Bioresponsive hydrogels are emerging with technological significance in targeted drug delivery, biosensors and regenerative medicine. The design challenge is to effectively link the conferred biospecificity with an engineered response tailored to the needs of a particular application. Moreover, the fundamental phenomena governing the response must support an appropriate dynamic range, limit of detection and the potential for feedback control. The design of these systems is inherently complicated due to the high interdependency of the governing phenomena that guide sensing, transduction and actuation of the hydrogel. The objective of the dissertation is to review the current state of bioresponsive hydrogel technology and introduce a method of extending the technology through integrated control loops; explore fundamental phenomena which affect ion transport within biomimetic hydrogels; and investigate, via in silico studies, the fundamental design parameters for the implementation of a feedback control loop within a bioresponsive hydrogel.
In one study, effects of valence number, temperature and polymer swelling on release profiles of monovalent potassium and divalent calcium ions elucidates mechanistic characteristics of polymer interactions with charged species. For comparison, ions were loaded during hydrogel formulation or loaded by partitioning following construct synthesis. Using the Korsmeyer-Peppas release model, the diffusional exponents were found to be Fickian for pre- and post-loaded potassium ions while preloaded calcium ions followed an anomalous behavior and postloaded calcium ions followed Case II behavior. Results indicate divalent cations interact through cation-polyelectrolyte anion complexation while monovalent ions do not interact with the polymer. Temperature dependence of potassium ion release was shown to follow an Arrhenius relation and calcium ion release was temperature independent.
In another study, data generated from the previous Chymotrypsin system is used to build and validate a finite element model. The model provides insight into key engineering parameters for the design of an enzymatically actuated, feedback controlled release. A drug delivery platform comprising a biocompatible, bioresponsive hydrogel and possessing a covalently tethered peptide-inhibitor conjugate was engineered to achieve stasis, via a closed control loop, of the external biochemical activity of the actuating enzyme. The FEM model was used to investigate the release of a competitive protease inhibitor, MAG283, via cleavage of Acetyl-Pro-Leu-Gly|Leu-MAG-283 by MMP-9 in order to achieve targeted homeostasis of MMP-9 activity, a goal for the treatment of chronic wound pathophysiology. It was found the key engineering parameters for the delivery device are the radii of the hydrogel microspheres and the concentration of the peptide-inhibitor conjugate loaded into the hydrogel.
Homeostatic drug delivery, where the focus turns away from the drug release rate and turns towards achieving targeted control of biochemical activity within a biochemical pathway, is an emerging approach in drug delivery methodologies for which the potential has not yet been fully realized. By understanding mechanistic phenomena and key engineering parameters for design, advancements in bioresponsive hydrogels will continue to produce novel technologies in biomedical applications.
Some files may require a special program or browser plug-in. More Information
|Commitee:||Blenner, Mark A., Kitchens, Christopher L., Lee, Jeoung Soo, Roberts, Mark E.|
|Department:||Chemical and Biomolecular Engineering|
|School Location:||United States -- South Carolina|
|Source:||DAI-B 75/10(E), Dissertation Abstracts International|
|Subjects:||Biomedical engineering, Chemical engineering, Pharmacy sciences|
|Keywords:||Bioresponsive hydrogel, Control loop, Drug release, Ion transport, Polyplex, Self regulating systems|
Copyright in each Dissertation and Thesis is retained by the author. All Rights Reserved
The supplemental file or files you are about to download were provided to ProQuest by the author as part of a
dissertation or thesis. The supplemental files are provided "AS IS" without warranty. ProQuest is not responsible for the
content, format or impact on the supplemental file(s) on our system. in some cases, the file type may be unknown or
may be a .exe file. We recommend caution as you open such files.
Copyright of the original materials contained in the supplemental file is retained by the author and your access to the
supplemental files is subject to the ProQuest Terms and Conditions of use.
Depending on the size of the file(s) you are downloading, the system may take some time to download them. Please be