Date

8-1-2019

Document Type

Thesis

Degree

Master of Science

Department

Materials Science and Engineering

First Adviser

Lesley W. Chow

Abstract

Each year, millions of people worldwide suffer from organ failure or tissue loss due to injury, disease, or congenital malformation. With a progressively aging population and limited supply of donor tissues and organs, there is increasing demand for therapies to regenerate or replace tissues long-term. Tissue engineering has emerged as a promising approach to restore, maintain, or improve damaged tissues or whole organs by providing lab-grown replacements or promoting tissue regeneration. Biodegradable polymer-based scaffolds are widely used in tissue engineering strategies to provide support during early stages of regeneration and are commonly functionalized with various chemical groups or bioactive cues to promote desired cellular behavior. However, these functionalized scaffolds are often modified post- fabrication, which can lead to undesired changes and homogeneously distributed chemistries that fail to mimic the spatial biochemical organization found in native tissues. To address these challenges, surface functionalization can be achieved by 3D printing with pre-functionalized biodegradable polymers, such as peptide-modified polymer conjugates, to control the spatial deposition of preferred chemistries. In this work, peptide-PCL conjugates were synthesized with the canonical cell adhesion peptide motif RGDS or its negative control RGES and 3D printed into scaffolds displaying one or both peptides. The peptides were also modified with bioorthogonal groups, biotin and azide, to visualize peptide concentration and location by labeling with complementary fluorophores. Peptide concentration on the scaffold surface increased with increasing peptide-PCL conjugate concentration added to the ink prior to 3D printing, and scaffolds printed with the highest RGDS(biotin)-PCL concentrations showed a significant increase in NIH3T3 fibroblast adhesion and spreading. To demonstrate spatial control of peptide functionalization, multiple printer heads were used to print both peptide-PCL conjugates into the same construct in alternating patterns. Cells preferentially attached and spread on RGDS(biotin)-PCL fibers compared to RGES(azide)-PCL fibers, illustrating how spatial functionalization can be used to influence local cell behavior within a single biomaterial. This presents a versatile platform to generate multifunctional biomaterials that can mimic the biochemical organization found in native tissues to support functional regeneration.

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