Injectable in situ forming xylitol–PEG-based hydrogels for cell encapsulation and delivery

•Injectable poly(xylitol-co-maleate-co-PEG) (pXMP) macromers were synthesized.•pXMP hydrogels exhibited a broad range of compressive moduli.•Hydrogels displayed controlled degradability and preferential albumin adsorption.•Hydrogels exhibited exceptional cytocompatibility in vitro.•Hydrogels promoted cell adhesion and proliferation in 2D and 3D cell cultures in vitro. Injectable in situ crosslinking hydrogels offer unique advantages over conventional prefabricated hydrogel methodologies. Herein, we synthesize poly(xylitol-co-maleate-co-PEG) (pXMP) macromers and evaluate their performance as injectable cell carriers for tissue engineering applications. The designed pXMP elastomers were non-toxic and water-soluble with viscosity values permissible for subcutaneous injectable systems. pXMP-based hydrogels prepared via free radical polymerization with acrylic acid as crosslinker possessed high crosslink density and exhibited a broad range of compressive moduli that could match the natural mechanical environment of various native tissues. The hydrogels displayed controlled degradability and exhibited gradual increase in matrix porosity upon degradation. The hydrophobic hydrogel surfaces preferentially adsorbed albumin and promoted cell adhesion and growth in vitro. Actin staining on cells cultured on thin hydrogel films revealed subconfluent cell monolayers composed of strong, adherent cells. Furthermore, fabricated 3D pXMP cell–hydrogel constructs promoted cell survival and proliferation in vitro. Cumulatively, our results demonstrate that injectable xylitol–PEG-based hydrogels possess excellent physical characteristics and exhibit exceptional cytocompatibility in vitro. Consequently, they show great promise as injectable hydrogel systems for in situ tissue repair and regeneration.