Programmable hydrogels for cell catch and release
Open Access
- Author:
- Li, Shihui
- Graduate Program:
- Bioengineering
- Degree:
- Doctor of Philosophy
- Document Type:
- Dissertation
- Date of Defense:
- January 04, 2016
- Committee Members:
- Yong Wang, Dissertation Advisor/Co-Advisor
Yong Wang, Committee Chair/Co-Chair
Siyang Zheng, Committee Member
Peter J Butler, Committee Member
Na Xiong, Committee Member - Keywords:
- Hydrogel
aptamer
restriction endonuclease
cell adhesion
molecular reconfiguration
nondestructive cell release - Abstract:
- Materials with the capability of dynamically regulating cell adhesion hold potential for many biomedical applications, such as tissue engineering, regenerative medicine, cellular biology, and biological separation. These materials are usually created with polymers and ligands to achieve stable and specific cell-material interactions through ligand-receptor recognition. However, the strong and stable binding of cells on a material also poses a challenge to the subsequent release of the cells from the material in applications such as cell separation. To tackle this challenge, great efforts have been made in developing materials with the function of switching the cell binding state from adhesion to release responsive to different stimuli, such as pH, light, and temperature. However, most of these stimuli can cause detrimental effects on cells or even the death of cells. Therefore, it is important to create materials that can undergo changes in physiological conditions. Nucleic acid aptamers are an emerging class of ligands that bind cell receptors or soluble molecules with high affinity and specificity. In comparison to other ligands, they have various merits for the developments of cell attaching materials. Those merits include high affinity, low immunogenicity, and great stability. In addition, aptamers can be chemically modified for different conjugation chemistries. Importantly, the structure of aptamers can be programmed and tuned in physiological conditions. The purpose of this work was to synthesize aptamer-functionalized hydrogels for cell catch and release. It was hypothesized that aptamers conjugated hydrogels can induce cell catch on the hydrogel, and that the change of the chemical or physical status of the aptamers in physiological conditions can lead to cell release noninvasively. To test the hypothesis, two tasks were performed, including to develop aptamer-functionalized hydrogels and to examine its functions in chemical and physical changes. Chemical changes were achieved by using restriction endonuclease. Physical changes were achieved through DNA inter- and intra-molecular hybridization. These changes occurred in physiological conditions. The data show that target cells can be specifically captured on the aptamer-functionalized hydrogels, and more importantly that the cells can be released with high viability in physiological conditions. Thus, this work has successfully demonstrated a promising biomaterial for programmable cell catch and release in physiological conditions. The work described herein will make great contributions to the development of dynamic materials for controlling cell adhesion, thus improving diagnosis and therapy of a spectrum of diseases.