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Click chemistry reactions have become an important tool for synthesizing user-defined hydrogels consisting of poly(ethylene glycol) (PEG) and bioactive peptides for tissue engineering. However, because click crosslinking proceeds via a step-growth mechanism, multi-arm telechelic precursors are required, which has some disadvantages. Here, we report for the first time that this requirement can be circumvented to create PEG–peptide hydrogels solely from linear precursors through the use of two orthogonal click reactions, the thiol–maleimide Michael addition and thiol–norbornene click reaction. The rapid kinetics of both click reactions allowed for quick formation of norbornene-functionalized PEG–peptide block copolymers via Michael addition, which were subsequently photocrosslinked into hydrogels with a dithiol linker. Characterization and in vitro testing demonstrated that the hydrogels have highly tunable physicochemical properties and excellent cytocompatibility. In addition, stoichiometric control over the crosslinking reaction can be leveraged to leave unreacted norbornene groups in the hydrogel for subsequent hydrogel functionalization via bioorthogonal inverse-electron demand Diels–Alder click reactions with s -tetrazines. After selectively capping norbornene groups in a user-defined region with cysteine, this feature was leveraged for protein patterning. Collectively, these results demonstrate that our novel chemical strategy is a simple and versatile approach to the development of hydrogels for tissue engineering that could be useful for a variety of applications.
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Photochemical Control of Network Topology in PEG Hydrogels
Abstract Hydrogels are often synthesized through photoinitiated step‐, chain‐, and mixed‐mode polymerizations, generating diverse network topologies and resultant material properties that depend on the underlying network connectivity. While many photocrosslinking reactions are available, few afford controllable connectivity of the hydrogel network. Herein, a versatile photochemical strategy is introduced for tuning the structure of poly(ethylene glycol) (PEG) hydrogels using macromolecular monomers functionalized with maleimide and styrene moieties. Hydrogels are prepared along a gradient of topologies by varying the ratio of step‐growth (maleimide dimerization) to chain‐growth (maleimide‐styrene alternating copolymerization) network‐forming reactions. The initial PEG content and final network physical properties (e.g., modulus, swelling, diffusivity) are tailored in an independent manner, highlighting configurable gel mechanics and reactivity. These photochemical reactions allow high‐fidelity photopatterning and 3D printing and are compatible with 2D and 3D cell culture. Ultimately, this photopolymer chemistry allows facile control over network connectivity to achieve adjustable material properties for broad applications.
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- Award ID(s):
- 2348856
- PAR ID:
- 10582234
- Publisher / Repository:
- Wiley-VCH
- Date Published:
- Journal Name:
- Advanced Materials
- Volume:
- 36
- Issue:
- 46
- ISSN:
- 0935-9648
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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