Synthesis and characterization of hyaluronic acid–poly(ethylene glycol) hydrogels via Michael addition: An injectable biomaterial for cartilage repair

Jin, Rong; Teixeira, Liliana S. Moreira; Krouwels, Anita; Dijkstra, Pieter J.; Blitterswijk, Clemens A. van; Karperien, Marcel; Feijén, Jan

doi:10.1016/j.actbio.2009.12.024

Cited by 277 publications

(210 citation statements)

References 45 publications

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“…The average percentage of thiol substitution (approximately 10%) was determined by Ellman's test. This percentage of substitution is in agreement with values in the literature since it is considered that a partial modification (10-20%) is desirable to achieve polyplexes with well-defined sizes [10]. CSHA5N, 2-CSHA5H, 3-CSHA7N, 4-CSHA7H The presence of two equivalence points in the potentiometric titration curve of HASSNH 2 further confirmed the success of the modification reaction and indicated the pH range more adequate for polyplex preparation.…”

Section: Ha Was Successfully Modified With Cystaminesupporting

confidence: 76%

“…1 [10][11][12]. Briefly, 500 mg of hyaluronic acid was dissolved in 100 ml of distilled H 2 O, a one and a half molar excess (relative to the carboxylic acid groups in HA) of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDAC, 0.378 g, 1.974 mmol), and three molar excess of cystamine (0.889 g, 3.947 mmol) were added to the solution.…”

Section: Modification Of Hyaluronic Acid With Cystamine (Hassnh 2 )mentioning

confidence: 99%

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Evaluation of cystamine-modified hyaluronic acid/chitosan polyplex as retinal gene vector

Oliveira

Marcelo

Costa

et al. 2016

Materials Science and Engineering: C

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Purpose: A successful gene therapy approach can prevent or treat congenital and acquired diseases. However, there is still no ideal non-viral vector for gene delivery in a safe and timely manner. In this report the anionic polymer hyaluronic acid (HA) was investigated as a potential vector for gene therapy. Due to its intrinsic characteristics it constitutes an excellent candidate to deliver therapeutic genes, pending the modification of its surface charge. Methods: To modify its charge, HA was modified with cystamine. Several formulations were prepared using modified HA combined with sodium sulfate, sodium triphosphate, K-carrageenan and chitosan. Vectors were characterized with respect to size, charge, DNA load and its protection, and effect on cell viability. The better performing formulations were further evaluated in vitro for their transfection efficiency in HEK293T and ARPE-19 cells. Results: Cell viability assays showed low cytotoxicity for both polymers. Gene transfer efficiency depended on cell line and formulation, but no increased transfection efficiency was observed with the modified polymer. Conclusions: HA has great potential as a gene therapy vector, but further optimization, including incorporation of a higher percentage of positive groups in HA, is needed before its use as a gene delivery vector.

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Section: Ha Was Successfully Modified With Cystaminesupporting

confidence: 76%

Section: Modification Of Hyaluronic Acid With Cystamine (Hassnh 2 )mentioning

confidence: 99%

Evaluation of cystamine-modified hyaluronic acid/chitosan polyplex as retinal gene vector

Oliveira

Marcelo

Costa

et al. 2016

Materials Science and Engineering: C

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“…The actual synthetic introduction of ''new'' or additional reduced sulfhydryl groups at the e-amine of lysine amino acid residues is possible with reactions that utilize 2-iminothiolane (2-IT), 2,6,26,30,114 mercaptosuccinimide, 115 or N-succinimidyl-S-acetylthioacetate (SATA). 7,114,116 Alternatively, carboxyl groups on molecules like heparin and hyaluronic acid can be thiolated with 3,3¢dithiobis(propanoic)-hydrazide 113,117 or divinylsulfone, 92,118 for hydroxyl groups of molecules with a cholesterol-like core. 119 In the application of DTPH the integral disulfide bond is subsequently reduced with DTT reagent.…”

Section: Synthetic Chemistry Reactions For Covalent Epirubicin-(c 3 -mentioning

confidence: 99%

“…141 Contributions of ADCC and complement-mediated cytolysis to the in vivo cytotoxic anti-neoplastic potency of covalent anthracycline immunochemotherapeutics would be further complemented by, and directly correlate with the additive and synergistic levels of anti-neoplastic potency produced by anti-trophic receptor monoclonal immunoglobulin applied in dual combination with nonconjugated chemotherapeutic agents. [48][49][50][53][54][55][56][57][58][59]113,118 Additive or synergistic interactions of this type have been detected with anti-HER2/neu in concert with cyclophosphamide, 48,49 docetaxel, 48 doxorubicin, 48,49 etoposide, 48 methotrexate, 48 paclitaxel, 48,49 or vinblastine. 48 Fifth, several modifications could have been made in the synthesis strategy in order to increase the anthracycline molar-incorporation index.…”

Section: Cytotoxic Anti-neoplastic Potencymentioning

confidence: 99%

Synthesis of a Covalent Epirubicin-(C₃-amide)-Anti-HER2/neuImmunochemotherapeutic Utilizing a UV-Photoactivated Anthracycline Intermediate

