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Graduate Defense: Alexander Regner

April 14 @ 12:00 pm - 1:00 pm MDT

Thesis Information

Title: 3D Printable Models of Bone Marrow Mechanical Environment

Program: Master of Science in Materials Science and Engineering

Advisor: Dr. Gunes Uzer, Mechanical and Biomedical Engineering

Committee Members: Dr. Clare Fitzpatrick, Mechanical and Biomedical Engineering, Dr. Danielle Wu, Materials Science and Engineering, Dr. David Estrada, Materials Science and Engineering and Electrical and Computer Engineering, and Dr. Trevor Lujan, Mechanial and Biomedical Engineering

Abstract

Aged individuals and astronauts experience bone loss despite rigorous physical activity. Bone mechanoresponse is in part regulated by mesenchymal stem cells (MSCs). We reported daily low intensity vibration (LIV) restores MSC proliferation in senescence and simulated microgravity models, suggesting reduced mechanical signal delivery to MSCs likely contributes to declining bone mechanoresponse. To this end, we have developed a 3D bone marrow analog which controls trabecular geometry, marrow mechanics and external stimuli.

Finite element (FE) models of hydrogels, representing bone marrow, were generated using instantaneous compression (1000% strain/s, 20% strain) and relaxation experiments (100s) of both gelatin and hyaluronin-based hydrogels. Experimental and in silico vibration experiments using molded-gelatin wells (widths=3, 4, 5, 6 and 8 mm) were performed under 1g acceleration, 100 Hz for FE model calibration.

For MSC experiments, 0.25cm3 gyroid-based trabeculae of bone volume fractions (BV/TV)3 corresponding to adult (25%) and aged (13%) mice were printed using polylactic acid. MSCs encapsulated (1×106 cells/mL) in migration-permissive hydrogels within printed trabeculae were exposed to LIV (1g, 100 Hz, 1 hour/day). After 14 days, type-I collagen, Ki-67, f-actin (n=3/grp) were quantified for extracellular matrix composition, proliferation, and morphology and grouped with respect to the maximum von Mises strain for 13% and 25% BV/TV scaffolds using the calibrated FE models.