Abstract
Bone tissue engineering aims to restore or replace bone defects through the integration of biomaterial scaffolds with appropriate structural and biological cues. However, the repair of complex or large bone defects remains challenging due to the need to simultaneously achieve sufficient mechanical stability, effective mass transport, and a biologically supportive microenvironment. In this thesis, a biomimetic channel-pillar porous scaffold was developed to address these challenges through architectural optimisation and material functionalisation.
A series of polycaprolactone scaffolds featuring vertically and horizontally aligned channels reinforced by pillar structures were designed and fabricated by three-dimensional printing. By systematically varying the internal geometry, the influence of channel-pillar configurations on porosity, interconnectivity, and mechanical performance were investigated. The results demonstrated that the introduction of pillar-supported channels significantly enhanced compressive strength while maintaining favourable permeability, with triangular pillar geometries providing superior load-bearing performance. These scaffolds also supported effective mesenchymal stem cell attachment and spreading, indicating good biocompatibility.
Building upon the optimised structural design, the scaffold composition was further modified to enhance its biological functionality. Hydroxyapatite and mānuka oil derived triketone were incorporated into the polycaprolactone matrix to improve osteogenic potential and confer antimicrobial activity. Physicochemical characterisation confirmed that these modifications preserved structural integrity while improving surface properties relevant to cell material interactions. In vitro studies demonstrated enhanced osteogenic differentiation of mesenchymal stem cells, promoted tube formation of endothelial, and effective antimicrobial performance, highlighting the multifunctional capacity of the modified scaffolds.
The optimised scaffold’s regenerative potential was subsequently evaluated in vivo using both small and large animal models. Short term subcutaneous implantation for two weeks in rats demonstrated favourable tissue integration and minimal inflammatory response, while long term implantation for twelve weeks in a sheep femoral defect model revealed robust bone formation under physiological loading conditions. Micro-computed tomography and histological analyses showed that new bone formation progressed inward along the channel guided pathways, closely resembling native bone healing patterns and confirming effective regeneration.
Overall, this research demonstrates that the rational integration of channel-pillar architecture with targeted material functionalisation can yield a mechanically robust and biologically active scaffold capable of supporting both osteogenesis and angiogenesis. The findings provide a strong foundation for the clinical translation of multifunctional 3D printed bone scaffolds to treat the large or challenging bone defects.