Author ORCID Identifier

https://orcid.org/0000-0002-1415-1577

Date of Award

Spring 5-20-2026

Document Type

Thesis (Ph.D.)

Department or Program

Engineering Sciences

First Advisor

Katherine Hixon

Abstract

Mandibular defects present a significant reconstructive challenge requiring both mechanical support and biological integration. Autografts are limited by donor site morbidity and surgical complexity, while existing scaffold alternatives present opposing shortcomings: cryogels offer ideal porosity and biocompatibility but lack mechanical strength, while 3D-printed scaffolds provide structural strength but fail to replicate the hydrated, cell-permissive microenvironment. This thesis presents the development of a composite scaffold combining 3D-printed ceramics with polymer cryogels to promote vascularized bone regeneration, addressed through three studies: establishing composite feasibility, validating multicellular biological response, and optimizing scaffold architecture and sintering parameters. The first study integrated 3D-printed polymer lattices with chitosan–gelatin cryogels, preserving porosity and swelling behavior while significantly enhancing mechanical strength. Limitations in elasticity, swelling capacity, and potential cytotoxicity motivated a shift to beta-tricalcium phosphate, a bioresorbable ceramic with established osteoconductivity, as the structural component. The second study assessed biological performance of the β-TCP/cryogel composite across three scaffold types seeded with HUVECs, bMSCs, or coculture. The β-TCP lattice drove early osteogenic marker expression, while HUVEC–bMSC coculture produced a branching CD31 pattern consistent with endothelial cord formation alongside parallel osteogenic differentiation, confirming the composite's capacity to support coupled vascularization and mineralization. Preliminary murine cranial defect implantation demonstrated enhanced tissue ingrowth relative to empty defect controls. The third study optimized scaffold architecture and sintering parameters through computational screening using geometric filtering, finite element simulation, and AHP-based ranking. The Diamond lattice at 45% mineral loading and 1250°C was identified as optimal, balancing mechanical integrity, dimensional accuracy, and microstructural consolidation. Dimensional shrinkage was geometry-independent across all architectures, supporting a universal shrinkage compensation factor for patient-specific design. Patient-specific modeling confirmed that the gyroid-based composite can be adapted to diverse mandibular defect morphologies. Together, these studies establish a rational design framework for ceramic–cryogel composite scaffolds, advancing a clinically translatable platform for craniomaxillofacial bone reconstruction.

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