Injectable, Mixed Natural-Synthetic Polymer Hydrogels with Modular Properties
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abstract
A series of synthetic oligomers (based on the thermosensitive polymer poly(N-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.