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Development of a Brain Extracellular Matrix-Based Hydrogel with Drug Delivery Capability for Application in the Central Nervous System

Darbandi, Saba | 2025

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  1. Type of Document: M.Sc. Thesis
  2. Language: Farsi
  3. Document No: 58533 (06)
  4. University: Sharif University of Technology
  5. Department: Chemical and Petroleum Engineering
  6. Advisor(s): Mashayekhan, Shohreh
  7. Abstract:
  8. Following spinal cord injury (SCI), disruption of the blood–spinal cord barrier, along with inflammation and neuronal damage, leads to disconnection between neurons and a cascade of secondary and long-term complications that severely affect the patient's quality of life. Modern therapeutic strategies for SCI focus on repairing and restoring spinal cord function, with the use of biomaterials being one of the promising approaches. Among these, decellularized extracellular matrix (dECM), particularly of brain origin, provides a natural niche for neural cells and contributes to reduced inflammation, accelerated tissue regeneration, neural repair, and improved nervous system function. In this study, a bioreactor was used for the decellularization process. Compared to conventional methods, the bioreactor was more effective in removing cellular content while preserving the tissue structure. However, dECM alone lacks sufficient mechanical strength. Its combination with collagen enhances mechanical properties and has a high potential for nerve repair and regeneration. To further improve therapeutic performance, targeted drug delivery to the injury site was employed. Curcumin was selected as the therapeutic agent due to its anti-inflammatory, tissue-protective, and regenerative properties. However, its poor water solubility, low absorption, and rapid metabolism limit its pharmaceutical efficacy. To address these challenges, curcumin was complexed with β-cyclodextrin—a cyclic molecule with a hydrophobic cavity and hydrophilic exterior—resulting in enhanced solubility and a drug release rate of up to eighty percent. The optimal non-cytotoxic concentration of ten micromolars of curcumin was determined using cell viability assays. Results showed that the drug-releasing hydrogel preserved neuronal cell viability under oxidative stress and reduced reactive oxygen species (ROS) levels. Upon ROS exposure, cell viability in the drug-free hydrogel dropped to fifty-two percent, while in the drug-loaded hydrogel, it increased to seventy-eight percent. ROS levels in the drug-treated group were reduced by a quarter compared to the untreated group. These findings indicate that the designed hydrogel system holds significant potential for application in spinal cord injury repair
  9. Keywords:
  10. Collagen ; Drug Delivery ; Curcumin ; Beta-Cyclodextrin ; Nerve Tissue Engineering ; Extracellular Matrix ; Brain-Derived Decellularized Extracellular Matrix

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