiation of BMSCs. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res 2008
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Synthesis and characterization of Cyclic Acetal based degradable hydrogels
European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V, 2007Co-Authors: Sachiko Kaihara, Shuichi Matsumura, John FisherAbstract:While many synthetic, hydrolytically degradable hydrogels have been developed for biomedical applications, there are only a few examples whose polymer backbone does not form acidic products upon degradation. In order to address this concern, we proposed to develop a hydrogel based on a Cyclic Acetal unit that produces diols and propanals upon hydrolytic degradation. In particular, we proposed the fabrication of hydrogels formed by the free radical polymerization of two diacrylate monomers, 5-ethyl-5-(hydroxymethyl)-beta,beta-dimethyl-1,3-dioxane-2-ethanol diacrylate (EHD), a Cyclic Acetal having two acryl groups, and poly(ethylene glycol)diacrylate (PEGDA). However, the hydrophobicity of the EHD monomer inhibits hydrogel fabrication. Therefore this work develops a strategy to form hydrogels with a co-monomer system, one of which is hydrophobic, and subsequently describes the properties of the resulting hydrogel. Using benzoyl peroxide as an initiator and N,N-dimethyl-p-toluidine as an accelerator, the EHD and PEGDA monomers were reacted in an acetone/water co-solvent system. The chemical structure of the resulting EH-PEG [5-ethyl-5-(hydroxymethyl)-beta,beta-dimethyl-1,3-dioxane-2-ethanol-co-PEG] hydrogel was then characterized by FT-IR. Physicochemical properties of the EH-PEG hydrogel, including swelling degree, sol fraction, and contact angle, were determined so as to characterize the properties of these materials and ultimately investigate their use in drug delivery and tissue engineering applications. Results showed that EH-PEG hydrogel may be formed using the co-solvent system. Further results indicated that swelling degree is dependent upon initiator concentration, monomer concentration, and molar ratios of monomers, while sol fraction significantly depended on initiator concentration and monomer concentration, only. These results demonstrate the ability to fabricate hydrogels using EHD and PEGDA system as well as to control the properties of the resulting hydrophilic networks.
Norifumi Yokoyama - One of the best experts on this subject based on the ideXlab platform.
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synthesis of highly defined graft copolymers using a Cyclic Acetal moiety as a two stage latent initiating site for successive living cationic polymerization and ring opening anionic polymerization
Macromolecules, 2018Co-Authors: Norifumi Yokoyama, Arihiro Kanazawa, Shokyoku Kanaoka, Sadahito AoshimaAbstract:The synthesis of well-defined graft copolymers with designed intervals between branches was achieved using Cyclic Acetal moieties as two-stage latent initiating sites. A Cyclic Acetal was shown to initiate the living cationic polymerization of vinyl ethers (VEs), yielding a polymer with a hydroxy group at the α-end derived from the Cyclic Acetal. The newly generated hydroxy group was able to efficiently induce the subsequent ring-opening anionic polymerization of l-lactide (LLA), and a diblock copolymer with a narrow molecular weight distribution (MWD) was obtained. For the synthesis of a graft copolymer, a five-membered Cyclic Acetal moiety was introduced at the ω-chain ends of poly(VE)s, which was employed as the initiating site for the living cationic polymerization of VEs. Repeated polymerization and Acetalization generated a macroinitiator with several hydroxy groups on the side chain of a poly(VE) backbone. Graft copolymers possessing branches with narrow MWDs and regular spaces between the branches...
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Synthesis of Highly Defined Graft Copolymers Using a Cyclic Acetal Moiety as a Two-Stage Latent Initiating Site for Successive Living Cationic Polymerization and Ring-Opening Anionic Polymerization
2018Co-Authors: Norifumi Yokoyama, Arihiro Kanazawa, Shokyoku Kanaoka, Sadahito AoshimaAbstract:The synthesis of well-defined graft copolymers with designed intervals between branches was achieved using Cyclic Acetal moieties as two-stage latent initiating sites. A Cyclic Acetal was shown to initiate the living cationic polymerization of vinyl ethers (VEs), yielding a polymer with a hydroxy group at the α-end derived from the Cyclic Acetal. The newly generated hydroxy group was able to efficiently induce the subsequent ring-opening anionic polymerization of l-lactide (LLA), and a diblock copolymer with a narrow molecular weight distribution (MWD) was obtained. For the synthesis of a graft copolymer, a five-membered Cyclic Acetal moiety was introduced at the ω-chain ends of poly(VE)s, which was employed as the initiating site for the living cationic polymerization of VEs. Repeated polymerization and Acetalization generated a macroinitiator with several hydroxy groups on the side chain of a poly(VE) backbone. Graft copolymers possessing branches with narrow MWDs and regular spaces between the branches were synthesized by the ring-opening polymerization of LLA using this macroinitiator
J Fisher - One of the best experts on this subject based on the ideXlab platform.
