Development of semi-synthetic tissue using decellularized intestine and aptamer-functionalized hydrogel

Restricted
Author:
Zhang, Xiaolong
Graduate Program:
Bioengineering
Degree:
Doctor of Philosophy
Document Type:
Dissertation
Date of Defense:
September 04, 2015
Committee Members:
  • Yong Wang, Dissertation Advisor
  • Nanyin Zhang, Committee Chair
  • Siyang Zheng, Committee Member
  • Tak Sing Wong, Special Member
Keywords:
  • Decellularization; Aptamer; Hydrogel; Growth factor; Tissue rege
Abstract:
Decellularized tissues, derived from native tissues by removing cellular materials, retain the inherent architectural complexity of living tissues. They provide cells with an appropriate structural support for adhesion and proliferation and have been widely studied to restore, replace, or regenerate defective tissues in the field of regenerative medicine and tissue engineering. Despite the great potential, decellularized tissues lack bioactive growth factors due to the harsh decellularization procedure and therefore cannot provide cells with appropriate microenvironment for desirable tissue regeneration. Autograft is well accepted as the gold standard for tissue regeneration because it provides both physical (e.g., structure and mechanic) and chemical support (e.g., growth factors). To mimic autograft, a synthetic hydrogel that can sustainably release growth factors was integrated into decellularized tissue to create a semi-synthetic substitute. Because the semi-synthetic substitute can provide both physical and chemical support in tissue regeneration, it is expected to not only provide similar therapeutic outcomes as autograft, but also avoid the disadvantages of autograft, such as secondary surgery, limited material availability, and donor site morbidity. In this study, an aptamer functionalized gelatin-PEG hydrogel was incorporated into decellularized intestine to create a semi-synthetic skin substitute as a model. Three aims were proposed to synthesize and evaluate the semi-synthetic skin substitute. Aim 1 was to prepare and characterize the decellularized small intestine tissue. Aim 2 was to engineer an aptamer functionalized gelatin-PEG hydrogel and test the capability of the hydrogel in vascular endothelial growth factor (VEGF) sequestration and release. Aim 3 was to integrate the hydrogel with the decellularized intestine and examine the functions of the semi-synthetic skin substitute. The success of this study will lead to the synthesis of a biologically functional tissue substitute for tissue regeneration.