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CALCIUM PHOSPHATE-BASED IMPLANTS WITH NATURAL MEDICINES AND ESSENTIAL ELEMENTS FOR BONE REGENERATION
Dissertation

CALCIUM PHOSPHATE-BASED IMPLANTS WITH NATURAL MEDICINES AND ESSENTIAL ELEMENTS FOR BONE REGENERATION

Priya Kushram
Doctor of Philosophy (PhD), Washington State University
2026
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Thesis-Priya Kushram copy
Embargoed Access, Embargo ends: 07/17/2027

Abstract

Bioceramics Bone Regeneration Drug Delivery Natural Medicinal Compounds Titanium Implant Tricalcium Phosphate
The objective of this research is to develop multifunctional calcium phosphate–based implants capable of providing mechanical support, controlled therapeutic delivery, antibacterial activity, and anticancer efficacy for orthopedic and dental applications. Hydroxyapatite (HA)-coated Ti6Al4V implants and binder-jet 3D-printed tricalcium phosphate (TCP)-based scaffolds were engineered to enable sustained, localized release of natural medicinal compounds and trace elements, and their effects on osteogenesis, tumor suppression, angiogenesis, and infection control were systematically evaluated.RF induction plasma–sprayed HA coatings (~200 µm thick) loaded with curcumin and epigallocatechin gallate (EGCG) demonstrated controlled release under acidic (pH 5.0) and physiological (pH 7.4) conditions for up to 16 days. Dual-drug delivery resulted in up to 93% reduction in osteosarcoma (MG-63) cell viability and a ~3-fold increase in osteoblast (hFOB) proliferation compared to controls. Antibacterial studies showed up to 94% reduction in Staphylococcus aureus viability within 72 hours. Binder-jet 3D-printed TCP scaffolds with a designed ~400 µm interconnected porosity were functionalized with garlic extract nanoemulsions (average particle size ~158 nm), allicin, quercetin, and ZnO. Sustained release was achieved for up to 21–30 days, depending on the formulation. Garlic nanoemulsion–loaded scaffolds demonstrated up to 88% reduction in MG-63 viability and 87–93% reduction in S. aureus and Pseudomonas aeruginosa colonies. Quercetin- and ZnO-functionalized scaffolds enhanced osteoblast activity, reduced osteoclast resorption pit area, and significantly upregulated osteogenic genes (RUNX2, ALPL, BGLAP) while downregulating osteoclastic markers. In vivo rat distal femur defect models showed increased new bone formation, mineralized bone area, and vascular density at 6 weeks compared to control scaffolds. Nanostructured lipid carrier systems enabled pH-responsive release of quercetin and further improved osteogenic gene expression and bone regeneration outcomes. TCP–bioglass composite scaffolds exhibited improved compressive strength while maintaining sustained release and biological performance. This work demonstrates that controlled, localized delivery of natural compounds and trace elements from HA-coated titanium implants and 3D-printed TCP scaffolds can achieve simultaneous tumor inhibition (>90%), antibacterial efficacy (>90%), and enhanced bone regeneration in vitro and in vivo. These findings support the development of multifunctional therapeutic implants for complex orthopedic and dental reconstruction.

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