Date Approved

8-18-2022

Embargo Period

8-22-2022

Document Type

Dissertation

Degree Name

Ph.D. Doctor of Philosophy

Department

Biomedical Engineering

College

Henry M. Rowan College of Engineering

Advisor

Peter A. Galie, Ph.D.

Committee Member 1

Erik C. Brewer, Ph.D.

Committee Member 2

Paul A. Janmey, Ph.D.

Committee Member 3

Alan Turtz, M.D.

Committee Member 4

Sebastian L. Vega, Ph.D.

Keywords

3D-printing, Angiogenesis, Magnetism, Spinal cord injury, Tissue engineering, Vascularized scaffolds

Subject(s)

Tissue scaffolds; Spinal cord--Wounds and injuries

Disciplines

Biomedical Engineering and Bioengineering

Abstract

Scaffolds delivered to injured spinal cords to stimulate axon connectivity often act as a bridge to stimulate regeneration at the injured area, but current approaches lack the permissiveness, topology and mechanics to mimic host tissue properties. This dissertation focuses on bioengineering scaffolds through the means of altering topology in injectables and tuning mechanics in 3D-printed constructs as potential therapies for spinal cord injury repair. A self-assembling peptide scaffold, RADA-16I, is used due to its established permissiveness to axon growth and ability to support vascularization. Immunohistochemistry assays verify that vascularized peptide scaffolds promote axon infiltration, attenuate inflammation and reduce astrogliosis. Furthermore, magnetically-responsive (MR) RADA-16I injections are patterned along the rostral-caudal direction in both in-vitro and in-vivo conditions. ELISA and histochemical assays validate the efficacy of MR hydrogels to promote and align axon infiltration at the site of injury. In addition to injectable scaffolds, this thesis uses digital light processing (DLP) to mimic the mechanical heterogeneity of the spinal cord caused by white and gray matter, and demonstrate that doing so improves axon infiltration into the scaffold compared to controls exhibiting homogeneous mechanical properties. Taken together, this work contributes to advancing the field of tissue engineering and regenerative medicine by demonstrating the potential of bioengineered scaffolds to repair the damaged spinal cord.

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