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

NIU, HONG
http://rave.ohiolink.edu/etdc/view?acc_num=osu1543406270126261

Abstract Details

2018, Doctor of Philosophy, Ohio State University, Materials Science and Engineering.
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.
Jianjun Guan (Advisor)
John Lannutti (Advisor)
W.S. Winston Ho (Committee Member)
336 p.
Materials Science; Polymers
multifunctional hydrogels; therapeutic angiogenesis; cell therapy; ischemic limb

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Citations

  • NIU, H. (2018). Functional Polymeric Hydrogels in Stem/Progenitor Cell Therapy and Therapeutic Angiogenesis [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1543406270126261

    APA Style (7th edition)

  • NIU, HONG. Functional Polymeric Hydrogels in Stem/Progenitor Cell Therapy and Therapeutic Angiogenesis. 2018. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1543406270126261.

    MLA Style (8th edition)

  • NIU, HONG. "Functional Polymeric Hydrogels in Stem/Progenitor Cell Therapy and Therapeutic Angiogenesis." Doctoral dissertation, Ohio State University, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=osu1543406270126261

    Chicago Manual of Style (17th edition)

osu1543406270126261
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This open access ETD is published by The Ohio State University and OhioLINK.