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tissue response and orbital floor regeneration using Cyclic Acetal hydrogels
Journal of Biomedical Materials Research Part A, 2009Co-Authors: Martha W. Betz, John F. Caccamese, Domenick P. Coletti, John J. Sauk, J FisherAbstract:Orbital floor injuries are a common form of traumatic craniofacial injury that may not heal properly through the body's endogenous response. Reconstruction is often necessary, and an optimal method does not exist. We propose a tissue engineering approach for orbital bone repair based upon a Cyclic Acetal biomaterial formed from 5-ethyl-5-(hydroxymethyl)-β,β-dimethyl-1,3-dioxane-2-ethanol diacrylate (EHD) and poly(ethylene glycol) diacrylate (PEGDA). The EHD monomer and PEGDA polymer may be fabricated into an EH-PEG hydrogel by radical polymerization. The objectives of this work were to study (1) the tissue response to EH-PEG hydrogels in an orbital bone defect and (2) the induction of bone formation by delivery of bone morphogenetic protein-2 (BMP-2) from EH-PEG hydrogels. EH-PEG hydrogels were fabricated and implanted into an 8-mm rabbit orbital floor defect. Experimental groups included unloaded EH-PEG hydrogels, and EH-PEG hydrogels containing 0.25 μg and 2.5 μg BMP-2/implant. Results demonstrated that the unloaded hydrogel was initially bordered by a fibrin clot and then by fibrous encapsulation. BMP-2 loaded EH-PEG hydrogels, independent of concentration, were surrounded by fibroblasts at both time points. Histological analysis also demonstrated that significant bone growth was present at the 2.5 μg BMP-2/implant group at 28 days. This work demonstrates that the EH-PEG construct is a viable option for use and delivery of BMP-2 in vivo. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009
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Cyclic Acetal hydroxyapatite composites and endogenous osteogenic gene expression of rat marrow stromal cells
Journal of Tissue Engineering and Regenerative Medicine, 2009Co-Authors: Minal Patel, Thomas A Dunn, Sarah Tostanoski, J FisherAbstract:In this study, bone marrow stromal cells (BMSCs) were differentiated on Cyclic Acetal composites containing hydroxyapatite (HA) particles (110 or 550 nm). These composites were evaluated for their role in influencing osteogenic signalling by encapsulated BMSCs. While a number of factors exert influence on osteogenic signalling during the production of an osteogenic matrix, we hypothesize that HA particles may upregulate bone growth factor expression due to enhanced BMSC adhesion. To this end, fluorescence-activated cell sorting (FACS) analysis was performed for the evaluation of BMSC surface marker expression after culture on two-dimensional (2D) Cyclic Acetal/HA composites. Three-dimensional (3D) composites were then fabricated by incorporating 110 or 550 nm HA particles at 5, 10 and 50 ng/ml concentrations. Bone growth factor molecules (TGFbeta1, FGF-2 and PDGFa), bone biomarker molecules (ALP, OC, OPN and OCN) and extracellular matrix-related molecules (FN, MMP-13, Dmp1 and aggrecan) were selected for evaluation of osteogenic signalling mechanisms when in presence of these composites. FACS results at day 0 demonstrated that BMSCs were a heterogeneous population with a small percentage of cells staining positive for CD29, CD90 and CD51/61, while staining negative for CD34 and CD45. At day 3, a significant enrichment of cells staining strongly for CD29, CD90 and CD51/61 was achieved. Gene expression patterns for bone growth factors and extracellular matrix molecules were found to be largely dependent upon the size of HA particles. Bone marker molecules, except OCN, had unaltered expression patterns in response to the varied size of HA particles. Overall, the results indicate that larger-sized HA particles upregulate PDGF and these groups were also associated with the most significant increase in osteodifferentiation markers, particularly ALP. Our results suggest that endogenous signalling is dependent upon material properties. Furthermore, we propose that studying gene expression patterns induced by the surrounding biomaterials environment is a fundamental step in the creation of engineered tissues.
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synthesis and properties of Cyclic Acetal biomaterials
Journal of Biomedical Materials Research Part A, 2007Co-Authors: Jennifer L Moreau, Dafna Kesselman, J FisherAbstract:There is an increasing need to develop new biomaterials as tissue engineering scaffolds. Unfortunately, many of the materials that have been studied for these purposes are polyesters that hydrolytically degrade into acidic products, which may harm the surrounding tissue, and lead to accelerated degradation of the biomaterial. To overcome this disadvantage, a novel class of biomaterials based on a Cyclic Acetal unit has been created. Specifically, materials based upon the monomer 5-ethyl-5-(hydroxymethyl)-beta,beta-dimethyl-1,3-dioxane-2-ethanol diacrylate (EHD) is examined. This study investigates the effects of fabrication parameters, including initiator content, volume of diluent, and volume of accelerant, on several properties of EHD networks. Twelve different formulations were fabricated by varying the three parameters in a factorial design. The effects of the fabrication parameters on properties of the EHD networks were examined. Results show that the volume of accelerant most affected the EHD network gelation time, while the volume of diluent most affected the maximum reaction temperature, sol fraction, and degree of swelling. Cell viability on the EHD networks varied between (18 +/- 6)% and (57 +/- 10)% of the control at 4 h, and between (36 +/- 14)% and (140 +/- 50)% of the control at 8 h. These results indicate that it is possible to control the properties of the EHD networks by varying the fabrication parameters, and that EHD networks support a viable cell population.
