Self-Forming Norbornene-Tetrazine Hydrogels with Independently Tunable Properties |
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Authors: | Kirstene A Gultian Roshni Gandhi Tae Won B Kim Sebastián L Vega |
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Institution: | 1. Department of Biomedical Engineering, Rowan University, Glassboro, NJ, 08028 USA;2. Department of Orthopaedic Surgery, Cooper Medical School of Rowan University, Camden, NJ, 08103 USA |
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Abstract: | Although photopolymerization reactions are commonly used to form hydrogels, these strategies rely on light and may not be suitable for delivering therapeutics in a minimally invasive manner. Here, hyaluronic acid (HA) macromers are modified with norbornene (Nor) or tetrazine (Tet) and upon mixing click into covalently crosslinked Nor-Tet hydrogels via a Diels–Alder reaction. By incorporating a high degree of Nor and Tet substitution, Nor-Tet hydrogels with a broad range in elastic moduli (5 to 30 kPa) and fast gelation times (1 to 5 min) are achieved. By pre-coupling methacrylated HANor macromers with thiolated peptides via a Michael addition reaction, Nor-Tet hydrogels are peptide-functionalized without affecting their physical properties. Mesenchymal stem cells (MSCs) on RGD-functionalized Nor-Tet hydrogels adhere and exhibit stiffness-dependent differences in matrix mechanosensing. Fluid properties of Nor-Tet hydrogel solutions allow for injections through narrow syringe needles and can locally deliver viable cells and peptides. Substituting HA with enzymatically degradable gelatin also results in cell-responsive Nor-Tet hydrogels, and MSCs encapsulated in Nor-Tet hydrogels preferentially differentiate into adipocytes or osteoblasts, based on 3D cellular spreading regulated by stable (HA) and degradable (gelatin) macromers. |
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Keywords: | biochemical modifications gelatin hyaluronic acid injectable hydrogels matrix mechanosensing peptides |
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