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Abstract: Segmental mandibular bone loss presents a significant reconstructive challenge due to the need for both mechanical support and biological integration. While autografts are the clinical gold standard, they are limited by donor site morbidity, poor anatomical fit, and surgical complexity. This thesis will aim to develop a modular, bioactive scaffold platform that combines the structural integrity of 3D-printed ceramics with the bioactivity and cell-instructive properties of cryogels to promote vascularized bone regeneration.

Initial work established a hybrid scaffold by integrating 3D-printed polymer lattices with chitosan–gelatin cryogels. This combination preserved the high porosity and swelling behavior of cryogels while significantly enhancing mechanical strength and enabling patient-specific geometries. However, limitations in elasticity, swelling capacity, and potential cytotoxicity highlighted the need for an optimized mineral-based system.

To address this, β-tricalcium phosphate (β-TCP) will be used to fabricate mechanically robust, architecturally tunable ceramic lattices. These lattices will be infiltrated with cryogels to create composite scaffolds, which will then be evaluated for print fidelity, mechanical performance, degradation behavior, and anatomical fit. 

Biological performance will be assessed by culturing human umbilical vein endothelial cells (HUVECs) and mesenchymal stem cells (MSCs) on cryogel-only, β-TCP-only, and composite scaffolds in both mono- and co-culture formats. Cell viability, morphology, differentiation, and signaling will be analyzed through imaging, functional assays, and gene and protein expression. Bulk RNA sequencing will be conducted on co-culture groups to identify key signaling pathways involved in bone–vascular crosstalk within the composite environment.

Altogether, this proposed work will establish a framework for designing customizable, mechanically stable, and biologically active scaffolds tailored to mandibular defect repair. The findings are expected to contribute broadly to the development of next-generation regenerative platforms in craniofacial bone tissue engineering.

Thesis Committee: Katherine Hixon (Chair), Alexander Boys, Eric Holmgren, Linqing Li (UNH)