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STUDIES IN THE DEVELOPMENT OF A XENOGRAFT-DERIVED BONE SCAFFOLD

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abstract
Bone grafts are used in nearly one half of all musculoskeletal surgeries and represent an enormous health care expenditure. Tissue-engineered bone graft substitutes have garnered considerable attention to alleviate the risk of bone graft harvest and potential for disease transmission. Xenografts sources are an attractive alternative because of their relatively unlimited supply from a pool of healthy donors but have historically been limited by the alpha-Gal epitope which may lead to immune system rejection of the graft. In the presented dissertation, we derive a bone scaffold from the cancellous bone of porcine (pig) femurs using a novel decellularization and chemical oxidation protocol. In the following chapters we discuss the development and characterization of this bone scaffold. The presented results show the decellularization protocol is able to efficiency remove porcine cellular material to yield a scaffold that is devoid of cellular material and has similar biology and biomechanical properties to the starting cancellous bone. In vitro studies show the scaffold is biocompatible and free of contaminating pathogens supporting its consideration for further investigation. Molecular studies demonstrate that a substantial proportion of the alpha-Gal epitope is removed from source bone with the decellularization protocol. Lastly we show that the scaffold possesses some degree of osteoinductive potential that may direct undifferentiated cells towards an osteoblastic lineage and promote bone regeneration. A xenograft-derived bone scaffold has the potential to alleviate the patient morbidity imparted by autograft bone harvest, eliminate the risk of disease transmission associated with allograft bone transplantation, and satisfy the currently unsatisfied demand for bone graft products in the United States.
subject
Bone Scaffold
Decellularized
Tissue Engineering
Xenograft
contributor
Bracey, Daniel Nicholas (author)
Smith, Thomas L (committee chair)
Register, Thomas C (committee member)
Willey, Jeffrey S (committee member)
Koman, L Andrew (committee member)
Van Dyke, Mark E (committee member)
Smith, Thomas L (committee member)
date
2017-06-15T08:35:51Z (accessioned)
2019-06-14T08:30:13Z (available)
2017 (issued)
degree
Molecular Medicine and Translational Science (discipline)
embargo
2019-06-14 (terms)
identifier
http://hdl.handle.net/10339/82186 (uri)
language
en (iso)
publisher
Wake Forest University
title
STUDIES IN THE DEVELOPMENT OF A XENOGRAFT-DERIVED BONE SCAFFOLD
type
Dissertation

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