Functional Polymeric Hydrogels in Stem/Progenitor Cell Therapy and Therapeutic Angiogenesis

Functional Polymeric Hydrogels in Stem/Progenitor Cell Therapy and Therapeutic Angiogenesis

Bibliographic Details
Main Author: NIU, HONG
Language:English
Published: The Ohio State University / OhioLINK 2018
Subjects:
Materials Science
Polymers
multifunctional hydrogels
therapeutic angiogenesis
cell therapy
ischemic limb
Online Access:http://rave.ohiolink.edu/etdc/view?acc_num=osu1543406270126261
id ndltd-OhioLink-oai-etd.ohiolink.edu-osu1543406270126261
record_format oai_dc
collection NDLTD
language English
sources NDLTD
topic Materials Science
Polymers
multifunctional hydrogels
therapeutic angiogenesis
cell therapy
ischemic limb
spellingShingle Materials Science
Polymers
multifunctional hydrogels
therapeutic angiogenesis
cell therapy
ischemic limb
NIU, HONG
Functional Polymeric Hydrogels in Stem/Progenitor Cell Therapy and Therapeutic Angiogenesis
author NIU, HONG
author_facet NIU, HONG
author_sort NIU, HONG
title Functional Polymeric Hydrogels in Stem/Progenitor Cell Therapy and Therapeutic Angiogenesis
title_short Functional Polymeric Hydrogels in Stem/Progenitor Cell Therapy and Therapeutic Angiogenesis
title_full Functional Polymeric Hydrogels in Stem/Progenitor Cell Therapy and Therapeutic Angiogenesis
title_fullStr Functional Polymeric Hydrogels in Stem/Progenitor Cell Therapy and Therapeutic Angiogenesis
title_full_unstemmed Functional Polymeric Hydrogels in Stem/Progenitor Cell Therapy and Therapeutic Angiogenesis
title_sort functional polymeric hydrogels in stem/progenitor cell therapy and therapeutic angiogenesis
publisher The Ohio State University / OhioLINK
publishDate 2018
url http://rave.ohiolink.edu/etdc/view?acc_num=osu1543406270126261
work_keys_str_mv AT niuhong functionalpolymerichydrogelsinstemprogenitorcelltherapyandtherapeuticangiogenesis
_version_ 1719454699224039424
spelling ndltd-OhioLink-oai-etd.ohiolink.edu-osu15434062701262612021-08-03T07:08:42Z Functional Polymeric Hydrogels in Stem/Progenitor Cell Therapy and Therapeutic Angiogenesis NIU, HONG Materials Science Polymers multifunctional hydrogels therapeutic angiogenesis cell therapy ischemic limb Stem/progenitor cell therapy is very promising for tissue regeneration. Yet the death of delivered cells due to ischemic conditions limits the application efficacy. Exploring approaches that both augment cell survival and monitor the tissue engineering process is clinically necessary for stem/progenitor cell therapy. In chapter 2, in vivo imaging enabled real-time visualization and monitoring of biomaterials in the field were investigated. Hypericin (HYP), which was found from plants of genus, was regarded as a natural photosensitizing and generally reported as a non-porphyrin photodynamic drug. However, the hydrophobicity and toxicity of HYP molecule make it difficult to administrate efficiently in vivo, which limits widespread clinical applications. In this study, we have developed a family of imageable and non-toxic hydrogel complexes by conjugating HYP molecules with injectable and thermosensitive hydrogels via the monomer of 1-Vinyl-2-pyrrolidinone (VP). The biocompatibility and efficacy of this new imageable system were examined in vitro and in vivo. The results demonstrated that these hydrogel complexes are attractive as cell carriers for photoimaging and photodiagnosis in vivo. In chapter 3, we developed thermosensitive NIPAAm-based hydrogels with high oxygen preservation as cell carriers to improve cell survival under ischemic conditions. The death of cells due to low oxygen and nutrient environment is the major limitation for therapeutic efficacy. The P_(O_2 ) is around 30-40 mm Hg in subcutaneous tissue, which is the lowermost layer of the integumentary system. However, the oxygen level drops to under 30 mm Hg under hypoxic condition. In order to overcome the hypoxia, one strategy is to deliver oxygen via polymeric biomaterials with oxygen generators for wound healing. The developed hydrogels exhibited fast gelation rates, injectability and high oxygen preservation. With these attractive properties, the hydrogels can be used as cell carriers, providing mechanical support and protection for tissue regeneration. Another characteristic of tissue ischemia is the overproduction of reactive oxygen species (ROS) that compromises cell survival. In other words, protecting cells from ROS attack may improve cell survival. Moreover, one of the major limitations of delivering stem cells into ischemic tissues is low cell retention. To mitigate these problems, we developed ROS-sensitive hydrogels to protect the encapsulated cells in chapter 4. For therapeutic angiogenesis, the endothelial cell can respond and release mediators to affect the cardiac modeling. Recent studies indicate that TGF-ß ligands treated endothelial cells exhibit decreased proliferation, migration and angiogenesis. Therefore, inhibiting TGFß signaling pathway has attracted increasing interest in effective angiogenesis. The work in chapter 5 through 6 aims (1) to develop a TGFß Receptor II binding peptide (ECG) that can inhibit the signaling pathway to promote angiogenesis, (2) to synthesize a drug carrier to encapsulate ECG and bFGF for long-term release, (3) to apply the delivery system in vivo using mice of ischemic limb model to investigate its efficacy. The results showed that in vitro, ECG/bFGF significantly promoted cell migration and proliferation. In vivo, the delivery system ultimately improved the blood vessel density. In addition, a triple delivery system of MSCs/bFGF/ECG was developed, which further enhanced therapeutic angiogenesis and promoted tissue regeneration. Moreover, the vessel branching in the angiogenesis and arteriogenesis was studied by Dll4/VEGF encapsulated in ROS sensitive hydrogels, showing potential in improving muscle repair by stimulating the growth of filopodial structure of endothelial cells both in vitro and in vivo. 2018 English text The Ohio State University / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=osu1543406270126261 http://rave.ohiolink.edu/etdc/view?acc_num=osu1543406270126261 restricted--full text unavailable until 2023-12-17 This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws.

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