Strategies to encapsulate cells in cytocompatible 3-dimensional hydrogels with tunable mechanical properties and degradability without harmful gelling conditions are highly desired for regenerative medicine applications. Here we reported a method for preparing poly(ethylene glycol)-co-polycarbonate hydrogels through copper-free, strain-promoted azide-alkyne cycloaddition (SPAAC) “Click” chemistry. Hydrogels with varying mechanical properties were formed by “clicking” azido-functionalized poly(ethylene glycol)-co-polycarbonate macromers with dibenzocyclooctyne functionalized poly(ethylene glycol) under physiological conditions within minutes. Bone marrow stromal cells encapsulated in these gels exhibited higher cellular viability than those encapsulated in photo-crosslinked poly(ethylene glycol) dimethacrylate. The precise control over the macromer compositions, the cytocompatible SPAAC crosslinking, and the degradability of the polycarbonate segments combined make these hydrogels promising candidates for scaffold- and stem cell-assisted tissue repair and regeneration.

Despite the increasing demands for functional degradable biomaterials, strategies for generating materials with modular compositions and well-defined functionalities from common building blocks are still lacking. Here we report an azido-functionalized cyclic carbonate monomer, AzDXO, that exhibited controlled/"living" ring-opening polymerization kinetics under the catalysis of 1,8-diazabicyclo[5.4.0]-undec-7-ene. Homopolymerization of AzDXO and copolymerization of AzDXO with lactide resulted in polycarbonate and poly(ester-carbonates) with well-defined composition and narrow polydispersity. Further side-chain functionalizations of these polymers were accomplished under facile conditions via copper-catalyzed or copper-free strain-promoted azido-alkyne cyclcoaddition. This versatile monomer building block, obtainable in two steps without tedious purifications, provides a practical solution to the preparation of welldefined functional polycarbonates and poly(ester-carbonates).