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Development of a Hydrogel Nanopartic...

Young, Daniel A.

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Development of a Hydrogel Nanoparticle System for Sustained Delivery of Anigogenic Factors for Therapeutic Neovascularization.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Development of a Hydrogel Nanoparticle System for Sustained Delivery of Anigogenic Factors for Therapeutic Neovascularization./
作者:	Young, Daniel A.
出版者:	Ann Arbor : ProQuest Dissertations & Theses, : 2018,
面頁冊數:	144 p.
附註:	Source: Dissertation Abstracts International, Volume: 79-11(E), Section: B.
Contained By:	Dissertation Abstracts International79-11B(E).
標題:	Biomedical engineering. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=10793875
ISBN:	9780438124615

Development of a Hydrogel Nanoparticle System for Sustained Delivery of Anigogenic Factors for Therapeutic Neovascularization.
Young, Daniel A.

Development of a Hydrogel Nanoparticle System for Sustained Delivery of Anigogenic Factors for Therapeutic Neovascularization. - Ann Arbor : ProQuest Dissertations & Theses, 2018 - 144 p.

Source: Dissertation Abstracts International, Volume: 79-11(E), Section: B.

Thesis (Ph.D.)--Illinois Institute of Technology, 2018.

Neovascularization requires controlled and sustained delivery of proangiogenic factors to stimulate reperfusion of ischemic tissues. Tissue engineering strategies for therapeutic neovascularization have used proangiogenic, recombinant growth factors to direct vessel development. Recently, peptides that mimic the bioactivity of growth factors have emerged as therapeutics for a variety of drug delivery applications, including therapeutic neovascularization. We designed hydrogel nanoparticles to provide sustained and tunable diffusion-based release of a proangiogenic peptide, QK, and a vessel stabilizing peptide, Vasculotide (VT). These nanoparticles were combined with a tissue engineering scaffold to promote tissue neovascularization. We used this nanocomposite system, utilizing peptide loaded hydrogel nanoparticles embedded in an implantable scaffold, to investigate the efficacy of a dual peptide delivery strategy for therapeutic neovascularization.

ISBN: 9780438124615Subjects--Topical Terms:

535387
Biomedical engineering.

Development of a Hydrogel Nanoparticle System for Sustained Delivery of Anigogenic Factors for Therapeutic Neovascularization.
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245 1 0 $a Development of a Hydrogel Nanoparticle System for Sustained Delivery of Anigogenic Factors for Therapeutic Neovascularization.
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500 $a Source: Dissertation Abstracts International, Volume: 79-11(E), Section: B.
500 $a Adviser: Georgia Papvasiliou.
502 $a Thesis (Ph.D.)--Illinois Institute of Technology, 2018.
520 $a Neovascularization requires controlled and sustained delivery of proangiogenic factors to stimulate reperfusion of ischemic tissues. Tissue engineering strategies for therapeutic neovascularization have used proangiogenic, recombinant growth factors to direct vessel development. Recently, peptides that mimic the bioactivity of growth factors have emerged as therapeutics for a variety of drug delivery applications, including therapeutic neovascularization. We designed hydrogel nanoparticles to provide sustained and tunable diffusion-based release of a proangiogenic peptide, QK, and a vessel stabilizing peptide, Vasculotide (VT). These nanoparticles were combined with a tissue engineering scaffold to promote tissue neovascularization. We used this nanocomposite system, utilizing peptide loaded hydrogel nanoparticles embedded in an implantable scaffold, to investigate the efficacy of a dual peptide delivery strategy for therapeutic neovascularization.
520 $a Inverse phase mini-emulsion polymerization (IPMP) was used to generate crosslinked poly(ethylene) glycol (PEG) hydrogel nanoparticles. We characterized the nanoparticles in terms of their swelling ratio, mesh size, surface charge (zeta-potential), and particle size distributions. We developed several nanoparticle formulations using various sizes and molar concentrations of PEG chains to study the effects of crosslink density on peptide release kinetics. This resulted in the formation of nanoparticles with low and high crosslink density as well as time-dependent variations in network density due to hydrolysis. We utilized two different loading techniques, peptide entrapment during IPMP and peptide post-loading into the nanoparticles, and found both to be effective via peptide loading measurements and release kinetic studies.
520 $a In the case of entrapment loading, peptides were included in the aqueous precursor during nanoparticle IPMP. Peptide release kinetics were tuned through adjustments in nanoparticle crosslink density. The resulting nanoparticle crosslink density impacted both peptide loading and fractional release, as studies showed higher crosslink density nanoparticles resulted in slower peptide release. The IPMP process preserved QK secondary structure and bioactivity, as confirmed with released peptide using circular dichroism spectroscopy and a Matrigel tubulogenesis assay, respectively.
520 $a In the case of the post-loading method, pristine nanoparticles were soaked in various concentrations of either QK or VT. Unlike with the entrapment loading method, crosslink density of the nanoparticles had little effect on release kinetics. However, much higher mass amounts of peptide could be loaded using this method and thus this method was chosen for the in vivo studies.
520 $a Next, we developed a hydrogel nanocomposite scaffold system to sequester nanoparticles for implantation. We characterized the nanocomposite scaffold system experimentally and theoretically using one-dimensional transport models of molecular diffusion. We estimated peptide diffusion coefficients from nanoparticles and the nanocomposites under perfect sink conditions. Importantly, we found this system capable of providing previously reported therapeutic thresholds of QK and VT.
520 $a Finally, the influence of sustained release of QK and VT on neovascularization was evaluated using a subcutaneous rat implant model. Results demonstrated statistically higher increases in perfused vessel density from peptide loaded nanocomposite scaffolds as compared to scaffolds where peptide was simply entrapped. These results suggest that controlled release of proangiogenic peptides from the developed nanoparticle system holds great potential for ischemic tissue repair.
590 $a School code: 0091.
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