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Aditi's Thesis
Embargoed Access, Embargo ends: 08/26/2026
Dissertation
CONTROLLED RELEASE OF PHYTOCHEMICALS FROM CALCIUM PHOSPHATE SCAFFOLDS FOR BONE REGENERATION
Doctor of Philosophy (PhD), Washington State University
2025
Abstract
Critical-sized bone defects arising from trauma, infection, and tumor resection remain a major challenge due to the limited regenerative capacity of bone and the low availability of grafts. Existing bone grafts lack the multifunctionality needed to simultaneously drive osteogenesis, support angiogenesis, control infection, and prevent tumor recurrence. This research addresses these unmet needs by developing multifunctional biomaterial platforms that integrate phytochemicals such as Carvacrol/ Curcumin and their derivatives into ceramic scaffolds for bone tissue engineering. Carvacrol is incorporated into hydroxyapatite substrates, where it suppresses osteoclasts, enhances osteogenesis in vivo, and supports vascularization. To improve functionality, carvacrol is modified into an aldehyde derivative (CA-CHO) via ortho-formylation. CA-CHO exhibits antibacterial activity against S. aureus and induces cytotoxicity in osteosarcoma cells. Building on these results, carvacrol-derived Schiff base Cu²⁺ complexes, lipid nanoparticle encapsulation, and dual-drug formulations are investigated. Carvacrol-loaded LNPs incorporated into 3DP SiO₂-doped TCP scaffolds demonstrate bacterial inhibition, osteoblast support, and osteosarcoma suppression in vitro. Nanoparticles co-loaded with carvacrol and curcumin using melt emulsification. In vitro studies showed a 1.4-fold increase in osteoblast cell viability with CC-NP treatment, promoting bone regeneration. CC-NPs exhibit cytotoxic effects against osteosarcoma cells, reducing viability by ~2.9-fold. A curcumin-Mg²⁺ complex is integrated into 3DP TCP scaffolds, shifting release behavior from burst to sustained profiles and promoting osteogenesis, suppressing osteoclast activity, enhancing angiogenesis, and generating ~2-fold more new bone than the control in vivo. Together, these findings establish a framework for the rational design of multifunctional biomaterials with broad potential in musculoskeletal regenerative medicine.
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Details
- Title
- CONTROLLED RELEASE OF PHYTOCHEMICALS FROM CALCIUM PHOSPHATE SCAFFOLDS FOR BONE REGENERATION
- Creators
- Aditi Dahiya
- Contributors
- Susmita Dr. Bose (Advisor)Amit Dr. Bandyopadhyay (Committee Member)Anjali Dr. Sharma (Committee Member)Jeffrey Dr. Bell (Committee Member)
- Awarding Institution
- Washington State University
- Academic Unit
- Department of Chemistry
- Theses and Dissertations
- Doctor of Philosophy (PhD), Washington State University
- Number of pages
- 363
- Identifiers
- 99901356972401842
- Language
- English
- Resource Type
- Dissertation