Design and Optimization of Angiogenic, Antibacterial Si-Zn-Hydroxyapatite for Use as Filler Particles in Polycaprolactone Nanocomposites
The development of synthetic biomaterials that replicate the biological functionality and mechanical resilience of native bone remains a central challenge in tissue engineering. Hydroxyapatite (HAp) is a widely used osteoconductive ceramic, but clinical outcomes can be limited by relatively low levels of bioactivity, inherent brittleness, slow in vivo resorption, and susceptibility to post-operative infection. This thesis establishes a mechanistically informed framework for engineering multifunctional bone-regenerative materials by controlling properties from atomic-scale structure and chemistry to macroscopic behaviour. Phase-pure, thermally stable ion-doped HAp was synthesized via aqueous precipitation. Co-doping with silicon and zinc (Si-Zn-HAp) was optimized through control of stoichiometry and processing conditions, and this work extended the previously reported Zn solubility limit in HAp, enabling the formation of continuous solid solutions containing up to 1.35 wt% Si and 0.96 wt% Zn without secondary phase formation. Comprehensive characterization using Rietveld refinement and spectroscopic analyses confirmed that Si and Zn substitutions induce distinct, predictable changes in lattice parameters and microstructure, providing a platform for subsequent biological investigation. In vitro co-cultures of human osteoblasts (hOBs) and human dermal microvascular endothelial cells (hDMECs) on dense Si-Zn-HAp surfaces revealed that osteogenic and angiogenic activity are governed primarily by surface properties rather than direct ionic stimulation. Si substitution resulted in the refinement of the surface grain structure and significantly enhanced hOB proliferation, as well as the self-assembly of endothelial cells into vessel-like structures. Notably, co-doping with Si neutralized an otherwise inhibitory effect of Zn on vasculogenesis, yielding a synergistic enhancement of both osteogenic and angiogenic potential in the Si-Zn-HAp system. The prevailing hypothesis for the antibacterial action of Zn-doped HAp was challenged. Nanoparticles of both doped and undoped HAp exhibited bacteriostatic activity against Staphylococcus aureus, yet Zn-doped variants were consistently less effective than their Si-doped or undoped counterparts. Ion release studies confirmed that Zn2+ concentrations in bacterial media were minimal and did not correlate with antibacterial efficacy. These results indicate that the primary antibacterial mechanism arises from a complex interplay of nanoparticle surface properties, including size and electrochemistry, rather than from ion leaching. To translate these optimized properties into a mechanically resilient format, the Si-Zn-HAp nanoparticles were incorporated into a poly(ε-caprolactone) (PCL) matrix. A novel fabrication strategy, combining short-chain poly(ethylene glycol) (PEG) end-functionalization of PCL with an antisolvent precipitation method, was developed to overcome typical challenges of filler agglomeration and poor interfacial adhesion. This approach yielded nanocomposites with homogeneous nanoparticle dispersion, effectively mitigating the common trade-off between stiffness and toughness. Compared to unmodified PCL composites, the PCL-PEG/Si-Zn-HAp systems exhibited simultaneously higher tensile modulus and yield strength, a two- to fourfold increase in ductility, and controllably accelerated hydrolytic degradation. This work establishes a design paradigm for bone-regenerative materials, demonstrating that the deliberate control of composition and interfacial properties over empirical screening enables the creation of biomimetic composites with tailored biological functionality and mechanical performance.
Biomaterials, Hydroxyapatite, Ion-Doping, Composites, Materials Science
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