Self-healing hydrogels for cardiac tissue engineering

Date

2025-3-06

Author

Güner, Mustafa Bahadır

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This research developed an injectable, self-healing, and conductive composite hydrogel (HAGOE) for cardiac repair by integrating hyaluronic acid (HA)-based hydrogels, graphene oxide (GO), and exosomes isolated from hAMSCs conditioned in low-glucose environment. Three HA variants (40, 80, and 100 kDa) were functionalized with phenylboronic acid (PBA) or fructosamine via EDC coupling, with successful conjugation confirmed by NMR and FTIR. All hydrogels (10% w/v in PBS, 1:1 ratio) exhibited rapid gelation at physiological pH and maintained injectability. Degradation studies over 21 days revealed mass losses of 26% for HA40 versus 14% for HA80 and HA100, with preserved tensile strength despite reduced stiffness. Biological evaluation demonstrated enhanced cardiomyogenic and angiogenic differentiation, leading to the selection of HA80 for its optimal degradation-porosity balance. GO was synthesized from graphite and characterized by FTIR, Raman, XRD, and XPS, confirming single-layer structure (270 nm average size) and increased sp²-hybridized domains critical for conductivity. Dose-dependent testing (0.5–2.5 mg/mL) showed improved conductivity without altering mechanical properties or viability. While GO-5 and GO-15 (5 and 15 μg/cm²) enhanced both cardiomyogenic and angiogenic differentiation. Exosomes isolated from hAMSCs conditioned in low- or high-glucose media were non-cytotoxic and equally promoted cardiomyogenesis. However, low-glucose exosomes significantly augmented angiogenesis, justifying their inclusion in HAGOE. In a Sprague-Dawley rat MI model, HAGOE (HA80 + GO-5 + low-glucose exosomes) injection reduced fibrosis and reparative cardiac remodeling compared to saline. These results highlight HAGOE’s multifunctional potential as a therapeutic platform for infarct regeneration.

Subject Keywords

Self-Healing, Myocardial Infarction, Graphene Oxide, Exosome

URI

https://hdl.handle.net/11511/114551

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Graduate School of Natural and Applied Sciences, Thesis