PhD Thesis Defense: Levi Olevsky

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"A Biomimetic Scaffold to Support Vascularized Bone Regeneration for Mandibular Defects"

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 face complementary limitations: cryogels offer ideal porosity and biocompatibility but are mechanically too weak for large defects, while 3D-printed scaffolds provide structural strength but lack the resolution needed for optimal tissue ingrowth. This thesis presents the development of a modular, bioactive 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 cryogel porosity and swelling behavior while significantly enhancing mechanical strength. Limitations in elasticity, swelling capacity, and potential cytotoxicity motivated a shift to beta-tricalcium phosphate (β-TCP), a bioresorbable ceramic with established osteoconductivity, as the structural component.

The second study assessed biological performance of the β-TCP/cryogel composite by seeding scaffolds with HUVECs, MSCs, or a HUVEC–MSC coculture across three scaffold types: cryogel alone, 3D-printed lattice alone, and the composite. Cell viability was assessed via CCK-8 assay and immunofluorescence imaging. The HUVEC–MSC coculture exhibited synergistic effects across all scaffold types, confirming the composite's capacity to support the multicellular crosstalk necessary for vascularized bone formation.

Having established a cellularly viable composite, the third study optimized scaffold architecture and sintering parameters. Lattice geometries were screened computationally and fabricated with varying mineral concentration (40–50%) and sintering temperature (1200–1300°C), then evaluated by shrinkage, SEM morphology, and compression testing. Top designs were infiltrated with cryogel and characterized by pore analysis, mechanical testing, swelling, and cell studies.

Together, these studies establish a rational design framework for ceramic–cryogel composite scaffolds, advancing a clinically translatable platform for craniofacial bone reconstruction.

Thesis Committee

• Katherine Hixon (Chair)
• Alexander Boys
• Eric Holmgren, Linqing Li (UNH)

Contact

For more information, contact Thayer Registrar at thayer.registrar@dartmouth.edu.