Aptamer-functionalized Hydrogels for the Programmable Release of Growth Factors

Open Access
Author:
Battig, Mark Richard
Graduate Program:
Bioengineering
Degree:
Doctor of Philosophy
Document Type:
Dissertation
Date of Defense:
October 10, 2014
Committee Members:
  • Yong Wang, Dissertation Advisor
  • Yong Wang, Committee Chair
  • Justin Lee Brown, Committee Member
  • Esther Winter Gomez, Committee Member
  • Jian Yang, Committee Member
  • Andrey S Krasilnikov, Committee Member
Keywords:
  • aptamer
  • hydrogel
  • functionalization
  • growth factor
  • protein
  • biomaterial
  • controlled release
Abstract:
Growth factors are potent signaling molecules that regulate numerous physiological processes. However, the safe and efficient delivery of growth factors remains an unmet goal when growth factors are applied to treat various pathologies. To control the spatiotemporal delivery of growth factors, material carriers such as hydrogels have been investigated. Hydrogels are promising growth factor delivery systems for their high water content and similarities to native tissue. However, the high permeability of hydrogel releases the loaded growth factors rapidly. In addition, the release rate of multiple growth factors cannot be controlled individually when multiple growth factors are incorporated. In order to better control the release rates of growth factors from hydrogels, functionalization strategies using affinity ligands should be explored. Nucleic acid aptamers are synthetic oligonucleotides that bind to target molecules with high specificity and high affinity. In addition, these aptamers can be chemically modified with various functional groups and conjugated to a variety of biomaterials. For these reasons, hydrogels functionalized with aptamers could be a valuable tool for controlling the release of growth factors. Two main objectives were pursued in this work: 1) characterizing the molecular interactions of aptamers with cognate biomolecules, and 2) develop aptamer-functionalized delivery systems for the controlled release of growth factors. Modulation of the binding affinity can occur through the introduction or removal of steric hindrance or the use base substitutions. In addition, the use of an oligonucleotide complementary to the aptamer can be used to inactivate the aptamer. The aptamers were then used to develop an aptamer-functionalized system for the high retention and regulated release of growth factors. The work described herein presents a promising method to control growth factor delivery for the treatment of many human diseases.