Date of Completion

1-15-2019

Embargo Period

1-14-2020

Keywords

Tissue Engineering; Tendon; Insulin; Scaffolds; Polycaprolactone; Cellulose Acetate; Electrospun Fibers; Micro-nanostructures; Insulin Delivery

Major Advisor

Sangamesh G. Kumbar

Co-Major Advisor

Cato T. Laurencin

Associate Advisor

Augustus D. Mazzocca

Associate Advisor

Yusuf Khan

Associate Advisor

Syam P. Nukavarapu

Field of Study

Materials Science and Engineering

Degree

Doctor of Philosophy

Open Access

Open Access

Abstract

Tendon injuries account for roughly half of the 33 million musculoskeletal injuries that occur every year. Of all patients seeking nonsurgical treatment, 29% eventually require surgery. The use of autografts, allografts, and xenografts have limitations associated with donor site morbidity, availability, and immunogenicity. Tissue engineering has emerged as a feasible approach to find treatments for injuries requiring tissue replacement through biodegradable scaffolds, stem cells, and biomolecules.

Tissue engineering scaffolds serve to provide a temporary, biomimetic template for cells, as well as act as delivery vehicles for biomolecules, such as growth factors. Growth factors have been widely popular in tissue engineering owing to their importance in embryonic development and healing. Insulin-like growth factor-1 (IGF-1) has been extensively researched for its ability to encourage cell proliferation, inhibition of cell apoptosis, and collagen formation. The homology of insulin and IGF-1, structurally, as well as biologically, has motivated various comparative studies, as well as investigations in the use of insulin for tissue engineering applications. This work explored insulin as a bioactive factor in promoting tendon regeneration and investigated insulin delivery through electrospun blend fibers made from synthetic polymer, polycaprolactone and natural material, cellulose acetate.

The treatment of human mesenchymal stem cells (MSCs) with concentration of 100ng/ml showed increased expression of tendon related genes and ECM proteins, suggesting phenotypic development of MSCs towards tendon lineage. Insulin functionalized scaffolds were observed to support tendon differentiation of MSCs, in-vitro. The bioactive scaffolds were implanted in a rat Achilles tendon model and found to encourage better healing through greater collagen deposition and fiber organization. However, no significant findings were found in mechanical properties of the healed tissue when compared to control groups. Increase in collagen and matrix organization with no difference in mechanical property warrants further research in functional analysis of the tendon and exploration into possible early immunomodulation effects. For the first time, insulin has been investigated for use in tendon tissue engineering applications and shown to achieve better ECM organization with use of a bioactive insulin functionalized scaffold.

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