Collagen organization deposited by fibroblasts encapsulated in pH responsive methacrylated alginate hydrogels

The pH of dermal wounds shifts from neutral during the inflammatory phase to slightly basic in the tissue remodeling phase. Stage specific wound treatment can be developed using environmentally responsive alginate hydrogels. The chemistry of these networks dictates swelling behavior. Here, we fabricated alginate hydrogels using chain growth, step growth, and combined mixed mode gelation methods to crosslink methacrylated alginate (ALGMA) and gain control over swelling responses. Methacrylation of the alginate network was confirmed through NMR spectroscopy. Strontium cations were introduced to fabricate stiffer, dually crosslinked hydrogels. Dual crosslinking significantly decreased the swelling response over the pH range of 3-9 for step growth and chain growth hydrogels, with no impact on mixed mode hydrogels. The extent of crosslinking altered the hydrogel degradation profiles under accelerated degradation conditions. Encapsulated NIH/3T3 fibroblasts in the different ALGMA hydrogels remained viable with greater cell proliferation in the stiffer gels. Collagen organization deposited by the NIH/3T3 fibroblasts was monitored using second harmonic generation (SHG) microscopy and was influenced by the crosslinking mechanism. Ionic chain growth and ionic mixed mode crosslinked ALGMA hydrogels caused relatively isotropic collagen organization, particularly 10 days post-cell encapsulation. Principal component analysis (PCA) was employed to uncover correlations between the observed properties. The ability of these environmentally responsive gels to induce isotropic collagen and respond to pH changes means they hold promise as phase specific wound dressings. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 2934-2943, 2018.