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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The effects of processing variables on electrospun poly(ethylene glycol) fibrous hydrogels formed from the thiol‐norbornene click reaction
Electrospinning has been used to create scaffolds with tunable micro/nano architecture, stiffness, and porosity to mimic native extracellular matrix. This study investigated the effects of electrospinning parameters and hydrogel formulation (solvent and crosslinker type) on the architecture and properties of fibrous poly(ethylene glycol) (PEG) hydrogels formed from a photoclick thiol‐norbornene reaction. Fibrous hydrogels were prepared using hydrogel precursors (four‐arm PEG norbornene and multi‐thiol crosslinker), sacrificial poly(ethylene oxide) (PEO, 400 kDa), and photoinitiator (I2959) in either 2,2‐triflouroethanol (TFE) or water. Three thiol crosslinkers‐ 2,2′‐(ethylenedioxy)diethanethiol (EDT), pentaerythritol tetrakis(3mercaptopropionate) (PTMP), and PEG dithiol (PEGDT)‐ were investigated. Fibrous PEG networks with uniform fibers were produced at applied voltages of 10 or 12 kV for TFE and 16 kV for water. Fiber diameters of electrospun hydrogels were largely affected by the solvent when combined with PEO concentration and ranged from 0.5 to 3.5 mm in dry state. While the effect of crosslinker type on fiber diameter, morphology, and porosity of the fibrous hydrogel was minimal, it did modulate its shear modulus. To this end, this study provides the groundwork for selecting processing parameters to achieve desired properties of fibrous PEG thiol‐norbornene hydrogels for intended tissue engineering applications ranging from neural, cardiovascular to musculoskeletal.
more » « less- Award ID(s):
- 1825692
- NSF-PAR ID:
- 10449891
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Journal of Applied Polymer Science
- Volume:
- 138
- Issue:
- 32
- ISSN:
- 0021-8995
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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