fabricating-degradable-thermoresponsive-hydrogels-on-multiple-length

Fabricating Degradable Thermoresponsive Hydrogels on Multiple Length Scales via Reactive Extrusion, Microfluidics, Self-assembly, and Electrospinning

While various smart materials have been explored for a variety of biomedical applications (e.g., drug delivery, tissue engineering, bioimaging, etc.), ...

McMaster University

Injectable hydrogels based on carboxymethyl cellulose and dextran, reinforced with rigid rod-like cellulose nanocrystals (CNCs) and aldehyde-functionalized CNCs (CHO-CNCs), were prepared and characterized. The mechanical properties, internal morphology, and swelling of injectable hydrogels with unmodified and modified CNCs at various loadings were examined. In all cases, gelation occurred within seconds as the hydrogel components were extruded from a double-barrel syringe, and the CNCs were evenly distributed throughout the composite, as observed by scanning and transmission electron microscopy. When immersed in purified water or 10 mM PBS, all CNC-reinforced hydrogels maintained their original shape for more than 60 days. The maximum storage modulus was observed in hydrogels with 0.250 wt % of unmodified CNCs and 0.375 wt % of CHO-CNCs. CHO-CNCs acted as both a filler and a chemical cross-linker, making the CHO-CNC-reinforced hydrogels more elastic, more dimensionally stable, and capable of facilitating higher nanoparticle loadings compared to hydrogels with unmodified CNCs, without sacrificing mechanical strength. No significant cytotoxicity to NIH 3T3 fibroblast cells was observed for the hydrogels or their individual components. These properties make CNC-reinforced injectable hydrogels of potential interest for various biomedical applications such as drug delivery vehicles or tissue engineering matrices. 

Injectable polysaccharide hydrogels reinforced with cellulose nanocrystals: morphology, rheology, degradation, and cytotoxicity.

Injectable PEG-analogue hydrogels based on poly(oligoethylene glycol methacrylate) have been developed based on complementary hydrazide and aldehyde reactive linear polymer precursors. These hydrogels display the desired biological properties of PEG, form covalent networks in situ following injection, and are easily modulated for improved control over their functionality and physiochemical properties. 

Injectable and tunable poly(ethylene glycol) analogue hydrogels based on poly(oligoethylene glycol methacrylate).

The potential of poly(oligoethylene glycol methacrylate) (POEGMA) hydrogels with varying thermosensitivities as soft materials for biomedical applications is demonstrated. Hydrogels are prepared from hydrazide and aldehyde functionalized POEGMA precursors, yielding POEGMA hydrogels with a volume phase transition temperature (VPTT) below (PO0), close to (PO10) and well above (PO100) physiological temperature. Hydrogels with VPTTs close to and above physiological temperature exhibit biological properties similar to those typically observed for poly(ethylene glycol) hydrogels (i.e. low protein adsorption, low cell adhesion and minimal inflammatory responses in vivo) while hydrogels with VPTTs lower than physiological temperature exhibit biological properties more analogous to poly(N-isopropylacrylamide) above its phase transition temperature (temperature-switchable cell adhesion, higher protein adsorption and somewhat more acute inflammation in vivo). As such, the use of POEGMA precursors with varying chain lengths of ethylene oxide grafts offers a versatile platform for the design of hydrogels with tunable physiological properties via simple copolymerization. 

Injectable poly(oligoethylene glycol methacrylate)-based hydrogels with tunable phase transition behaviours: physicochemical and biological responses.

A series of poly(ethylene glycol) (PEG) hydrogels was synthesized using strain-promoted alkyne-azide cycloaddition (SPAAC) between PEG chains terminated with either aza-dibenzocyclooctynes or azide functionalities. The gelation process was found to occur rapidly upon mixing the two components in aqueous solution without the need for external stimuli or catalysts, making the system a candidate for use as an injectable hydrogel. The mechanical and rheological properties of these hydrogels were found to be tunable by varying the polymer molecular weight and the number of cross-linking groups per chain. The gelation times of these hydrogels ranged from 10 to 60 s at room temperature. The mass-based swelling ratios varied from 45 to 76 at maximum swelling (relative to the dry state), while the weight percent of polymer in these hydrogels ranged from 1.31 to 2.05%, demonstrating the variations in amount of polymer required to maintain the structural integrity of the gel. Each hydrogel degraded at a different rate in PBS at pH = 7.4, with degradation times ranging from 1 to 35 days. By changing the composition of the two starting components, it was found that the Young's modulus of each hydrogel could be varied from 1 to 18 kPa. Hydrogel incubation with bovine serum albumin showed minimal protein adsorption. Finally, a cell cytotoxicity study of the precursor polymers with 3T3 fibroblasts demonstrated that the azide- and strained alkyne-functionalized PEGs are noncytotoxic. 

Article	Year
Injectable polysaccharide hydrogels reinforced with cellulose nanocrystals: morphology, rheology, degradation, and cytotoxicity. Biomacromolecules\| PubMed ID: 24206059	2013
Injectable and tunable poly(ethylene glycol) analogue hydrogels based on poly(oligoethylene glycol methacrylate). Chemical communications (Cambridge, England)\| PubMed ID: 24531402	2014
Injectable poly(oligoethylene glycol methacrylate)-based hydrogels with tunable phase transition behaviours: physicochemical and biological responses. Acta biomaterialia\| PubMed ID: 24911529	2014
Properties of Poly(ethylene glycol) Hydrogels Cross-Linked via Strain-Promoted Alkyne-Azide Cycloaddition (SPAAC). Biomacromolecules\| PubMed ID: 26842783	2016

Emilia Bakaic

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