Date Approved

6-21-2021

Embargo Period

6-23-2022

Document Type

Thesis

Degree Name

M.S. Biomedical Engineering

Department

Biomedical Engineering

College

Henry M. Rowan College of Engineering

Advisor

Sebastián L. Vega. Ph.D.

Committee Member 1

Tae Won Kim, MD

Committee Member 2

Eric Brewer, Ph.D.

Committee Member 3

Mary Staehle, Ph.D.

Committee Member 4

Vincent Beachley, Ph.D.

Keywords

methacrylated gelatin (GelMe) hydrogel, osteochondral, osteoarthritis, composite, polycaprolactone (PCL), mesenchymal stem cells (MSCs)

Subject(s)

Tissue engineering; Regenerative medicine

Disciplines

Biomedical Engineering and Bioengineering

Abstract

Biophysical signals including stiffness and dimensionality influence a myriad of stem cell behaviors including morphology, mechanosensing, and differentiation. 2D stiff environments cause increased cellular spreading and induce osteogenic differentiation whereas 3D soft environments favor rounder cell morphologies attributed to a chondrogenic phenotype. The goal of this study is to create a composite that integrates these divergent biophysical signals within one system. This composite consists of a stiff and porous polycaprolactone (PCL) backbone that provides mechanical stiffness and a 2D environment. The PCL backbone is then perfused with mesenchymal stem cells (MSCs) and a soft methacrylated gelatin (GelMe) hydrogel to provide an encapsulation technique that exposes cells to a soft 3D environment. Interestingly, MSCs in these composites exhibited differences in morphology and mechanosensing based on pore diameter. MSCs cultured in low pore size (~275µm) composites were larger and more mechanically active than MSCs in high pore size (~425µm) composites. Our finite element analysis models suggest that the role of pore size on cellular mechanosensing is linked to local changes in hydrogel stress from PCL-GelMe interactions. This composite is currently being explored for engineering the osteochondral tissue interface which contains a mixed population of osteoblasts and chondrocytes.

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