Hydrazone-based hydrogel hydrolytically degradable in acidic environment

Vetrík, Miroslav; Přádný, Martin; Hrubý, Martin; Michálek, Jiřı́

doi:10.1016/j.polymdegradstab.2011.02.020

Cited by 17 publications

(18 citation statements)

References 15 publications

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“…Crosslinking of polyaldehyde derivative of hyaluronan by adipic acid dihydrazide is typical example of such method. Crosslinking reaction is based on the condensation of hydrazide and carbonyl group which proceeds under mild conditions (pH 6) and forms hydrolytically stable hydrazone bond which stable under physiological conditions (pH 7–8) (Figure d). Polyaldehyde derivative of hyaluronan could be prepared e.g.…”

Section: Chemistry Of Ha Its Modifications Its Use In Biomedical Inmentioning

confidence: 99%

Hyaluronic Acid and Its Derivatives in Coating and Delivery Systems: Applications in Tissue Engineering, Regenerative Medicine and Immunomodulation

Knopf‐Marques

Pravda

Wolfová

et al. 2016

Adv Healthcare Materials

193

159

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epithelial, connective, and nerve tissues of vertebrates. It is designated as a glycosaminoglycan. [1] Glycosaminoglycans are composed of disaccharide blocks of N-acetylgalactosamine or N-acetylglucosamine, (amino sugars) and uronic sugars such as glucuronic acid, iduronic acid or galactose. This group of heteropolysaccharides comprises HA, chondroitin sulfates, dermatan sulfate, heparin and heparin sulfates whose sulfation degree is less than that of heparin. Unlike other glycosaminoglycans, hyaluronan is not sulfated and it is self-standing, i.e. without an association with a core protein. [2] It was isolated in 1934 by Meyer and Palmer from bovine vitreous humor. [3] The polymer chain of hyaluronan comprises repeating disaccharide units where the pyranose rings are connected by β-1,3 bonds. The repeating units are bonded with a β-1,4 glycosidic bond within the chain between N-acetyl-D-glucosamine and D-glucuronic acid. At physiological pH each glucuronate unit, associated with its carboxylate group, carries an anionic charge. The hundreds of negative charges are fixed to each chain. These anionic groups are balanced with mobile cations such as Na + , K + , Ca 2+ and Mg 2+ . During ionization of D-glucuronic acid with the carboxylic groups, the charges influence the organization of the chains and their interactions with their surroundings. In turn, they are affected by pH and ionic strength. The chain organization and charge directly affect the solubility in water, since hyaluronan is water-insoluble when convertedAs an Extracellular Matrix (ECM) component, Hyaluronic acid (HA) plays a multi-faceted role in cell migration, proliferation and differentiation at micro level and system level events such as tissue water homeostasis. Among its biological functions, it is known to interact with cytokines and contribute to their retention in ECM microenvironment. In addition to its biological functions, it has advantageous physical properties which result in the industrial endeavors in the synthesis and extraction of HA for variety of applications ranging from medical to cosmetic. Recently, HA and its derivatives have been the focus of active research for applications in biomedical device coatings, drug delivery systems and in the form of scaffolds or cell-laden hydrogels for tissue engineering. A specific reason for the increase in use of HA based structures is their immunomodulatory and regeneration inducing capacities. In this context, this article reviews recent literature on modulation of the implantable biomaterial microenvironment by systems based on HA and its derivatives, particularly hydrogels and microscale coatings that are able to deliver cytokines in order to reduce the adverse immune reactions and promote tissue healing.

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Section: Chemistry Of Ha Its Modifications Its Use In Biomedical Inmentioning

confidence: 99%

Hyaluronic Acid and Its Derivatives in Coating and Delivery Systems: Applications in Tissue Engineering, Regenerative Medicine and Immunomodulation

Knopf‐Marques

Pravda

Wolfová

et al. 2016

Adv Healthcare Materials

193

159

View full text Add to dashboard Cite

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“…In addition, the hydrolytic lability of the hydrazone bond facilitates the fabrication of hydrogels capable of degrading over time in aqueous environments to a degree that depends on the cross-link density of the hydrogel network and the pH of the surrounding environment. [ 167,168 ] The decreased electrophilicity of the sp 2 carbon attached to nitrogen over that of a carbonyl group renders the hydrazone bond less reactive than its parent carbonyl, offering prolonged residence time within the body often on the timescale of several months. In addition, again owing in part to the high driving force for cross-link formation using this chemistry, hydrazonecross-linked hydrogels can exhibit relatively stronger mechanical properties to hydrogels prepared using other chemistries.…”

Section: Cross-linking Via Hydrazone Bond Formationmentioning

confidence: 99%

Designing Injectable, Covalently Cross‐Linked Hydrogels for Biomedical Applications

Patenaude

Smeets

Hoare

2014

Macromol. Rapid Commun.

