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Synthesis and Characterization of a Thermoresponsive Hydrogel Scaffold for Bone Tissue Engineering Applications

Daneshvar, Anahita | 2025

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  1. Type of Document: Ph.D. Dissertation
  2. Language: Farsi
  3. Document No: 58295 (48)
  4. University: Sharif University of Technology
  5. Department: Institute for Nanoscience and Nanotechnology
  6. Advisor(s): Vossoughi, Manouchehr; Farokhi, Mehdi; Bonakdar, Shahin
  7. Abstract:
  8. Injectable hydrogels have emerged as promising candidates for bone tissue engineering due to their compatibility with minimally invasive procedures and ability to conform to irregular bone defects. In this study, a novel temperature-sensitive copolymer based on silk fibroin (PF-127-g-SF) was synthesized and its properties were evaluated. For this purpose, the hydroxyl groups of poloxamer were first modified to carboxylic acid groups (PF-127-COOH), and then grafted onto silk fibroin through a carbodiimide coupling reaction, thereby imparting thermosensitivity to the fibroin structure. The resulting copolymer exhibited a higher sol-gel transition temperature (34 °C at 16% w/v) compared to pure PF-127 (23 °C at 20% w/v), making it more suitable for injectable applications. While the pure PF-127 hydrogel gelled immediately upon reaching 37 °C, the PF-127-g-SF sample required approximately 3.5 minutes (218 ± 3 seconds) to gel. Upon incorporating hydroxyapatite nanoparticles at concentrations of 5%, 10%, and 20%, this gelation time was reduced to approximately 3.1 minutes (187 ± 5 seconds), 2.7 minutes (166 ± 8 seconds), and 2.3 minutes (138 ± 10 seconds), respectively. This reduction was attributed to the increased density of crosslinking points, leading to enhanced gel strength and functionality for clinical use. While pure PF-127 hydrogel degraded within 72 hours in an aqueous environment, the synthesized copolymer formed a stable network with a durability exceeding two weeks. The addition of nanoparticles further reduced pore size from 87 to 74 micrometers, decreased water uptake, controlled swelling and degradation rates, and extended hydrogel stability up to four weeks. Rheological analyses also demonstrated an increase in storage modulus and a shift in yield strain from less than 10% to around 30%, indicating improved mechanical strength and flexibility of the modified gel compared to pure PF-127. Incorporating mineral nanoparticles enhanced the mechanical properties of the hydrogel without significantly altering the phase transition temperature; however, at 20% concentration, the formation of aggregates and reduced gel integrity led to decreased compressive strength. Cellular studies using MG-63 cells further highlighted the need to optimize nanoparticle concentration to enhance cell viability and mineralization
  9. Keywords:
  10. Thermosensitive Hydrogels ; Silk Fibroin ; Nanohydroxyapatite Coathing ; Bone Regeneration ; Bone Tissue Engineering ; Poloxamer 127

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