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Development of Photocured Bioinks Based on GelMa and MXene for Muscle and Neural Tissue Engineering

Lotfi Ghameshlou, Roya | 2024

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  1. Type of Document: Ph.D. Dissertation
  2. Language: Farsi
  3. Document No: 58216 (48)
  4. University: Sharif University of Technology
  5. Department: Institute for Nanoscience and Nanotechnology
  6. Advisor(s): Simchi, Abdolreza; Purjavadi, Ali; Tamjid, Elnaz
  7. Abstract:
  8. Despite the promising potential of 3D bioprinting for personalized medicine, this technology is still under development and faces challenges, such as the lack of bioinks capable of precise printing while maintaining high cell viability. The physical and chemical properties of bioinks, including mechanical, rheological, and biological characteristics, play a key role in the success of printing targeted scaffolds. In this study, photo-crosslinkable Gelatin methacrylate (GelMa)-Ti3C2 MXene (MX) bioinks were developed for muscle and nerve tissue engineering. Two-dimensional MX phase was synthesized using an in-situ HF generation method. To prepare photo-crosslinkable hydrogels, type I (IG and LAP) and type II (EY) photo-initiators were used. It was found that the addition of MX phase impaired crosslinking during photopolymerization, thus affecting the thickness, porosity, swelling ratio, degradation, and mechanical properties of the hydrogels. While only composite hydrogel films with a thickness of 500 μm could be fabricated using IG and EY photo-initiators through 4–5 minutes of irradiation, centimeter-thick films were produced using LAP irradiated for 60 seconds. The highest electrical conductivity (1 mS•cm⁻¹) was observed for hydrogels containing LAP and 0.1 mg•mL⁻¹ MX, while the highest mechanical stiffness (68.3 ± 0.9 kPa) was achieved with IG at the same MX concentration. Biocompatibility studies showed that MX-containing hydrogels supported over 87% cell viability and proliferation of C2C12 and PC12 cells on the hydrogel surface, while encapsulated cells within the 3D hydrogel network exhibited viability exceeding 90%, indicating favorable cell growth and proliferation. Rheological analyses revealed that increasing MX concentration enhanced shear-thinning behavior under applied shear stress. The nanocomposite hydrogel was successfully used as a bioink in extrusion-based 3D printing, producing structures with a well-organized network at a pressure of 8–12 kPa and a printing speed of 2–3 mm•s⁻¹. 3D bioprinting of C2C12 cells with GelMa-MX (0.1) showed over 90% viability and a threefold increase in metabolic activity within 7 days. The presence of MX and its conductivity promoted cell differentiation and myotube formation. Electrical stimulation, combined with the electrical conductivity of the nanocomposite, enhanced cell differentiation, increased the number and size of myotubes, and upregulated MYOG and MYHC gene expression by 3–4 times. Successful cell differentiation within the printed GelMa-MX constructs was also observed under electrical stimulation. In vivo implantation of GelMa-MX nanocomposites in a mouse model for peripheral nerve injury (PNI) demonstrated significant improvement in sensory, motor, and sensorimotor function of the injured sciatic nerve. Electrophysiological and histological analyses affirmed the potential of GelMa-MX nanocomposite hydrogels for nerve regeneration in vivo
  9. Keywords:
  10. Three Dimentional Bioprinting ; Bioink ; MXene Fibers ; Peripheral Nerve Injury ; Methacrylate Gelatin ; Muscles

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