165

125

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Hydrogels that can form spontaneously via covalent bond formation upon injection in vivo have recently attracted significant attention for their potential to address a variety of biomedical challenges. This review discusses the design rules for the effective engineering of such materials, and the major chemistries used to form injectable, in situ gelling hydrogels in the context of these design guidelines are outlined (with examples). Directions for future research in the area are addressed, noting the outstanding challenges associated with the use of this class of hydrogels in vivo.

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“…24 Extrapolation of the measured kinetics using a power law correlation that fits the data predicts a gel lifetime of several months at physiological pH (pH = 7.4), consistent with previously reported hydrolytic lifetimes of hydrazone cross-links. 25 GPC analysis of degradation products demonstrates that the gels degrade back to precursor copolymers (see Supporting Information, Figure S1-B). Note that the maximum water content (measured gravimetrically) upon thermal cycling decreases (albeit slightly) upon multiple cycles (p = 0.048, Figure 2), indicating a loss of hydrogel mass as a function of time that may be related to slow degradation of the hydrogel in the PBS media used for release studies.…”

Section: Acs Macro Lettersmentioning

confidence: 99%

Injectable, Degradable Thermoresponsive Poly(N-isopropylacrylamide) Hydrogels

2012

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Degradable, covalently in situ gelling analogues of thermoresponsive poly(N-isopropylacrylamide) (PNIPAM) hydrogels have been designed by mixing aldehyde and hydrazide-functionalized PNIPAM oligomers with molecular weights below the renal cutoff. Co-extrusion of the reactive polymer solutions through a double-barreled syringe facilitates rapid gel formation within seconds. The resulting hydrazone cross-links hydrolytically degrade over several weeks into low molecular weight oligomers. The characteristic reversible thermoresponsive swelling−deswelling phase transition of PNIPAM hydrogels is demonstrated. Furthermore, both in vitro and in vivo toxicity assays indicated that the hydrogel as well as the precursor polymers/degradation products were nontoxic at biomedically relevant concentrations. This chemistry may thus represent a general approach for preparing covalently cross-linked, synthetic polymer hydrogels that are both injectable and degradable.T hermoresponsive hydrogels based on poly(N-isopropylacrylamide) (PNIPAM) that switch from a hydrated, expanded state at low temperature to a collapsed state at high temperature have been extensively investigated in the literature. The proximity of the ∼32°C volume phase transition temperature (VPTT) of PNIPAM hydrogels with physiological temperature (37°C) has sparked particular interest in the biomedical applications of these hydrogels as "smart", environmentally tunable drug delivery vehicles, 1 tissue engineering scaffolds, 2 cell growth/separation supports, 3 and biomolecule separation and recovery matrices, 4 among other applications. 5 Despite their significant potential in biomedical applications, PNIPAM hydrogels have not achieved clinical success, primarily due to concerns regarding the ultimate fate of PNIPAM inside the body. Though toxic in its monomeric form, 5 poly(N-isopropylacrylamide) has been shown to be effectively noncytotoxic at concentrations realistic to many medical applications. 6 However, possible depolymerization and/or chronic bioaccumulation of PNIPAM represent significant regulatory barriers to medical use. An additional practical barrier is the need to fabricate current PNIPAM hydrogel formulations outside of the body, as the free radical chemistry and thermal or UV initiation 3 required to form the hydrogels can induce significant cell toxicity and cannot be performed in deep tissues. While weakly cross-linked hydrogels may be sufficiently viscous to facilitate injection, 4 injection of more highly elastic hydrogels is impractical. As a result, there is a need for mechanically robust PNIPAM-based hydrogels that can be introduced into the body through minimally invasive means and subsequently degrade into safe and clearable products.While many studies have explored the formation of injectable and degradable thermoresponsive hydrogels via physical association 1,7,8 or space-filling, 9 relatively few studies have addressed the challenge of creating injectable and degradable covalently cross-linked PNIPAM hydrogels. Hydrolytically degradab...

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Hydrazone-based hydrogel hydrolytically degradable in acidic environment

Cited by 17 publications

References 15 publications

Hyaluronic Acid and Its Derivatives in Coating and Delivery Systems: Applications in Tissue Engineering, Regenerative Medicine and Immunomodulation

Hyaluronic Acid and Its Derivatives in Coating and Delivery Systems: Applications in Tissue Engineering, Regenerative Medicine and Immunomodulation

Designing Injectable, Covalently Cross‐Linked Hydrogels for Biomedical Applications

Injectable, Degradable Thermoresponsive Poly(N-isopropylacrylamide) Hydrogels

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