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Title page for ETD etd-12082016-192218


Type of Document Dissertation
Author Martin, John Robert
Author's Email Address john.r.martin@vanderbilt.edu
URN etd-12082016-192218
Title Poly(thioketal) Polymers and Their Use in the Formation of Hydrophobic and Hydrophilic Cell-Degradable Tissue Engineering Materials
Degree PhD
Department Biomedical Engineering
Advisory Committee
Advisor Name Title
Craig L. Duvall Committee Chair
Hak-Joon Sung Committee Member
Jeffrey M. Davidson Committee Member
Lillian B. Nanney Committee Member
Scott A. Guelcher Committee Member
Keywords
  • wound healing
  • reactive oxygen species
  • regenerative medicine
Date of Defense 2016-12-05
Availability unrestricted
Abstract
The fields of regenerative medicine and tissue engineering are founded on the usage of bulk-scale, biodegradable material implants that help direct the repair of damaged or non-functioning tissues or organs. Biodegradable tissue engineering materials are commonly fabricated with hydrolytically-degradable polyester polymers or enzymatically degradable peptides. However, ester hydrolysis produces acidic byproducts that can trigger an autocatalytic degradation mechanism and accelerated scaffold mechanical failure, while peptide-based biomaterials cannot be affordably synthesized at large scales with current technology. Therefore, there remains an unmet clinical need for biomaterial implants that are specifically degraded by cell-mediated activity but can be inexpensively fabricated in large scales. In this dissertation, a polymer platform technology was developed to fabricate synthetic biomaterials that are specifically degraded by cell-generated reactive oxygen species (ROS). These materials contain poly(thioketal) (PTK) polymers that are selectively sensitive to oxidation, inexpensively synthesized, and can be incorporated into both hydrophobic and hydrophilic tissue engineering materials. Hydrophobic PTK polymers were synthesized and used to fabricate injectable polyurethane tissue engineering scaffolds that demonstrated ROS-dependent degradation both in vitro and in vivo. Additionally, these PTK-based scaffolds improved the healing of excisional wounds in diabetic rats compared to conventional polyester-urethane scaffolds, and could also locally delivery drugs to these diabetic wounds to further enhance tissue regeneration. Finally, water-soluble PTK polymers were synthesized and incorporated into hydrophilic poly(ethylene glycol) (PEG) hydrogels. These injectable PTK hydrogels were degraded by ROS in vitro, successfully encapsulated viable stem cells, and underwent significantly faster in vivo degradation compared to conventional, enzymatically-degradable PEG hydrogels. Overall, the development of ROS-degradable PTK polymers in tissue engineering materials represents an exciting new advance in environmentally-responsive materials and offers a highly translatable biomaterial platform for a number of clinical applications.
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