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Fabrication of a 3D-Printed Scaffold Containing Zoledronic Acid-Loaded Mesoporous Bioactive Glass Particles for Applications in Repairing Defects Caused by Osteoporosis

Fathi, Fatemeh | 2026

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  1. Type of Document: M.Sc. Thesis
  2. Language: Farsi
  3. Document No: 58859 (06)
  4. University: Sharif University of Technology
  5. Department: Chemical and Petroleum Engineering
  6. Advisor(s): Mashayekhan, Shohreh
  7. Abstract:
  8. Osteoporosis, characterized by reduced bone mineral density and deterioration of bone microarchitecture, significantly increases fracture risk, and the limitations of current pharmacological therapies highlight the urgent need for smart bone regeneration systems. Accordingly, the present study aimed to develop a multifunctional, bioactive, and controllable scaffold system by integrating advanced materials with three-dimensional (3D) printing technology for the repair of osteoporotic defects. In the first phase, mesoporous bioactive glass nanoparticles (MBGNPs) with an average diameter of 210 ± 2.8 nm were synthesized and characterized via EDX, XRD, FTIR, BET, and zeta potential analyses. To enhance bioactivity, copper, strontium, and zinc were incorporated as divalent bioactive dopants, improving angiogenic, immunomodulatory, and osteogenic properties while reducing the mean particle size to 57.5±1.3 nm. The doped MBGNPs were surface-functionalized with thiol groups and incorporated into polycaprolactone (PCL) to prepare a bioink suitable for 3D printing of nanocomposite scaffolds under ambient conditions. Subsequently, for the first time, metal–organic frameworks (MOFs) loaded with zoledronic acid, exhibiting cubic morphology and dimensions of ~1 µm, were synthesized and characterized using SEM, EDAX, FTIR, and XRD. The previously printed scaffolds were coated via immersion in the MOF-containing solution. Stable attachment of these MOFs to the nanocomposite substrate was achieved through a thiol–ene click reaction between thiol groups on MBGNPs and the C=C double bonds within the imidazole ring of zoledronic acid under UV irradiation for 8, 16, and 24 h, as confirmed by ATR-FTIR analysis. This strategy enabled drug loading of 0.32, 0.49, and 0.92 mg per scaffold for 8, 16, and 24 h irradiation, respectively, while minimizing burst release in the relatively acidic defect microenvironment and permitting controlled, targeted delivery to effectively inhibit osteoclast activity. Simultaneously, the gradual release of doped ions from MBGNPs modulated immune responses, promoted osteogenic signaling, and enhanced angiogenesis, collectively supporting bone tissue regeneration. After two weeks, the presence of MBGNPs induced the formation of hydroxyapatite crystals, as confirmed by electron microscopy. Overall, this study successfully developed next-generation, multifunctional 3D-printed scaffolds exhibiting mechanical strength of ~75.1 MPa, controlled drug release, effective bioactive ion delivery for osteoporosis treatment, and demonstrated excellent biocompatibility as confirmed by MTT assay
  9. Keywords:
  10. Osteoporosis ; Mesoporous Nanoparticles ; Bioactive Glass ; Metal-Organic Framework ; Three Dimentional Printing Scaffold ; Mesoporous Bioactive Glass Nanoparticles (MBGNPs)

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