Self-Forming Norbornene-Tetrazine Hydrogels with Independently Tunable Properties.
Kirstene A GultianRoshni GandhiTae Won B KimSebastián L VegaPublished in: Macromolecular bioscience (2022)
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.
Keyphrases
- hyaluronic acid
- mesenchymal stem cells
- drug delivery
- tissue engineering
- minimally invasive
- umbilical cord
- wound healing
- extracellular matrix
- mental health
- stem cells
- cell therapy
- type diabetes
- oxidative stress
- physical activity
- cancer therapy
- high resolution
- induced apoptosis
- metabolic syndrome
- ultrasound guided
- bone marrow
- endoplasmic reticulum stress
- mass spectrometry
- cell proliferation