Coyne

Jones²,

Bear³

2012

Cancer Biotherapy and Radiopharmaceuticals

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The C 3 -monoamine on the carbohydrate moiety (daunosamine -NH 2 -3¢) of epirubicin was reacted under anhydrous conditions with succinimidyl 4,4-azipentanoate to create a covalent UV-photoactivated epirubicin-(C 3 -amide) intermediate with primary amine-reactive properties. A synthetic covalent bond between the UV-photoactivated epirubicin-(C 3 -amide) intermediate and the e-amine of lysine residues within the amino acid sequence of anti-HER2/neu monoclonal immunoglobulin was subsequently created by exposure to UV light (354 nm) for 15 minutes. Size-separation by sodium dodecyl sulfate-polyacrylamide gel electrophoresis combined with immunodetection analysis and chemiluminescent autoradiographic imaging revealed a lack of IgG-IgG polymerization or degradative protein fragmentation of the covalent epirubicin-(C 3 -amide)-[anti-HER2/neu] immunochemotherapeutic. Retained binding-avidity of epirubicin-(C 3 -amide)-[anti-HER2/neu] was validated by cell-ELISA utilizing monolayer populations of chemotherapeutic-resistant mammary adenocarcinoma SKBr-3 which highly overexpress membrane-associated HER2/neu complexes. Between epirubicin-equivalent concentrations of 10 -10 to 10 -6 M the covalent epirubicin-(C 3 -amide)-[anti-HER2/neu] immunochemotherapeutic consistently evoked levels of cytotoxic anti-neoplastic potency that were highly analogous to chemotherapeuticequivalent concentrations of epirubicin. Cytotoxic anti-neoplastic potency of epirubicin-(C 3 -amide)-[anti-HER2/ neu] against chemotherapeutic-resistant mammary adenocarcinoma SKBr-3 challenged with epirubicin-(C 3 -amide)-[anti-HER2/neu] at an epirubicin-equivalent concentration of 10 -6 M was 88.5% (e.g., 11.5% residual survival). Between final epirubicin-equivalent concentrations of 10 -8 and 10 -7 M there was a marked threshold increase in the mean cytotoxic anti-neoplastic activity for epirubicin-(C 3 -amide)-[anti-HER2/neu] from 9.9% to 66.9% (90.2% to 33.1% residual survival).

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“…39 It can only interfere with the rarely occurring amino acid cystein, 40 which, however, is also a problem of the strain-promoted azide−alkyne cycloaddition. 41 In addition, the thiol-Michael addition only requires substrate syntheses with a low number of steps that each have high yield, and the applicability of the thiol-Michael addition for in situ cell encapsulation has been demonstrated by Hubbell and coworkers 42 and Feijen and co-workers, 43 who proved it to be harmless to cells. Nevertheless, this chemistry has not to date been combined with droplet-microfluidic particle templating to produce monodisperse, cell-laden microgels.…”

Section: ■ Introductionmentioning

confidence: 99%

Controlled Synthesis of Cell-Laden Microgels by Radical-Free Gelation in Droplet Microfluidics

et al. 2012

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Micrometer-sized hydrogel particles that contain living cells can be fabricated with exquisite control through the use of dropletbased microfluidics and bioinert polymers such as polyethyleneglycol (PEG) and hyperbranched polyglycerol (hPG). However, in existing techniques, the microgel gelation is often achieved through harmful reactions with free radicals. This is detrimental for the viability of the encapsulated cells. To overcome this limitation, we present a technique that combines droplet microfluidic templating with bio-orthogonal thiol−ene click reactions to fabricate monodisperse, cell-laden microgel particles. The gelation of these microgels is achieved via the nucleophilic Michael addition of dithiolated PEG macro-cross-linkers to acrylated hPG building blocks and does not require any initiator. We systematically vary the microgel properties through the use of PEG linkers with different molecular weights along with different concentrations of macromonomers to investigate the influence of these parameters on the viability and proliferation of encapsulated yeast cells. We also demonstrate the encapsulation of mammalian cells including fibroblasts and lymphoblasts.

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Synthesis and characterization of hyaluronic acid–poly(ethylene glycol) hydrogels via Michael addition: An injectable biomaterial for cartilage repair

Cited by 277 publications

References 45 publications

Evaluation of cystamine-modified hyaluronic acid/chitosan polyplex as retinal gene vector

Evaluation of cystamine-modified hyaluronic acid/chitosan polyplex as retinal gene vector

Synthesis of a Covalent Epirubicin-(C₃-amide)-Anti-HER2/neuImmunochemotherapeutic Utilizing a UV-Photoactivated Anthracycline Intermediate

Controlled Synthesis of Cell-Laden Microgels by Radical-Free Gelation in Droplet Microfluidics

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Synthesis and characterization of hyaluronic acid–poly(ethylene glycol) hydrogels via Michael addition: An injectable biomaterial for cartilage repair

Cited by 277 publications

References 45 publications

Evaluation of cystamine-modified hyaluronic acid/chitosan polyplex as retinal gene vector

Evaluation of cystamine-modified hyaluronic acid/chitosan polyplex as retinal gene vector

Synthesis of a Covalent Epirubicin-(C3-amide)-Anti-HER2/neuImmunochemotherapeutic Utilizing a UV-Photoactivated Anthracycline Intermediate

Controlled Synthesis of Cell-Laden Microgels by Radical-Free Gelation in Droplet Microfluidics

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Synthesis of a Covalent Epirubicin-(C₃-amide)-Anti-HER2/neuImmunochemotherapeutic Utilizing a UV-Photoactivated Anthracycline Intermediate