Date of Graduation

12-2025

Document Type

Dissertation

Degree Name

Doctor of Philosophy in Engineering (PhD)

Degree Level

Graduate

Department

Biomedical Engineering

Advisor/Mentor

Almodovar, Jorge

Committee Member

Nelson, Christopher

Second Committee Member

Nayani, Karthik

Third Committee Member

Song, Young Hye

Keywords

Biomaterials; Human Mesenchymal Stromal Cells; Immunomodulation; Polyelectrolyte Multilayers; Proliferation; Regenerative Medicine

Abstract

Cell therapies using human mesenchymal stromal cells (hMSCs) are limited by a manufacturing paradox. That paradox lies in the fact that proliferation is required for clinical scale cell yields, yet that inherently limits their therapeutic capacity. This dissertation aims to validate a bioprocessing platform using Layer-by-Layer (LbL), Heparin and Collagen coatings to address this challenge. They simultaneously act through the JAK/STAT-IDO pathway and the FGFR/ERK pathway, altering the immunomodulatory profile and addressing the proliferation issue, respectively. This functional enhancement is supported by a heightened metabolic state, with LbL cultured hMSCs showing significantly increased basal respiration and ATP production. This platform was successfully scaled from 2D to 3D microcarriers in dynamic spinner flasks, where the coatings increased cell yield and showed favorable metabolic profiles, with a discrete increase in cost. For an 18.6% increase in cost, cell yields increased 30-110%, corresponding to a 9-44% decrease in cost per million cells. This dissertation establishes these LbL-coated microcarriers as a mechanistically defined, economically viable platform with potential as a cGMP-compliant industrial scale platform, capable of offering an effective solution to the critical paradox that hMSCs face.

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