4 research outputs found
II Rosso e le stampe
Injectable, in situ-gelling magnetic
composite materials have been
fabricated by using aldehyde-functionalized dextran to cross-link
superparamagnetic nanoparticles surface-functionalized with hydrazide-functionalized
polyÂ(<i>N</i>-isopropylacrylamide) (pNIPAM). The resulting
composites exhibit high water contents (82–88 wt.%) while also
displaying significantly higher elasticities (G′ >60 kPa)
than
other injectable hydrogels previously reported. The composites hydrolytically
degrade via slow hydrolysis of the hydrazone cross-link at physiological
temperature and pH into degradation products that show no significant
cytotoxicity. Subcutaneous injections indicate only minor chronic
inflammation associated with material degradation, with no fibrous
capsule formation evident. Drug release experiments indicate the potential
of these materials to facilitate pulsatile, “on-demand”
changes in drug release upon the application of an external oscillating
magnetic field. The injectable but high-strength and externally triggerable
nature of these materials, coupled with their biological degradability
and inertness, suggest potential biological applications in tissue
engineering and drug delivery
Injectable, Mixed Natural-Synthetic Polymer Hydrogels with Modular Properties
A series of synthetic oligomers (based on the thermosensitive
polymer
polyÂ(<i>N</i>-isopropylacrylamide) and carbohydrate polymers
(including hyaluronic acid, carboxymethyl cellulose, dextran, and
methylcellulose) were functionalized with hydrazide or aldehyde functional
groups and mixed using a double-barreled syringe to create in situ
gelling, hydrazone-cross-linked hydrogels. By mixing different numbers
and ratios of different reactive oligomer or polymer precursors, covalently
cross-linked hydrogel networks comprised of different polymeric components
are produced by simple mixing of reactive components, without the
need for any intermediate chemistries (e.g., grafting). In this way,
hydrogels with defined swelling, degradation, phase transition, drug
binding, and mechanical properties can be produced with properties
intermediate to those of the mixture of reactive precursor polymers
selected. When this modular mixing approach is used, one property
can (in many cases) be selectively modified while keeping other properties
constant, providing a highly adaptable method of engineering injectable,
rapidly gelling hydrogels for potential in vivo applications
Injectable, Degradable Thermoresponsive Poly(<i>N</i>-isopropylacrylamide) Hydrogels
Degradable, covalently in situ gelling analogues of thermoresponsive
polyÂ(<i>N</i>-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
Tuning Gelation Time and Morphology of Injectable Hydrogels Using Ketone–Hydrazide Cross-Linking
Injectable,
covalently <i>in situ</i> forming hydrogels based on polyÂ(<i>N</i>-isopropylacrylamide) have been designed on the basis of
mixing hydrazide-functionalized nucleophilic precursor polymers with
electrophilic precursor polymers functionalized with a combination
of ketone (slow reacting) and aldehyde (fast reacting) functional
groups. By tuning the ratio of aldehyde:ketone functional groups as
well as the total number of ketone groups in the electrophilic precursor
polymer, largely independent control over hydrogel properties including
gelation time (from seconds to hours), degradation kinetics (from
hours to months), optical transmission (from 1 to 85%), and mechanics
(over nearly 1 order of magnitude) can be achieved. In addition, ketone-functionalized
precursor polymers exhibit improved cytocompatibility at even extremely
high concentrations relative to polymers functionalized with aldehyde
groups, even at 4-fold higher functional group densities. Overall,
increasing the ketone content of the precursor copolymers can result
in <i>in situ-</i>gellable hydrogels with improved transparency
and biocompatibility and equivalent mechanics and stimuli-responsiveness
while only modestly sacrificing the speed of gel formation