CONTROLLED RELEASE OF PHYTOCHEMICALS FROM CALCIUM PHOSPHATE SCAFFOLDS FOR BONE REGENERATION
Aditi Dahiya
Doctor of Philosophy (PhD), Washington State University
12/2025
DOI:
https://doi.org/10.7273/000008364
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Abstract
Aldehyde derivative Regenerative medicine Osteosarcoma cells Biomaterial platforms Trauma
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 orthoformylation. 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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Title
CONTROLLED RELEASE OF PHYTOCHEMICALS FROM CALCIUM PHOSPHATE SCAFFOLDS FOR BONE REGENERATION
Creators
Aditi Dahiya
Contributors
Susmita Bose (Chair)
Amit Bandyopadhyay (Committee Member)
Anjali Sharma (Committee Member)
Jeffrey Bell (Committee Member)
Awarding Institution
Washington State University
Academic Unit
Department of Chemistry
Theses and Dissertations
Doctor of Philosophy (PhD), Washington State University