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Fabrication of a Bioactive Scaffold Containing Alendronate for Regeneration of Osteoporotic Bone Defects

Alizadeh, Maryam | 2025

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  1. Type of Document: Ph.D. Dissertation
  2. Language: Farsi
  3. Document No: 58340 (06)
  4. University: Sharif University of Technology
  5. Department: Chemical and Petroleum Engineering
  6. Advisor(s): Abdekhodaie, Mohammad Jafar
  7. Abstract:
  8. The growing global demographic and the growing rate of osteoporosis provide the definitive rationale for the development of effective methods for the treatment of osteoporotic defects of bone. These methods should not only compensate for ongoing injuries but should also manipulate the inherent disease processes to enhance the effectiveness of treatment. Therefore, the present study attempts to develop bioactive nanocomposite hydrogels through two different modalities—microgels and injectable bulk hydrogels—for the purpose of delivering alendronate (ALN) as a treatment approach for osteoporotic fractures. During the first phase of the research, gelatin-containing nanocomposite microgels loaded with nanohydroxyapatite (nHAp) and ALN were prepared as cell carriers through an extrusion-based process. The effect of the incorporation of nHAp and nHAp-ALN on the physicochemical and biological properties of the microgels was evaluated for three different experimental groups: gelatin (pure) microgels (G), gelatin-nHAp-containing microgels (GH), and gelatin-nHAp-containing microgels loaded with nHAp-ALN (GHA). The diameter of the microgels was measured in the range of 190 to 320 μm for all three groups. ALN significantly increased the proliferation of human adipose-derived stem cells (hASCs) cultured on GHA microgels compared to the G and GH groups. Additionally, alkaline phosphatase (ALP) activity and Alizarin red staining demonstrated the enhancing effects of nHAp and ALN on the osteogenic differentiation of hASCs in GHA microgels. The second phase of the research presents an injectable nanocomposite hydrogel composed of hyaluronic acid, gelatin, and aminated bioactive mesoporous glass nanoparticles (AMBG) for the localized delivery of ALN. Hyaluronic acid/gelatin (HG) hydrogels were prepared after modifying hyaluronic acid and gelatin with tyramine. Nanocomposite hydrogels were fabricated by incorporating varying concentrations of AMBG into the HG hydrogel. Adding AMBG significantly affected the physical and biomechanical properties of the hydrogels. The hydrogel containing 0.5% AMBG demonstrated the highest compressive strength compared to other formulations. The bioactivity properties of this hydrogel were confirmed by the formation of an apatite layer on the hydrogel surface after incubation in simulated body fluid. Also, biological characterization of the resulting hydrogels showed the enhancing effect of AMBG nanoparticles on the osteogenic differentiation of osteoblast-like cells (MC3T3-E1). ALN loading in nanocomposite hydrogels also reduced the differentiation of macrophage cells (RAW 264.7) into osteoclasts in a dose-dependent manner. These results demonstrate the potential of these nanocomposite hydrogels for repairing osteoporotic injuries
  9. Keywords:
  10. Tissue Engineering ; Bone Tissue Engineering ; Hydrogel ; Bioactive Glass ; Microgel ; Alendronate ; Bioactive Scaffold

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